Characterizing the Process of Urgent Referrals and Transfers to a Large Tertiary Care Apheresis Centre in Ontario

Background: Therapeutic plasma exchange (TPE) and red blood cell exchange (RBCX) are potentially life-saving treatments. Given the specialized nature of care, apheresis is only offered in 7 centres in Ontario (population: 14.5 million), and therefore effectively functions as a provincial service. Patients can be referred to any apheresis centre, regardless of home local health integration network (LHIN). Referrals are directed by CritiCall Ontario (CritiCall), a 24/7 consultation and referral service funded by the Ontario Ministry of Health and Long-Term Care (MOHLTC). CritiCall facilitates the MOHLTC Life or Limb Policy, which provides that patients with life or limb threatening conditions will receive timely consultation, and if necessary, transfer to an appropriate centre within a best effort window of 4 hours. We used CritiCall data to examine referral, acceptance, and transfer processes of urgent TPE and RBCX apheresis calls to our centre. Methods: Time and process data for all CritiCall transfers to our centre for TPE and RBCX between October 2013 and December 2018 were included. TPE cases were analyzed if transferred for codes related to thrombotic thrombocytopenic purpura (TTP) or other thrombotic microangiopathies, and RBCX cases were analyzed only for acute sickle cell indications (e.g. stroke, acute chest syndrome). As such, we assumed all transfers to be "life or limb." Continuous variables were analyzed by linear regression. Categorical variables were analyzed using nonparametric tests. Data were provided in accordance with the Personal Health Information Protection Act, 2004 (www.criticall.org/Article/Privacy). Results: A total of 69 cases (43 TPE, 26 RBCX) were included. Median patient age was 51 (IQR 37) years for TPE and 29 (IQR 16) for RBCX. Most patients (61%) were female. Total time from referral to patient arrival at our centre was 243 (IQR 168) minutes. The greatest proportion of this total was from patient acceptance to arrival (169 [IQR 108] minutes), whereas time from referral to contact with the physician, and time from contact to patient acceptance were 23 (IQR 53) and 12 (IQR 41) minutes, respectively. The life or limb benchmark was met in 74% of cases, assessing time between acceptance and arrival. Fifty-two percent of the patients were accepted by the first apheresis physician contacted, with an average of 3 physicians contacted before a patient was accepted. Distance between referring and accepting centres was 39 (IQR 39) kilometres, and ground transportation was used most often. A minority of cases (7%) transferred were within our own LHIN. Multiple linear regression examining factors that contribute to total time from referral to arrival demonstrated that distance was independently associated with total time (p<0.001). Transfers took an additional 6.7 minutes for every 10 km between the referring and accepting centres. Male sex was also independently associated with total time (p=0.041), with 55 additional minutes required per transfer of male patients compared to female. Transfer time was not significantly associated with age, procedure (TPE vs. RBCX), mode of transport, number of centres contacted, or within-LHIN referral. Conclusions: We have described the processes of urgent apheresis referrals to our centre. The 4 hour "life or limb" benchmark was met in just under 75% of transfers, with the greatest delay occurring between patient acceptance and arrival. This is important given that time to initiate treatment is associated with better outcomes. Distance between centres is an important factor and potential target for improvement. Our analysis shows that >90% of cases were from outside our LHIN, reflecting a truly provincial catchment. Quality improvement strategies should be aimed at pairing referrals with nearest apheresis centres, and creating efficiency in the interval between patient acceptance and arrival. It is unclear from these data why male sex is associated with longer transfer times, but it is a target for further analysis. There are limitations of this analysis: data were not available for cases that were not ultimately transferred, nor for transfers to other centres. Future work will include examining patterns of province-wide transfers, as well as including blood bank data to further characterize steps involved in initiating aphaeresis. Acknowledgements: We thank M. Shaikh, J. Dempsey, M. Gavel at CritiCall for their contributions. Disclosures Kuo: Pfizer: Consultancy, Research Funding; Celgene: Consultancy; Apellis: Consultancy; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Bluebird Bio: Consultancy; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees. Patriquin:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Predictors of Maternal Morbidity Among Participants Enrolled in the Sickle Cell Disease Implementation Consortium Registry

Blood ◽

10.1182/blood-2020-140743 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 3-3

Author(s):

Rita V Masese ◽

Dominique Bulgin ◽

Liliana Preiss ◽

Mitchell Knisely ◽

Eleanor Stevenson ◽

...

Keyword(s):

Board Of Directors ◽

Sickle Cell ◽

Research Funding ◽

Transfusion Requirement ◽

The United States ◽

Acute Chest Syndrome ◽

Maternal Outcomes ◽

Maternal Complications ◽

Advisory Committees ◽

Increased Risk

Introduction Pregnancy in sickle cell disease (SCD) is associated with an exacerbation of SCD-related complications and an increased risk of maternal complications. The increased risk is partly due to physiologic adaptations in pregnancy, which include increased metabolic demands and a hypercoagulable state. The maternal death rate for SCD is 629 per 100,000 deliveries, compared to 12 per 100,000 deliveries in black women and 6 per 100,000 deliveries in the general population (Raider et al., 2016). Studies on maternal and perinatal outcomes of patients with SCD present inconsistent and conflicting results. Some studies have reported an increase in maternal complications such as pre-eclampsia, acute chest syndrome and thromboembolic events, while other studies have reported no significant risk in adverse maternal outcomes. The inconsistent findings reported in prior studies may be attributed to small sample sizes and single-centered sites. Our study aims to determine the prevalence and predictors of maternal morbidity among participants enrolled in the SCD Implementation Consortium (SCDIC) registry, which is the largest, most geographically diverse SCD participant sample in the United States. Methods This cross-sectional study included women enrolled in the SCDIC registry who had at least one pregnancy event. The SCDIC is composed of eight academic SCD centers across the United States and one data-coordinating center. Participants were enrolled in the SCDIC registry if they were 18 to 45 years of age and had a confirmed diagnosis of SCD. Enrolled participants completed a series of surveys that collected sociodemographic information, SCD and pregnancy history and data abstractions of participants' medical records was completed. Medical complications queried during pregnancy included: vaso-occlusive episodes, acute chest syndrome, blood transfusion requirement, preeclampsia, maternal diabetes and deep venous thrombosis. Descriptive analysis of sociodemographic, clinical and maternal characteristics was conducted. Bivariate analysis was performed using Chi-Square test, Mann-Whitney U test, t-test, and logistic regressions, as appropriate. A p-value of ≤ 0.05 was considered statistically significant for all analysis. Results The study sample included 743 women who had at least one pregnancy event, and a total of 1066 live births. Almost all women (96.3%) were African American, with a median age of 21 years (inter-quartile range of 19 to 23 years) at first birth. The majority had Hb SS SCD genotype (69.5%; 513 of the 738 with SCD genotype data). Of all reported pregnancies, participants did not use hydroxyurea during conception (78%), and pregnancy (84.5%). Only 2.7 % of the women reported using fertility drugs or assisted reproductive procedures. Seventy five percent of the pregnancies that ended in live births had maternal complications. The leading complications were vaso-occlusive episodes (61.2%), pregnancy requiring blood transfusion(s) (33.2%), preeclampsia (15.4%), deep venous thrombosis (5.6%) and acute chest syndrome (7.7%). When the pregnancies were stratified by SCD genotype, women with Hb SS had a higher occurrence of acute chest syndrome (63.4% vs. 26.7%), transfusion requirement (70.8% vs. 21%) and preeclampsia (66.7% vs 22.4%). In the univariate logistic regressions, multiparous women, with a history of adverse maternal outcomes in a previous pregnancy, had higher odds of vaso-occlusive episodes (OR: 3.42; 95% CI: 2.42-4.94) acute chest syndrome (OR:4.99; 95% CI:2.56- 9.48), transfusion requirement (OR:3.86; 95% CI:2.64- 5.69), and pre-eclampsia (OR:3.36; 95% CI:2.05-5.45). Conclusion In this large multicenter registry, we found pregnant women with SCD have significant maternal complications. Early antenatal care by healthcare providers knowledgeable about risk factors for adverse maternal outcomes in SCD is essential improve maternal and fetal outcomes and reduce the maternal death rate for SCD. Disclosures Hankins: Novartis: Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; MJH Life Sciences: Consultancy, Patents & Royalties; UptoDate: Consultancy; National Heart, Lung, and Blood Institute: Honoraria, Research Funding; LINKS Incorporate Foundation: Research Funding; American Society of Pediatric Hematology/Oncology: Honoraria. Treadwell:Global Blood Therapeutics: Consultancy; UpToDate: Honoraria. King:Amphivena Therapeutics: Research Funding; Bioline: Consultancy; Celgene: Consultancy; Cell Works: Consultancy; Incyte: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novimmune: Research Funding; RiverVest: Consultancy; Tioma Therapuetics: Consultancy; WUGEN: Current equity holder in private company. Gordeuk:CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Imara: Research Funding; Ironwood: Research Funding; Novartis: Consultancy. Kanter:SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; AGIOS: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; GLG: Honoraria; Jeffries: Honoraria; Cowen: Honoraria; Wells Fargo: Honoraria; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; Medscape: Honoraria; Guidepoint Global: Honoraria; bluebird bio, inc: Consultancy, Honoraria; Sanofi: Consultancy. Glassberg:Pfizer: Research Funding; Global Blood Therapeutics: Consultancy; Eli Lilly and Company: Research Funding. Shah:Novartis: Consultancy, Research Funding, Speakers Bureau; Alexion: Speakers Bureau; CSL Behring: Consultancy; Bluebird Bio: Consultancy; Global Blood Therapeutics: Consultancy, Research Funding, Speakers Bureau.

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Efficacy of Ruxolitinib By Baseline Spleen Volume in Patients with Polycythemia Vera Resistant to or Intolerant of Hydroxyurea

Blood ◽

10.1182/blood.v124.21.1840.1840 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1840-1840 ◽

Cited By ~ 1

Author(s):

Alessandro M. Vannucchi ◽

Srdan Verstovsek ◽

Mark M Jones ◽

Shui He ◽

Jingjin Li ◽

...

Keyword(s):

Logistic Regression ◽

Linear Regression ◽

Polycythemia Vera ◽

Board Of Directors ◽

Research Funding ◽

Spleen Volume ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership ◽

Response Trial

Abstract Background : Polycythemia vera (PV) is a myeloproliferative neoplasm defined by erythrocytosis; patients may also have increased platelets and white blood cells as well as splenomegaly and disease-related symptoms. JAK/STAT activation is the primary driver of PV pathogenesis, in most cases resulting from the JAK2V617F mutation. The RESPONSE trial compared ruxolitinib (RUX) and best available therapy (BAT) in patients with PV and splenomegaly who were intolerant of or resistant to hydroxyurea (HU) according to modified European LeukemiaNet criteria. At the time of the primary analysis, RUX demonstrated superior improvements in hematocrit (HCT) control, symptom burden, and spleen volume compared with BAT. This post hoc analysis of RESPONSE was conducted to determine if treatment outcomes were influenced by baseline spleen volume. Methods : Patients with PV ≥18 years of age who were resistant to or intolerant of HU with palpable spleen (confirmed by MRI/CT to be ≥450 cm3) and phlebotomy requirement were randomized 1:1 to receive open-label RUX 10 mg BID or BAT. The primary endpoint was a composite that required a ≥35% reduction in spleen volume at Week 32 and hematocrit (HCT) control. HCT control was defined as lack of phlebotomy eligibility (based on HCT values) between Weeks 8–32 with no more than 1 phlebotomy eligibility between randomization and Week 8. A linear regression was conducted to determine the effect of baseline spleen volume on the percent change in spleen volume at Week 32. A logistic regression was conducted to determine the effect of baseline spleen volume on HCT control through Week 32. Spleen volume was measured by MRI at screening and Weeks 16 and 32. Hematocrit was assessed at screening, prerandomization, and every 2 weeks from Day 1 to Week 12, followed by every 4 weeks until Week 32. Results :The RESPONSE trial enrolled 222 patients (RUX, 110; BAT, 112). Median (range) spleen volume at baseline was 1195 cm3 (396–4631 cm3) in the RUX arm and 1322 cm3 (254–5147 cm3) in the BAT arm. Baseline median (range) spleen length by palpation was 7.0 cm (0.0–24.0 cm) in the RUX arm and 7.0 cm (0.0–25.0 cm) in the BAT arm. In the 24 weeks prior to screening, most patients in both arms had ≥2 phlebotomy procedures (RUX, 87%; BAT, 80%). There was no correlation between the percentage change in spleen volume at Week 32 and baseline spleen volume; linear regression showed no significant effect of baseline spleen volume on the percentage change in spleen volume at Week 32 (P=0.40). No significant effect of baseline spleen volume on HCT control through Week 32 was identified based on logistic regression analysis (P=0.37). Conclusion : In PV patients with inadequate response to or intolerant of HU, the degree of splenomegaly at baseline did not influence achievement of HCT control or reduction in spleen volume with RUX therapy. Disclosures Vannucchi: Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: Ruxolitinib is a JAK1/JAK2 inhibitor approved for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Verstovsek:Incyte Corporation: Research Funding. Jones:Incyte Corporation: Employment, Equity Ownership. He:Incyte Corporation: Employment, Equity Ownership. Li:Novartis Pharmaceuticals: Employment, Equity Ownership. Habr:Novartis Pharmaceuticals: Employment, Equity Ownership. Kiladjian:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Serum TARC Concentration Kinetic in Classical Hodgkin Lymphoma during First-Line Treatment

Blood ◽

10.1182/blood-2021-148137 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4500-4500

Author(s):

Ilaria Romano ◽

Benedetta Puccini ◽

Leonardo Signori ◽

Michela Zizza ◽

Giacomo Coltro ◽

...

Keyword(s):

Treatment Response ◽

Board Of Directors ◽

Stage I ◽

Stage Ii ◽

Categorical Variables ◽

Line Treatment ◽

First Line ◽

Advisory Committees ◽

Significant Difference ◽

First Line Treatment

Abstract Introduction: Thymus and activation-regulated chemokine (TARC) has been recently identified as a promising predictor of response in patients (pts) with classical Hodgkin's Lymphoma (HL). A correlation between treatment response and early sTARC reduction in HL pts treated with PET-adapted strategy was reported (Guidetti A, Leuk Res, 2017; Viviani S, Hematol Oncol, 2020). In the current study, we analyzed the kinetic of sTARC in HL pts during first-line treatment, with the aim to evaluate its potential predictive value. Methods: We prospectively collected plasma samples of naïve HL pts. Pts were stratified according to GHSG risk categories. Localized HL were treated with 2-4 cycles of ABVD followed by involved field radiotherapy (IFRT); advanced HL underwent 6 cycles of ABVD. Pts with a positive PET-2 switched to an intensification treatment. Pts with positive end of treatment PET (EOT-PET) were treated with BeGEV followed by autologous stem cell transplantation (ASCT). sTARC levels were measured with a commercial TARC ELISA kit (R & D Systems, Minneapolis, US) according to manufactory instructions. Samples were collected immediately before treatment on day 1 of each ABVD cycle, before IFRT in localized stages, on day 1 of each cycle of salvage therapy, including ASCT, and 1 month after EOT. Samples were analyzed in duplicate. Statistical analysis was performed using IBM SPSS Statistic v.27 and GraphPad PRISM v.8; Continuous variables were compared by Mann-Whitney U test, categorical variables by χ 2 test. Statistical significance was defined as P=.05. Results: Of 43 pts enrolled in the study, 4 pts were excluded due to missing samples, and for 3 PET-2 positive pts data were unavailable at time of this analysis; overall evaluable pts were 36. Median age was 33.5 yr (range 17−65), 58% pts were male. B-symptoms were present in 50% of pts. Fourteen pts (39%) were early stage (IA, IB, IIA), 22 pts (61%) were advanced stage (IIB, III, IV). Four pts (11%) were refractory, documented by EOT-PET positivity. For the purposes of this analysis, pts were stratified in two subgroups including stage I pts (11%) and stage II-IV (89%). Median baseline sTARC was 35,454 pg/ml (range 273−183,225); levels were significantly lower in stage I compared to stages II-IV (524 vs 50,606 pg/ml, P=.001). Median sTARC after 2 ABVD cycles (sTARC-2) was 482 pg/ml (range 97−2,071) in the whole population, with a median logarithmic reduction (logRED) vs baseline of 1.83 (range -0.26−3.12). In stage II-IV a significant decrease of sTARC-2 (median 493 pg/ml; range 97−2,071), with a median logRED of 1.94 (range 0.73−3.12), was observed, unlike in stage I where sTARC-2 remained stable (median 393 pg/ml; range 279−805); median logRED -0.03 (range -0.27 to 0.57) (Fig 1A). We then compared sTARC in chemorefractory and chemosensitive stage II-IV pts. We observed an almost significant difference (P=.077) by considering baseline sTARC in the two groups, respectively 95,236 pg/ml (range 53,502−135,787) in chemorefractory and 35,454 pg/ml (range 5,475−183,225) in chemosensitive pts. However, sTARC-2 and the logRED of sTARC-2 were not significantly different between the two groups: 654 pg/ml (range 97−1,564) vs 463 (range 150−2,071) and 2.1 (range 1.6−3.1) vs 2.0 (range -0.7−2.6), respectively. Finally, sTARC measurements after PET-2 and before EOT-PET, and their log variation (logΔ) as compared to sTARC-2, were assessed in chemorefractory and chemosensitive subgroups. In refractory pts, a progressive increase of sTARC was observed: median sTARC was 32,202 pg/ml (range 14,362−71,807) at the time of biohumoral relapse compared to 373 pg/ml (range 166−1,102) in responding pts (P=.001). The corresponding log∆ values were -1.5 (range -2.9 to -1.1) and 0.1 (range -0.3−0.6) (P=.001), respectively (Fig 2B). Conclusions: The current study, with the limitations of small pts number, provides an analysis of sTARC prognostic implications in pts with HL. While sTARC is of limited value in pts with stage I disease, the kinetic of sTARC variation in pts with stage II-IV HL resulted well correlated with treatment response as assessed by EOT-PET. Specifically, an increase of sTARC during treatment after sTARC-2 may predict refractoriness at later cycles. Larger studies are needed to confirm that monitoring of sTARC in stage II-IV HL during treatment might provide prognostic and therapeutic insights. Supported by Legato Zottola, University of Florence Figure 1 Figure 1. Disclosures Puccini: Takeda: Membership on an entity's Board of Directors or advisory committees. Vannucchi: BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees. Nassi: Incyte: Consultancy; Takeda: Consultancy; Roche: Consultancy; Kyowa Kirin: Consultancy.

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Sex Based Differences in Sickle Cell Disease

Blood ◽

10.1182/blood-2020-140896 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 37-37

Author(s):

Rita V Masese ◽

Dominique Bulgin ◽

Mitchell Knisely ◽

Liliana Preiss ◽

Eleanor Stevenson ◽

...

Keyword(s):

Sickle Cell Disease ◽

Board Of Directors ◽

Sickle Cell ◽

Research Funding ◽

Categorical Variables ◽

Continuous Variables ◽

Cell Disease ◽

Advisory Committees ◽

Blood Institute ◽

National Heart Lung

Introduction Sickle cell disease (SCD) is the most common inherited blood disorders in the United States. The disease predominantly affects African Americans with 1 out of every 365 individuals born with SCD. The disease is characterized by vascular inflammation and vaso-occlusion leading to numerous complications and multi-organ dysfunction. Previous studies have shown women with SCD tend to outlive their male counterparts. Other than the increased life expectancy, sex-based clinical outcome differences in SCD remain largely unknown. To better characterize sex-based differences in SCD, we assessed sociodemographic characteristics, pain, treatment characteristics, laboratory measures and complications among males and females currently enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. Methods The SCDIC consists of eight academic and comprehensive SCD centers, and one data-coordinating center that received funding from the National Heart Lung and Blood Institute to improve outcomes for individuals with SCD. Participants were eligible for the enrollment in the SCDIC registry if they were 15 to 45 years of age and had a confirmed diagnosis of SCD. Participants were excluded if they had sickle cell trait or had a successful bone marrow transplant. Enrolled participants completed surveys. Data were also abstracted from the participants' medical records. Data were entered into a REDCap database and analyzed using SAS version 9.4 (SAS Institute; Cary, NC). Categorical variables were presented as frequencies and percentages, continuous variables were presented as medians and interquartile ranges (IQR) or means and standard deviations. Categorical variables were analyzed using Chi-Square or Fisher exact tests when appropriate. Continuous variables were compared using the Mann-Whitney U test or independent sample t-tests depending on the distribution. A two-sided p-value less than 0.05 was deemed significant. Results A total of 2,124 participants were included in the study. The mean (SD) age of our participants was 27.8 (7.9) years. Almost all (95.6%) were Africa American, female (56%) and had hemoglobin SS (68.2%) SCD genotype. More males (55.4 % vs. 44.6%, p <0.0001) were taking hydroxyurea. Females had significantly worse reports of pain frequency and severity (p=0.0002 and <0.0001 respectively), more vaso-occlusive episodes (p=0.01) and a higher occurrence of 3 or more hospital admissions in the past year (30.9 % vs. 25.5, p= 0.03). Males had significantly more skin ulcers and respiratory, musculoskeletal, genitourinary and cardiovascular complications while females had more anxiety, depression and autoimmune conditions. Males also had significantly higher creatinine, blood urea nitrogen, albumin and liver enzymes (alkaline phosphatase, aspartate and alanine aminotransferases). Females had higher fetal hemoglobin levels with and without hydroxyurea use. There were no statistical differences in ethnicity, marital and employment status. Conclusion Key differences in SCD presentation and occurrence of complications exist among males and females. Females had higher rates of depression and anxiety while males had more chronic end-organ complications that are life threatening. Our findings emphasize the need for stratification of data analysis by sex in future SCD studies. Disclosures Hankins: Global Blood Therapeutics: Consultancy, Research Funding; National Heart, Lung, and Blood Institute: Honoraria, Research Funding; LINKS Incorporate Foundation: Research Funding; American Society of Pediatric Hematology/Oncology: Honoraria; MJH Life Sciences: Consultancy, Patents & Royalties; UptoDate: Consultancy; Novartis: Research Funding. Treadwell:UpToDate: Honoraria; Global Blood Therapeutics: Consultancy. King:Tioma Therapuetics: Consultancy; WUGEN: Current equity holder in private company; RiverVest: Consultancy; Celgene: Consultancy; Cell Works: Consultancy; Incyte: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bioline: Consultancy; Novimmune: Research Funding; Amphivena Therapeutics: Research Funding. Gordeuk:CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Imara: Research Funding; Ironwood: Research Funding; Novartis: Consultancy. Kanter:bluebird bio, inc: Consultancy, Honoraria; SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; AGIOS: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Sanofi: Consultancy; Medscape: Honoraria; Guidepoint Global: Honoraria; GLG: Honoraria; Jeffries: Honoraria; Cowen: Honoraria; Wells Fargo: Honoraria; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees. Glassberg:Eli Lilly and Company: Research Funding; Pfizer: Research Funding; Global Blood Therapeutics: Consultancy. Shah:Bluebird Bio: Consultancy; Novartis: Consultancy, Research Funding, Speakers Bureau; Global Blood Therapeutics: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy; Alexion: Speakers Bureau.

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Benefits of a Disease Management Program for SCD in Germany 2011 - 2019: The Increased Use of Hydroxyurea Correlates with a Reduced Frequency of Acute Chest Syndrome

Blood ◽

10.1182/blood-2021-148550 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 973-973

Author(s):

Joachim B. Kunz ◽

Andreas Schlotmann ◽

Andrea Daubenbüchel ◽

Stephan Lobitz ◽

Andrea Jarisch ◽

...

Keyword(s):

Disease Management ◽

Board Of Directors ◽

Disease Management Program ◽

Treatment Guidelines ◽

Management Program ◽

Acute Chest Syndrome ◽

Insurance Company ◽

Advisory Committees ◽

Defined Daily Doses ◽

Number Of Patients

Abstract Background Worldwide, Sickle Cell Disease (SCD) is the most common single gene disorder affecting >250,000 newborns annually. In Germany, SCD qualifies as a rare disease and almost exclusively affects immigrants from endemic countries and their descendants. The recent surge of immigration from high-prevalence countries increased the numbers of patients with SCD in Germany and raised awareness for the need of specialized care. In 2012, the German Society for Pediatric Oncology and Hematology (GPOH) mandated a consortium of five university hospitals to develop a disease management program for patients with SCD. This consortium issued treatment guidelines for SCD that strongly favor the use of hydroxyurea, initiated patient and physician education events, prepared for a universal newborn screening program that will start 09/2021, moderated a consensus on the indication of allogeneic stem cell transplantation for patients with SCD, and established a national patient registry. Methods In order to quantify the effect of these activities, we made use of claims data that were collected by the research institute (WIdO) of the major German insurance company, the Allgemeine Ortskrankenkasse (AOK), and of publicly accessible data collected by the Federal Statistical Office (Statistisches Bundesamt, Destatis). ICD10 codes were used to identify patients with SCD and their comorbidities. Pharmacologic treatments were quantified using the German Anatomical Therapeutic Chemical (ATC)-Classification with defined daily doses. Results We estimate that the number of patients with SCD in Germany increased from approximately 2,200 in 2011 to approximately 3,200 in 2019. Analyses of administered treatments illustrate that important components of recently issued national treatment guidelines have been largely implemented. Specifically, the use of hydroxyurea has more than doubled, resulting in a proportion of approximately 45% of all patients with SCD being treated with hydroxyurea in 2019 (Figure 1A). In strong negative correlation with the use of hydroxyurea, the frequency of acute chest syndromes decreased (Figure 1B). While before the widespread use of hydroxyurea (2011-2013) 8.1% of patients with SCD were admitted at least once per year for ACS, this proportion dropped to 6.6% in the period 2017 to 2019. Similarly, the proportion of patients who required analgesics, red blood cell transfusions and hospitals admissions declined from 2011 to 2019, indicating a reduced burden of SCD with the increased use of hydroxyurea. Conclusion In sum, these data demonstrate an association between the dissemination of nationwide treatment guidelines and changes in clinical practice in particular relating to the use of hydroxyurea. These changes translate into a remarkable improvement of key measures of disease activity in a representative population based analysis. Figure 1 Figure 1. Disclosures Lobitz: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; AddMedica: Honoraria, Membership on an entity's Board of Directors or advisory committees; Vertex: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kulozik: BioMedX: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria; bluebird bio, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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Allogeneic Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia with Post-Transplantation Cyclophosphamide: Assessing the Importance of Conditioning Regimen, Donor Choice, and Tyrosine Kinase Inhibitor Use

Blood ◽

10.1182/blood-2020-141294 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 44-45

Author(s):

Jonathan Webster ◽

Leo Luznik ◽

Hua-Ling Tsai ◽

Philip H. Imus ◽

Amy E. DeZern ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Conditioning Regimen ◽

Advisory Board ◽

Categorical Variables ◽

Advisory Committees ◽

Post Transplant ◽

Scientific Advisory Board ◽

Scientific Advisory ◽

Donor Type

Background: Contemporary trials in adult Ph+ ALL patients with TKIs continue to show improved outcomes with allogeneic blood or marrow transplantation (alloBMT) in first remission (CR1) (Chalandon. Blood. 2015 AND Ravandi. Blood Adv. 2016). These studies have relied on myeloablative conditioning (MAC) and largely required an HLA-matched donor. Post-transplant survival in Ph+ ALL has been shown to be similar between patients transplanted with reduced-intensity conditioning (RIC) and MAC, but the incidence of relapse after RIC is higher (Bachanova. Leukemia. 2014). Post-transplant TKI maintenance reduces the incidence of relapse (Brissot. Haematologica. 2015), but this strategy has not specifically been investigated after RIC. Additionally, HLA-haploidentical donor transplants using post-transplant cyclophosphamide (PTCy) as a component of graft-versus-host disease (GVHD) prophylaxis have comparable outcomes to HLA-matched transplants (McCurdy. Haematologica. 2017). We analyzed outcomes among patients who universally received PTCy and attempted post-transplant TKI prophylaxis to determine the importance of remission status (CR1 vs. later), conditioning regimen, donor type, and TKI choice. Methods: The bone marrow transplant database at Johns Hopkins was queried for adult patients with de novo Ph+ ALL who received alloBMT using PTCy between January 2008 and August 2018. Characteristics of patients were summarized and compared using the student's T test for continuous variables and Fisher's exact test for categorical variables. Estimators of OS and RFS were reported using the Kaplan-Meier method. Differences in time-to-event outcomes were estimated using Cox proportional hazards model. Results: A total of 81 transplants for Ph+ ALL were performed: 69 (85%) in CR1 and 12 (15%) in second or greater remission (CR2+). The demographics are presented in Table 1 and separated by conditioning regimen [MAC vs. nonmyeloablative (NMAC)] for transplants in CR1. The cumulative incidences of grade 2-4 and grade 3-4 aGVHD at 1 year were 33% (95% CI, 23% to 44%) and 9% (95% CI, 3% to 15%), respectively. The incidence of moderate or severe cGVHD at 2 years was 8% (95% CI, 2% to 13%). Nearly all patients (91.4%) initiated a post-transplant TKI at a median of 56 days. Overall, 44.4% of patients were able to take a TKI on ≥85% of nonrelapse days from day 31-395 post-transplant. AlloBMT in CR1 (compared to CR2+) improved RFS (HR=0.25, p=0.0002) and pre-transplant minimal residual disease (MRD) by flow cytometry (MFC) was associated with decreased RFS (HR=2.57, p=0.039). The presence of pre-transplant MRD by PCR did not confer an increased risk of relapse (HR 1.12, p=0.84). Among the 69 patients transplanted in CR1, the 5-year OS was 77.6% (95% CI, 64.8% to 86.2%) and RFS was 67% (95% CI, 52.4-76.5%). As shown in Figure 1, the use of NMAC versus MAC (HR 0.37, p=0.02) and dasatinib versus imatinib at diagnosis (HR 0.21, p=0.007) led to improved relapse-free survival (RFS) in univariate analyses. Neither donor type (with the majority being haploidentical) nor recipient age ≥60 affected RFS. Post-transplant TKI prophylaxis was discontinued prior to relapse in 20 patients among whom 12 remain in an MRD-negative remission, 4 died of non-relapse causes, 3 relapsed, and 1 developed recurrent MRD controlled by a TKI. The median duration of post-transplant TKI prophylaxis prior to discontinuation was 46.5 months in those who remain in treatment-free remission versus 15.6 months in those who relapsed (p=0.01). Eighteen relapses occurred on maintenance therapy, and 90% of tested cases were positive for a kinase domain mutation conferring resistance to the TKI in use at relapse. No significant difference in the median time to TKI initiation post-transplant was noted between those who relapsed on maintenance and those who did not (70 days vs. 55 days, p=0.6). All patients in ongoing remission were MRD-negative by PCR at their most recent evaluation. Conclusions: AlloBMT with PTCy in Ph+ ALL was most effective when performed in CR1 with negative MFC for MRD. The initiation of post-transplant TKI prophylaxis was nearly universal. Among patients transplanted in CR1, the best results were achieved in patients treated with dasatinib at diagnosis (5-year RFS 83%) and NMAC (5-year RFS 73.1%). Thus post-transplant TKI prophylaxis appeared to overcome any relapse control advantage for MAC, yielding better outcomes with NMAC. Disclosures Webster: Amgen: Consultancy; Pfizer: Consultancy. Luznik:WindMil Therapeutics: Patents & Royalties: Patent holder; Genentech: Research Funding; Merck: Research Funding, Speakers Bureau; AbbVie: Consultancy. DeZern:Abbvie: Consultancy; Astex: Research Funding; MEI: Consultancy; Celgene: Consultancy, Honoraria. Pratz:Jazz Pharmaceutical: Consultancy; Millennium: Research Funding; Daiichi Sankyo: Research Funding; Agios: Other: Scientific Advisory Board, Research Funding; Celgene: Other: Scientific Advisory Board; Boston BioMedical: Consultancy; Astellas: Other: Scientific Advisory Board, Research Funding; AbbVie: Other: Scientific Advisory Board, Research Funding. Levis:Astellas: Honoraria, Research Funding; Menarini: Honoraria; Amgen: Honoraria; FujiFilm: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria. Gojo:Amgen: Research Funding; Merck: Research Funding; Genentech: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Amphivena: Research Funding. Bolanos-Meade:Incyte: Other: DSMB Fees. Dalton:Eli Lilly: Research Funding; AbbVie: Research Funding. Jain:Takeda: Consultancy, Honoraria; Bristol Myer Squibb: Other: for advisory board participation; CareDx: Other: Advisory Board. Ali:Celgene: Membership on an entity's Board of Directors or advisory committees. Borrello:Celgene: Research Funding; Aduro: Patents & Royalties; WindMIL Therapeutics: Other: Founder , Research Funding. Wagner-Johnston:ADC Therapeutics, Regeneron, CALIB-R, Verastem: Membership on an entity's Board of Directors or advisory committees. Smith:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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Real-World Outcomes with Bortezomib-Containing Regimens and Lenalidomide Plus Dexamethasone for the Treatment of Transplant Ineligible MM Patients: A Multi-Institutional Report from the National Myeloma Canada Research Network (MCRN) Database

Blood ◽

10.1182/blood-2018-99-117363 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2008-2008 ◽

Cited By ~ 1

Author(s):

Victor Jimenez-Zepeda ◽

Donna E Reece ◽

McCurdy R Arleigh ◽

Esther Masih-Khan ◽

Eshetu G Atenafu ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Real World ◽

Research Funding ◽

Small Sample ◽

Research Network ◽

National Database ◽

Categorical Variables ◽

Advisory Committees ◽

Entire Cohort

Abstract Introduction: Bortezomib-containing regimens (BCRs) have been the standard frontline approach for the treatment of transplant ineligible multiple myeloma (TIMM) patients in Canada for many years. Based on recent randomized clinical trial results lenalidomide and dexamethasone (Ld) has become another provincially funded option in Canada in the same therapeutic space. We aimed to compare the effect of BCRs and Ld for the treatment of TIMM using the newly-formed Myeloma Canada Research Network Multiple Myeloma Database (MCRN-MM-DB) project. This web-based centralized platform can track and characterize real-world outcomes of patients treated at major Canadian institutions and includes both legacy data dating back to 2007 (from 4 centres) as well as ongoing prospective data collection (from 11 centres) analyzed up to 01/07/18. Patients and Methods: The primary objective was to assess the ORR, PFS and OS for TIMM patients treated with CyBorD/CyBorP, Ld, VMP or VD/VP, each given as reported previously but with dose-adjustments at the discretion of the treating physician to maintain patients on therapy. The two-sided Fisher exact test was used to test for differences between categorical variables. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test; a p value of <0.05 was considered significant. Results: 842 TIMM patients were evaluated. Clinical characteristics are shown in Table 1. Median OS and PFS for the entire cohort were 54.1 and 20.4 months, respectively. ORR and ≥VGPR better rates were 83% and 52% for the entire cohort. A ≥VGPR rate of 53%, 46%, 56% and 51% were observed for patients treated with CyBorD/P, VMP, Ld and VD/VP, respectively (p=0.3). The median PFS was longer for Ld patients (25 months) compared to CyBorD/CyBorP, VMP and Vd/VP (19.3, 20.5 and 13.7 months, respectively), (p=0.03, Fig 1a); there was no significant difference in PFS between the 2 different alkylating-agent containing regimens when combined with bortezomib + steroids (CyBorD/P vs VMP, p =0.9). Median OS was 51, 59.5, 29.4 and 66.5 months for those patients treated with CyBorD/CyBorP, VMP, VD/VP and Ld, respectively (p=0.07, Fig 1b). When the OS and PFS for CyBorD/P (typically given for a fixed duration of 9 cycles) were compared with Ld in a subset analysis, the p-values were 0.08 and 0.008, respectively. Conclusions: 1) OS was not significantly different in patients treated with either a bortezomib-containing triplet that includes an alkylator + steroid or continuous Ld. 2) The BCR triplets and Ld were more efficacious than the bortezomib + steroid doublet (VD/VP) for both OS and PFS although, the small sample size and adverse factors, such as frailty and comorbidities, may have influenced the findings. 3) The results in the real-world setting, i.e., a median PFS in the range of 1.5-2 years and median OS of 4.5-5.5 years, confirm triplet-based BCRs and Ld as current valid standards of care for frontline therapy in TIMM. 5) This study confirms the utility of a large comprehensive national database to benchmark current results for comparison with newer regimens as they are introduced into the Canadian therapeutic landscape. Disclosures Arleigh: Celgene: Honoraria; Janssen: Honoraria. Sebag:Janssen Inc.: Membership on an entity's Board of Directors or advisory committees; Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees; Celgene Canada: Membership on an entity's Board of Directors or advisory committees. Leblanc:Celgene Canada: Membership on an entity's Board of Directors or advisory committees; Janssen Inc.: Membership on an entity's Board of Directors or advisory committees; Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. Louzada:Janssen: Honoraria; Celgene: Honoraria; amgen: Honoraria; pfizer: Honoraria. Venner:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria.

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A Pilot Study of Eptifibatide for Treatment of Acute Pain Episodes in Sickle Cell Disease.

Blood ◽

10.1182/blood.v120.21.2102.2102 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2102-2102

Author(s):

Payal C Desai ◽

Julia Brittain ◽

Susan Jones ◽

Adam McDonald ◽

Douglas R Wilson ◽

...

Keyword(s):

Sickle Cell Disease ◽

Board Of Directors ◽

Sickle Cell ◽

Acute Pain ◽

Research Funding ◽

Point Estimate ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Opioid Use ◽

Advisory Committees

Abstract Abstract 2102 Background: Despite the abundant laboratory evidence of platelet activation and inflammation in sickle cell disease (SCD), the contribution of these changes to the pathogenesis of SCD remains uncertain. Patients with SCD exhibit increased platelet activation in the non-crisis, “steady state,” and further increases with acute pain episodes. In addition, levels of the inflammatory mediator, CD40 ligand (CD40L) are increased in the plasma and significantly reduced in the platelets of SCD patients compared to healthy individuals. CD40L may contribute to the pathogenesis of acute pain episodes. Despite an improved understanding of the pathophysiology of SCD, the treatment of acute pain episodes is supportive. We performed a randomized, placebo-controlled study to evaluate the safety and efficacy of eptifibatide, a synthetic peptide inhibitor of the glycoprotein (GP) IIb/IIIa receptor, in patients with SCD during acute painful episodes. Methods: In this single site placebo-controlled trial, eligible patients admitted for acute painful episodes received eptifibatide (two 180 mg/kg boluses 10 minutes apart, followed by a continuous infusion at 2 mg/kg/min for 6 hours) or placebo at a ratio of 2:1. The Post-Treatment Phase lasted for up to 7 days or until resolution of the crisis, whichever was shorter, but no less than 24 hours after discontinuation of infusion. The Follow-up Phase included safety evaluations obtained 14 to 17 days and 28 to 35 days after discontinuation of infusion. The primary outcomes were major bleeding episodes and the largest observed decrease in platelet count during the study. We also evaluated the effect of eptifibatide on the duration of acute pain episodes, pain intensity, duration of hospitalization, total opioid use and acute chest syndrome. Results: Thirteen patients (SS - 10, Sb0 - 2, SC - 1) were randomized to receive either eptifibatide (N=9; 6 females; median age - 25 years) or placebo (N=4; 3 females; median age - 31 years). One patient in the eptifibatide arm withdrew consent following completion of study drug infusion and 1 patient in the placebo arm was withdrawn early because she did not meet eligibility criteria. In the intent-to-treat analysis, there were no major bleeding episodes in either group (point estimate of difference in eptifibatide vs. placebo proportion: 0.0, 95% CI; −0.60, 0.37).There was one minor bleeding episode in a patient on the eptifibatide arm (point estimate of difference in eptifibatide vs. placebo proportion: 0.11, 95% CI: −0.502, 0.494). There was a trend for the largest decrease in platelet count to be greater in the eptifibatide arm compared to the placebo arm, although the difference was not statistically significant (Hodges-Lehman estimate of location shift for eptifibatide vs. placebo: −82, 95% CI; −281, 54). There was no significant difference in the proportion of patients with thrombocytopenia between the treatment groups (point estimate of difference in eptifibatide vs. placebo proportion: 0.11, 95% CI: −0.587, 0.495). The median time to discharge and the median time to crisis resolution were 3.0 days for both treatment arms. The median total opioid use was 400.2 morphine equivalents (ME) for the eptifibatide group and 1471 ME for the placebo group (Hodges-Lehman estimate of location shift for eptifibatide vs. placebo: −65.8, 95% CI: −2519, 1700). There was one episode of acute chest syndrome in each treatment arm. Conclusions: In this small study of SCD patients hospitalized with acute painful episodes, eptifibatide appeared to be safe, but did not improve the times to crisis resolution or hospital discharge. Eptifibatide was associated with a reduced requirement for opioid analgesics, although the difference was not statistically significant. Clinicaltrials.gov Identifier: NCT00834899. Disclosures: Parise: BD: Consultancy; Biogen-Idec: Consultancy; NIH: Research Funding; AHA: Research Funding; SCDAC-NIH: Membership on an entity's Board of Directors or advisory committees; BRI Milwaukee: Membership on an entity's Board of Directors or advisory committees. Ataga:Pfizer: Consultancy; HemaQuest Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adventrx Pharmaceuticals: Consultancy. Off Label Use: Eptifibatide, a glycoprotein IIb/IIIa inhibitor, was evaluated as treatment for acute pain episodes in patients with sickle cell disease.

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New Perspectives and Challenges Regarding Fertility, Conception and Pregnancy in Hemoglobinopathies. a Multidisciplinary Report of 66 Outcomes

Blood ◽

10.1182/blood-2020-134563 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 22-23

Author(s):

Lorenza Torti ◽

Laura Maffei ◽

Francesco Sorrentino ◽

Paolo De Fabritiis ◽

Donatella Dell'Anna ◽

...

Keyword(s):

Birth Weight ◽

Board Of Directors ◽

Abortion Rate ◽

Diagnostic Methods ◽

Acute Chest Syndrome ◽

Childbearing Age ◽

Advisory Committees ◽

Preterm Babies ◽

Median Birth Weight ◽

Chelating Therapy

Introduction Major thalassemia (TM) and sickle cell disease (SCD), two common genetic hemoglobinopathies, were often fatal 50 years ago. Novel therapeutic and diagnostic methods are increasing lifespan and quality of life. Recent advances in iron chelation for transfusion-dependent hemoglobinopathies have significant improved patient prognosis. Young adult TM and SCD patients often ask about the possibility of conception and pregnancy. The increase in the worldwide movement of carriers and subjects has lead to new cultural, ethical and psychosocial aspects that must be taken into consideration. The present study investigated the fertility rate, maternity/paternity status, need for assisted reproductive techniques (ART), abortion rate, pregnancy/newborn complications in patients with hemoglobinopathies. Methods We followed 130 female (FPs) and male (MPs) patients (F:M=93:37); 75 with TM, 32 with thalassemia intermedia (TI), 13 with SCD and 10 with microdrepanocytosis (MDC). Median age is 55 yo (15-90) for TM+TI and 45 yo (18-79) for SCD+MDC. Pregnancy was reported in 37/52 FP of childbearing age (15-49 yo), and conception in 15 MP with fertility rates of 71% and 70%, respectively. Results We reviewed 66 conceptions from 1999 to 2020. Mother age at pregnancy was between 32-39 yo. Forty-seven pregnancies were spontaneous and 19 medically assisted. There were 3 ovodonations and 2 ICSI; 64% of pregnancies were planned. Pregnancy outcomes of 22 TM, 16 TI, 8 SCD and 3 MDC patients are described. There were 7 miscarriages in the first 12 weeks: 3 in TI, 1 in SCD FP; 1 in TM and 2 in SCD MP. Abortion rate was 9%, comparable to the general population. Intrauterine death at 24w occurred in a SCD FP for placental thrombosis and eclampsia. Sixty live healthy newborns were delivered;4 twin pregnancies occurred (1 TM MP, 3 TM FP). Only 1 malformation was observed, in an infant born after ovodonation in a TM FP who had minor gastroenteric and urinary malformations that were surgically corrected. Obstetric complications were eclampsia, disseminated intravascular coagulation, cardiac failure, and acute chest syndrome in SCD patients. One ovarian hyperstimulation syndrome in the 1st month of pregnancy with ascites and admission to the ER was reported. There were 30 (94%) caesarians (CD) and 3 vaginal deliveries (VG) in FP, with 7 preterm babies (22%). In partners of MPs there were 15 CD (56%), and 11 VG with 5 preterm babies (Table I). Births from MPs occurred between 34-40w with a median birth weight of 3 kg (2.17-4) and 30-41w in FPs with a median birth weight of 2,5 kg (1,1-3,4) . FPs were able to breast fed in 56% of cases for a medium time of 66 days (20-120), while female partners of MPs breastfed for 193 days (20-540). Newborn events includes 14 jaundices; 9 babies were placed in intensive care and required incubator use due to cerebral hemorrhage or infections requiring antibiotic therapy. Discussion Spontaneous pregnancies occur in well chelated and transfused patients but a relevant part of those patients are infertile due to hypogonadism due to transfusional hemosiderosis and may need ART. These patients present a base-line pro-coagulant state which can worsen during pregnancy, needing antithrombotic prophylaxis and require regular consultations, since pregnancies are considered high risk for both mother and baby. As osteopenia-osteoporosis are the common endocrine complications in hemoglobinopathies (67% of FPs), both cesarean delivery and breast feeding are strongly suggested. Even though chelating therapy during lactation does not alter iron excretion, our patients didn't receive chelating therapy when breastfeeding. Multidisciplinary programs including transfusions, cardiac and clinical evaluations should be monthly performed. Our Institution has a team of hematologists and other dedicated specialists that work together during the planning, conception, pregnancy, delivery and immediate post-delivery processes to assure best care to mother and child. Conclusions Survival of hemoglobinopathic patients in developed countries is improving and patients aspire to reproductive aims of their healthy peers. TM and SCD patients often request fertility and pregnancy information, including screening of partners. We provide insights regarding reproductive health experience of hemoglobinopathies in both genders. Detailed results, mothers and child follow up and practical management will be presented. Figure Disclosures Abruzzese: Incyte:Consultancy, Membership on an entity's Board of Directors or advisory committees;Pfizer:Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis:Consultancy, Membership on an entity's Board of Directors or advisory committees;Bms:Honoraria.

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Different Clinical Implications of Kinase Domain BCR-ABL1 Variants Detected in Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia Patients

Blood ◽

10.1182/blood-2019-127069 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5368-5368

Author(s):

Ricardo Sanchez ◽

Rosa Ayala ◽

Gonzalo Carreño Gomez-Tarragona ◽

Espino Maria Jose ◽

Beatriz Cuevas ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Myeloid Leukemia ◽

Research Funding ◽

Poor Prognosis ◽

Lymphoblastic Leukemia ◽

Kinase Domain ◽

Categorical Variables ◽

P Value ◽

Advisory Committees

Background: Kinase domain (KD) mutations is a common resistance mechanism, secondary to the tyrosine-kinase inhibitors (ITKs) treatment in the case of chronic myeloid leukemia (CML) and Philadelphia (Ph)-positive acute lymphoblastic leukemia (ALL) patients. Sanger sequencing is the gold standard technique and already the currently recommended method for BCR-ABL1 KD mutation detection. However, Sanger sequencing has limited sensitivity and cannot firmly identify populations with variant allele frequencies (VAF) < 15-20%. Next-generation sequencing (NGS) allow us the screening of mutations in the whole KD with variants with a VAF greater than 1%. The aim of this study is to evaluate the clinical and prognostic implications of CML and Ph-positive ALL patients who have been studied for mutations in BCR-ABL1 by NGS. Methods: Seventy CML and Ph-pos ALL patients have been studied for BCR-ABL1 mutations between years 2015-2017. The study reason was warning or failure according to European Leukemia Net recommendations in the case of CML patients, and diagnostic or relapse in the case of ALL patients. Clinical characteristics of the patients are depicted on Table 1. Categorical variables are described as frequency, and quantitative variables as medians. Contingency tables were used to analyze associations between categorical variables (χ2). Median test was used to compare medians of continuous variables between groups. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between patients using the log-rank test. Results: We have found 37 patients with mutations (51%), the most frequent being p.T315I, p.L248V and p.L387M. 28 out of 59 were found in CML (47%) vs 9 out of 13 (69%) in ALL. Of the 37 patients with mutations, double mutations have been found 10 times (27%). In the 72 analyses performed, 62 mutations were found in total, 41 of them were variants of uncertain significance (VUS) and 21 were well-known mutation. The median levels of BCR-ABL1 (IS) at the time of analysis were 3.00 (0.01-196.18) %. Regarding CML patients, we have found 12 and 16 cases with pathogenic mutations and VUS, respectively. The mean survival for CML and ALL were 75.2 months (CI 95%, 65.7-84.6) and 24.7 months (13.3-36.2), respectively. There are significant differences between the overall survival curves for patients with CML who have mutations in BCR-ABL1 compared to those who have VUS or do not (p-value = 0.024, n=59), suggesting a second role of the VUS variants in the resistance of the patients to the TKI. These two groups have no significant differences in ALL patients (p-value= 0.32, n=13). Overall survival at 10 years from the date of diagnosis is 74% for CML patients with mutations and 90% for CML patients without mutations. Data dropped significantly for ALL patients, but the number of cases is too low. Conclusions: - Mutations have been identified in 47% of CML patients studied in the case of failure or warning and 69% of the patients of ALL at diagnosis or relapse moments. - The identification of pathogenic variants has poor prognosis in patients with CML (p = 0.024), however no differences were observed in ALL. - The identification of VUS is not associated to poor prognosis and these variants could not confer resistance to ITK. Disclosures Sevilla: Rocket Pharmaceuticals, Inc.: Honoraria, Patents & Royalties: Inventor on patents on lentiviral vectors filled by CIEMAT, CIBERER and F.J.D and may be entitled to receive financial benefits from the licensing of such patents; NOVARTIS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Rocket: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Miltenyi Biotech: Honoraria. Steegmann:Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. García Gutiérrez:Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Incyte: Honoraria, Research Funding.

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