Cost-Effectiveness of Blood Transfusions Versus Observation for Silent Cerebral Infarcts from the Silent Cerebral Infarct Trial

Abstract BACKGROUND AND OBJECTIVE: In the Silent Cerebral Infarct Trial (SIT), regular blood transfusion therapy significantly reduced the incidence of recurrent cerebral infarctions in children with sickle cell anemia (SCA). As a follow-up analysis of the SIT Trial, we compared healthcare utilization, as measured by adverse events, hospitalizations and costs in regularly transfused children (transfusion group) to those who were not transfused (observation group). <>METHODS: In this multi-center trial, we randomly allocated 196 children aged 5-15 years with SCA and prior history of silent cerebral infarcts (SCI) to receive monthly blood transfusion or observation for at least 36 months or until a study endpoint was reached. The number of and reasons for hospitalizations were recorded at each site. The transfusion group was determined by a protocol approach, with all patients receiving regular transfusions over a period of at least 6 months included, irrespective of the original group assignment in the SIT study. Estimated costs per day of hospitalization were determined using data obtained from the 14 SIT institutions which contributed administrative data to the Pediatric Health Information System (PHIS) database maintained by the Children's Hospital Association. Inpatient costs were based on length of hospital stay, modified by the occurrence of categories of adverse events in the following non-overlapping hierarchy: acute chest syndrome, vaso-occlusive pain crisis, fever/infection, exchange transfusion, surgery and asthma. Outpatient expenses not related to transfusion or iron chelation were considered equivalent for transfused patients and controls for the purposes of this study and were not included in the costing model. Chelation and blood transfusion costs were based on a child that weighed 30 kg and received 20 mg/kg/day of deferoxamine or deferasirox. Follow-up occurred from time of random allocation to primary endpoint (overt stroke or new or progression of SCI) or exit MRI, whichever came first. The SIT Trial is registered at www.clinicaltrials.gov (NCT00072761). <> <>RESULTS: A total of 90 and 106 patients comprised the final transfusion and observation groups, respectively. Fifteen of the patients originally randomly allocated to the transfusion group crossed over to the observation group by either never receiving blood transfusion (N=9) or receiving less than 6 months of regular blood transfusion (N=6) and were counted as not being effectively transfused (i.e., part of the observation group). The mean follow up for individuals who did or did not receive blood transfusion therapy was 3.04 and 3.01 years, respectively. The average age of all participants at randomization was 10.0 years, with 43.4% males. There were 144 hospitalizations in the transfusion group and 269 in the observation group; average length of hospital stay was 2.5±1.8 days vs. 3.4±2.2 days for transfused and observation groups, respectively (p<0.001). An average of 1.6 and 2.5 hospitalizations occurred per patient with a total of 358 and 912 patient days for patients in the transfusion and observation groups, respectively. The most common reason for hospitalization was an acute pain episode (49.6%), followed by acute chest syndrome (9.4%). For every 100 children with history of SCI treated with regular blood transfusions for one year, there were 71 fewer hospital days for all SCA-related conditions per SCI prevented (157 fewer days/2.19 fewer SCIs) when compared to 100 children with SCA and history of SCIs who are not treated with transfusion therapy. Hospitalization costs were reduced 54% per year ($4,302 vs. $9,407) for children receiving blood transfusion therapy compared to those observed. Total yearly costs not related to hospitalization for patients in the transfusion group ranged from $18,149 to $67,361/year, depending on the estimated costs for the type of chelation used and type of red blood cell transfusion (manual partial exchange or apheresis). (Table) CONCLUSIONS: Children with SCA and silent cerebral infarcts receiving regular blood transfusions have a 54% relative reduction in hospitalization cost when compared to children with SCA; however their outpatient costs of monthly prophylactic blood transfusions are high and heavily dependent upon the type of blood transfusion therapy and choice of chelation therapy. Table Table. Disclosures McCavit: Novartis: Speakers Bureau; Pfizer: Consultancy, Research Funding. King:HRSA: Research Funding; NIH - NHLBI: Research Funding; NIH - BMTCTN: Research Funding. Strouse:NHLBI: Research Funding; HRSA: Consultancy; Maryland Dept of Health and Mental Hygiene: Research Funding; HRSA: Research Funding. Casella:Johns Hopkins: Patents & Royalties; Mast Therapeutics: Research Funding; ImmunArray: Patents & Royalties.

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Association of Hospitalization Due to Vaso-Occlusive Crisis with Subsequent Sickle Cell Disease-Related Organ Damage Hospitalization: Retrospective Analysis of 3-Year Observational Study Data

Blood ◽

10.1182/blood-2021-144723 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2037-2037

Author(s):

Matthew M. Heeney ◽

Thirupathi Pattipaka ◽

Jilles M. Fermont

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Gallbladder Disease ◽

Organ Damage ◽

Study Data ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Advisory Committees ◽

History Of

Abstract Background: Hospitalization due to vaso-occlusive crisis (H-VOC) is common in individuals with sickle cell disease (SCD), with an increasing occurrence of SCD-related complications, including organ damage, as the disease progresses. Evidence regarding the relationship between H-VOC and SCD-related organ damage, however, is lacking. Aim: To assess whether H-VOC is associated with hospitalization due to SCD-related organ damage, through retrospective analysis of data collected prospectively during a 3-year, multicenter, observational US study (NCT01220115) that aimed to better understand disease burden and management of SCD in individuals aged ≥2 years. Methods: Of the 498 individuals with SCD who were recruited into the US study, data were analyzed from 202 (100 men and 102 women) who were aged ≥16 years and had available hospital admission data. Organ damage was defined based on hospital discharge diagnosis. 1 Variables tested at baseline, in addition to H-VOC, included demographics, blood measures, and treatment history. Age and sex were included by default in all models based on literature suggesting they are relevant factors influencing organ damage. Hazard ratios (HRs) for the time from H-VOC to the first subsequent hospitalization due to SCD-related organ damage were estimated using multivariable Cox regression. Worsening of pre-existing organ damage was not considered as an event due to potential confounding (ie worsening of organ damage related to the pre-existing condition rather than as a consequence of the VOC). Results: During median 3-year follow-up, 55 (27%) individuals experienced at least one hospitalization due to SCD-related organ damage; 2 19 (9%) had multiple visits. Within the 12 months preceding baseline, 22 (11%) individuals had a history of organ damage, there was a median of two H-VOC in the 90 (45%) individuals with history of H-VOC, and 43 (21%) individuals had received chronic transfusion (≥6). History of H-VOC (HR 2.54, 95% confidence interval [CI] 1.46 to 4.43 in past 12 months), genotype (HR 2.69, 95% CI 1.34 to 5.41 for HbSS), and sex (HR 1.90, 95% CI 1.08 to 3.34 for women) were all significantly associated with subsequent hospitalization for SCD-related organ damage. Discussion and conclusion: This analysis demonstrates that history of H-VOC within the preceding 12 months is significantly associated with a higher rate of subsequent hospitalization due to SCD-related organ damage, independent of age, sex, and genotype, and may therefore help identify individuals at high risk of developing organ damage. Despite 21% of individuals receiving chronic transfusions at baseline, this factor did not remain significantly associated with the outcome when also considering genotype and H-VOC. Age and sex were unexpectedly insignificantly associated with the outcome; this is likely due to the relatively short follow-up time. Extending the historical timeframe of organ damage to 5 years did not change our findings, except that age also became significantly associated with subsequent hospitalization for organ damage. Acute chest syndrome and pneumonia were the most common types of historical (baseline) organ damage, whilst gallbladder disease was the most common organ damage observed during the follow-up period that was not observed at baseline. Our data have limited statistical power and generalizability; additional studies are required to confirm these findings. Nevertheless, our findings support the existing evidence of the impact that VOCs may have on individuals with SCD, and highlights the importance of preventing and reducing H-VOC. 1Acute chest syndrome or pneumonia; avascular bone necrosis of hip(s), shoulder(s) or spine; cardiac failure; central nervous system disease (ie abnormal transcranial Doppler, silent infarct, stroke and transient ischemic attack); gallbladder disease; leg ulcer; liver disease (ie hepatic fibrosis/ cirrhosis, hepatic sequestration/sickle-hepatopathy/intrahepatic sickling, pulmonary fibrosis, pulmonary hypertension); priapism; renal disease (ie acute renal failure, chronic renal failure-supportive, dialysis, microalbuminuria/ proteinuria, transplant); retinopathy; and splenic sequestration. 2The top 3 reasons for hospitalization due to SCD-related organ damage were acute chest syndrome or pneumonia (n=29; 53%), renal disease (n=7; 13%) and gallbladder disease (n=6; 11%). Figure 1 Figure 1. Disclosures Heeney: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; FORMA: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Vertex / Crispr Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; bluebird bio: Consultancy; Keros: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Cyclerion: Consultancy, Membership on an entity's Board of Directors or advisory committees. Pattipaka: Novartis: Current Employment, Current holder of individual stocks in a privately-held company. Fermont: Novartis Pharma AG, Basel, Switzerland: Current Employment, Current equity holder in publicly-traded company.

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Efficacy and Safety of a FLAG-Sequential Regimen Followed By Hematopoietic Stem Cell Transplantation for Myelodysplasia or Acute Leukemia in Fanconi Anemia: A Franco-Brazilian Report

Blood ◽

10.1182/blood-2019-122007 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2498-2498

Author(s):

Pierre-Edouard Debureaux ◽

Flore Sicre de Fontbrune ◽

Carmem M. S. Bonfim ◽

Jean-Hugues Dalle ◽

Nimrod Buchbinder ◽

...

Keyword(s):

Cumulative Incidence ◽

Research Funding ◽

Bone Marrow Failure ◽

Clonal Evolution ◽

Infectious Complications ◽

Hematopoietic Stem ◽

Free Survival ◽

History Of ◽

Syncytial Virus

Background: Fanconi anemia (FA) is the most frequent genetic cause of bone marrow failure (BMF) due to a DNA repair mechanism defect. The natural history of FA is marked by progressive BMF during early childhood. Throughout life, the hematopoietic situation may change by clonal evolution toward myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for bone marrow failure in FA patients. The role of HSCT for FA patients with AML or advanced MDS is less defined. Currently, HSCT first line result offers 50% Overall Survival (OS) for patients with cytogenetic abnormalities only and 30% OS for patients with advanced MDS or AML in FA (Ayas et al., JCO 2013; Mitchell et al., BJH 2014). We previously reported a FLAG-sequential approach in 6 patients with FA (5 AML and 1 advanced MDS), all alive at a median follow-up of 28 months (Talbot et al., Hematologica 2014). We update here those patients and report 12 more patients treated by FLAG-sequential since then. Materials & Methods: This retrospective study (2006-2019) was conducted in 7 centers in France and Brazil on behalf of the French Reference Center for Aplastic Anemia to evaluate FLAG-sequential in FA patients with morphological clonal evolution (no patients with cytogenetic abnormalities only). The study was conducted in accordance with the Declaration of Helsinki. Anonymous data collection was declared to the appropriate authorities. The FLAG-sequential treatment consisted of FLAG, Fludarabine 30 mg/m²/d for five days and Cytarabine 1 g/m²x2/d with G-CSF for five days, which was followed three weeks later by Cyclophosphamide 10 mg/kg/d for four days, Fludarabine 30 mg/m²/d for four days and TBI 2 Gy (Fig 1A). In a haploidentical setting, Cyclophosphamide at 30 mg/kg/d was performed only in post-transplantation, at Days +4 and +5 (Fig 1B). Results: Eighteen patients were included with 14 AML, 1 acute lymphoblastic leukemia (ALL), and 3 RAEB-2 (Table 1). The median age at the time of HSCT was 22 years (4-37 years). Fifteen patients (83%) were older than 10 years at the time of HSCT. The median follow-up was 31 months (3- 153 months). Eight patients (44%) had complex karyotype. None of the included patients had a history of solid malignancies before HSCT. All patients engrafted. The cumulative incidence of neutrophil engraftment at Day 60 was 94% (95% CI 63-100%) with a median of 18 days (12-343 days). The cumulative incidence of platelet engraftment at Day 60 was 83% (95% CI 50%-96%) with a median of 25 days (17-245 days). The donor chimerism was complete at Day +100 for 15 patients. The three patients without full donor chimerism at Day +100 either had a relapse (n=1) and 2 early deaths before Day+100 from steroid-refractory aGVHD (n=1) or septic shock (n=1). None of the patients received a second HSCT. Non-relapse mortality (NRM) at 3 years was 32% (95% CI 6-58%) (Fig 2). Cumulative incidence of grades II to IV aGVHD was 56% (35% grades III to IV). Cumulative incidence of extensive cGVHD was 16%. Infectious complications during HSCT include the following: CMV (n=8), EBV (n=2), adenovirus (n=4), BK virus (n=7), respiratory syncytial virus (n=1), candidaemias (n=2) and invasive aspergillosis (n=3). Progression free survival (PFS) and OS at 3 years were 53% (95%CI 32-89%) and 53% (95%CI 32-89%), respectively (Fig 2). Cumulative incidence of relapse at 3 years was 13% (95%CI 0-31%) (Fig 2). Seven patients died during the study. Causes of death were relapse (n=2), aGVHD (n=2), cGVHD (n=1), septic shock (n=1), and respiratory syncytial virus associated with invasive aspergillosis (n=1). GVHD-relapse free survival (GRFS) at 3 years was 48% (95%CI 29-78%). One patient had anal epidermoid carcinoma at 4 years after HSCT, which required multiple surgical ablations. Conclusion: With almost 3 years follow-up, which is long enough for our results to be considered robust, we report an OS and PFS of 53%, which compares favorably to historical controls since all of our 18 patients were treated with florid disease at time of HSCT (and not with cytogenetic abnormality only, known to be associated with a better prognosis). Toxicity is still a concern in this particular population of FA patients with notably a high rate of infectious complications. Future well designed prospective clinical trials will refine this sequential strategy, which appears promising in this particular difficult clinical situation. Disclosures Socie: Alexion: Consultancy. Peffault de Latour:Alexion: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Research Funding.

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Predictors of Mortality in Children and Adolescents with Sickle Cell Disease: The PUSH Study

Blood ◽

10.1182/blood.v118.21.515.515 ◽

2011 ◽

Vol 118 (21) ◽

pp. 515-515 ◽

Cited By ~ 1

Author(s):

Mehdi Nouraie ◽

Sohail R. Rana ◽

Oswaldo L Castro ◽

Lori Luchtman-Jones ◽

Craig Sable ◽

...

Keyword(s):

Sickle Cell Disease ◽

Children And Adolescents ◽

Sickle Cell ◽

Severe Pain ◽

Blood Transfusions ◽

Cell Disease ◽

Risk Of Death ◽

The Past ◽

History Of

Abstract Abstract 515 Background: Recent studies indicate that the disease-specific mortality In sickle cell anemia is about 6% in children up to 18 years and 15% in the 18–30 year age group, yielding a cumulative mortality of 21% by age 30 years. It is important to identify children at high risk so that early interventions can be developed to reduce this high mortality. Methods: We prospectively enrolled 505 children and adolescents with sickle cell disease in 2005–2010, 380 with hemoglobin SS and 130 with other genotypes. The median age at enrollment was 12 years with a range of 3 to 20 years. Baseline clinical features, echocardiography, six-minute walk test and pulmonary function testing were performed at steady-state. Follow-up for mortality has been performed in 470 of the participants at a median of 37 months after enrollment, range of 1 to 59 months. Results: Six of 470 patients (1.3%) died during the follow-up period, five with hemoglobin SS and one with hemoglobin SC. The median age at the time of death in these six participants was 20 years, range of 15 to 23 years. Death occurred during the follow-up period in 2.7% of participants over 12 years of age at enrollment and 3.7% of those over 15 years of age. The causes of death were stroke in 4, multiorgan failure in 1 and unknown in 1. Death occurred in 5.9% of 51 participants with a history of stroke versus 0.7% of 416 without stroke history; in 3.5% of 113 participants with a history of asthma versus 0.6% of 354 without asthma history; in 4.9% of 103 participants with 10 or more blood transfusions lifetime versus 0.3% of 359 with less than 10 blood transfusions; in 3.3% of 90 participants with two or more severe pain episodes in the past year versus 0.8% of 380 participants with less than two severe pain episodes in the past year. In age-adjusted analyses, the hazards ratio (95% CI) of death was 6.1 (1.2-30.5) for history of stroke (P=0.029), 10.2 (1.2-89.5) for history of frequent blood transfusions (P=0.036), 5.8 (1.1-31.8) for history of asthma (P=0.044) and 1.07 (1.00-1.14) for frequent severe pain episodes (P=0.047). Clinical findings associated with these risk factors included higher concentrations of markers of hemolysis for history of stroke and history of frequent blood transfusions, decreased FEV1/FVC and increased total lung capacity for history of asthma, and lower concentrations of markers of hemolysis and high ECHO-determined tricuspid regurgitation velocity for history of frequent severe pain episodes. Conclusions: Over a median of three years of observation of this cohort, no deaths occurred among 248 sickle cell disease children 12 years of age or younger at enrollment but there were 6 deaths among 222 participants 13–20 years of age at enrollment. In bi-variate age-adjusted analyses, histories of stroke, asthma, frequent blood transfusions and frequent pain episodes were associated with an increased risk of death. Strikingly, four of the five deaths in which the cause was known were due to stroke. The present data on mortality in the PUSH study suggest that prevention of stroke is critical in improving the survival in adolescents and young adults with sickle cell disease. Disclosures: No relevant conflicts of interest to declare.

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Atrial Fibrillation in Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽

10.1182/blood.v126.23.2950.2950 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2950-2950 ◽

Cited By ~ 4

Author(s):

Tait D. Shanafelt ◽

Kari G. Chaffee ◽

Timothy G. Call ◽

Sameer A. Parikh ◽

Susan M. Schwager ◽

...

Keyword(s):

Atrial Fibrillation ◽

Heart Disease ◽

Valvular Heart Disease ◽

Research Funding ◽

Newly Diagnosed ◽

Advisory Committees ◽

Increased Risk ◽

History Of ◽

Male Sex

Abstract BACKGROUND: Consistent with the advanced age at diagnosis (median age ~70 years), most patients with CLL have co-existent health problems. These co-morbidities influence the ability of many CLL patients to tolerate aggressive chemotherapy-based treatment and can also contribute to treatment-related side effects. The recent development of novel signaling inhibitors, particularly the Bruton's tyrosine kinase inhibitor ibrutinib, has been a major treatment advance for patients with CLL. While these agents generally have favorable toxicity profiles relative to standard chemotherapy-based treatments, they are chronic therapies which patients typically stay on for an extended period. Preliminary data suggests ibrutinib may be associated with an increased risk of atrial fibrillation (Afib). In one randomized trial comparing ibrutinib to ofatumumab in patient with relapsed CLL, incident grade 3+ Afib occurred in 3% of ibrutinib treated patients compared to 0% of ofatumumab treated patients (NEJM 371:213). Despite these observations, the baseline frequency of Afib in patients with CLL is not well described - particularly incident atrial fibrillation acquired during the course of the disease. METHODS: We used the Mayo Clinic CLL database to evaluate the prevalence of Afib at the time of CLL diagnosis as well as the incidence of Afib during follow-up. All patients with a new diagnosis of CLL after January 1995 who were seen at Mayo within 12 months of diagnosis were included in the analysis. Afib was identified by chart review and by billing search using ICD9 codes. Data on co-morbid conditions associated with risk of Afib was also abstracted (e.g. hypertension, coronary artery disease [CAD], valvular heart disease, cardiomyopathy, diabetes mellitus, pulmonary disease). RESULTS: A total of 2444 patients with newly diagnosed and previously untreated CLL were seen at Mayo Clinic within 12 months of diagnosis between 1/1995 and 4/2015.Median age at diagnosis was 65 years and 1626 (66.5%) patients were men. A history of Afib was present at the time of CLL diagnosis in 148 (6.1%) patients. Four additional patients had Afib documented in the record but the precise date of onset (e.g. prior to or after CLL diagnosis date) could not be determined. Age, male sex and history of CAD, valvular heart disease, cardiomyopathy, hypertension, and diabetes were associated with a greater likelihood of having a history of Afib at the time of CLL diagnosis (all p<0.01). Among the 2292 patients without a history of Afib at CLL diagnosis, 139 (6.1%) had incident Afib during the course of follow-up for their CLL. The incidence of Afib among patients without a history of Afib at diagnosis was approximately 1%/year (Figure 1A). Considering both Afib present at the time of CLL diagnosis or acquired during the course of the disease, 291 (11.9%) of the 2444 patients in this cohort experienced Afib (median follow-up: 59 months). Among patients without Afib at the time of CLL diagnosis, the following characteristics at the time of CLL diagnosis were associated with an increased risk of incident Afib on multivariate analysis: older age (age 65-74 HR=2.4, p<0.001; age ≥75 HR=3.6, p<0.001), male sex (HR=1.8, p=0.004); valvular heart disease (HR=2.4, p=0.007), and hypertension (HR=1.5; p=0.02). A predictive model for acquired Afib was subsequently constructed based on the independent factors in the Cox regression model. An individual weighted risk score was assigned to each independent factor based on the regression coefficients of the HRs. The Afib risk score (range 0-7) was defined as the sum of the scores of these independent factors. The risk of incident Afib among patients with risk scores of 0-1, 2-3, 4, and 5+ is shown in Figure 1B. Rates for these 4 groups were significantly different (p<0.001), with the 10-year Afib rates (95% C.I.) for those with a score of 0-1, 2-3, 4, and 5+: 4% (2-6%), 9% (6-13%), 17% (11-23%), and 33% (20-43%), respectively. CONCLUSIONS: A history of Afib is present in approximately 1 out of every 16 patients with newly diagnosed CLL. Among patients without Afib at diagnosis, the incidence rate of Afib is ~1%/year. The risk of incident Afib in newly diagnosed CLL patients can be predicted based on age, sex, and co-morbid health conditions present at diagnosis. These data provide context to help interpret data on the frequency of Afib in CLL patients treated with ibrutinib and other novel agents. Disclosures Shanafelt: Janssen: Research Funding; Polyphenon E Int'l: Research Funding; Glaxo-Smith_Kline: Research Funding; Cephalon: Research Funding; Genentech: Research Funding; Hospira: Research Funding; Celgene: Research Funding; Pharmactckucs: Research Funding. Ding:Merek: Research Funding. Kay:Tolero Pharm: Research Funding; Hospira: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Therapy Preference and Outcomes of Hydroxyurea for Pediatric Patients with Silent Cerebral Infarcts

Blood ◽

10.1182/blood.v128.22.3531.3531 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3531-3531

Author(s):

Tullia Rushton ◽

Inmaculada Aban ◽

Daniel Young ◽

Thomas H. Howard ◽

Lee Hilliard ◽

...

Keyword(s):

Randomized Trial ◽

Sample Size ◽

Research Funding ◽

Retrospective Chart Review ◽

Initial Therapy ◽

Pediatric Radiologist ◽

Transfusion Therapy ◽

Exact Test ◽

Number Of Patients ◽

History Of

Abstract Introduction: The Silent Infarct Transfusion (SIT) Trial demonstrated that transfusion therapy over three years, as compared to no sickle cell disease (SCD) modifying therapy, reduces the risk of new CNS events, defined as an overt stroke or new or enlarged silent cerebral infarct (SCI), in patients with SCI on screening MRI. Despite the significant reduction in CNS events with transfusion therapy, patients/caregivers may choose to decline chronic transfusion therapy for secondary CNS events. Hydroxyurea is known to decrease complications of SCD, and while its impact on new CNS events in patients with a SCI has not been tested in a randomized trial, it was offered as an alternative for patients who declined transfusion therapy. We evaluated therapy preference for prevention of new CNS events among patients with SCI on screening MRI and three year outcomes of patients with SCI that elected treatment with hydroxyurea at our institution. Methods: We performed a 15-year IRB approved retrospective chart review for all patients with the diagnosis of SCI at Children's of Alabama based on their original MRI report. Ninety-two patients were identified and subsequently confirmed by an additional pediatric radiologist to have suffered a SCI and had no history of a prior overt stroke while 39 patients were excluded because of their history of overt stroke prior to the detection of a SCI. We recorded the patient/caregiver initial preference for therapy and evaluated differences in therapy selection prior to, during, and post SIT Trial. We recommend annual or biennial follow-up MRI exams to evaluate for SCI progression and recorded and reviewed all subsequent MRIs and SCD therapies for overt stroke or new or enlarged SCI. To compare outcomes of hydroxyurea for secondary CNS events to the SIT Trial, we evaluated the 27 patients with SCI that were treated with hydroxyurea (HU) for their SCI and had a subsequent MRI/MRA at least three years after their initial diagnosis of SCI. Descriptive statistics and Fisher's exact test were performed using JMP10. Sample size was calculated for a superiority trial design using a power of 85% and alpha of 5% with PASS version 14. Results: We evaluated patient/caregiver therapy preference for secondary SCI prevention among 54 patients that were not receiving a SCD modifying therapy at the time of their index SCI. We identified a significantly higher number of patients/caregivers who, after discussion with their primary SCD provider about therapeutic options, elected to initiate transfusion or enroll in the SIT Trial prior to and during SIT Trial enrollment but a higher percentage of patients/families that elected to initiate hydroxyurea after enrollment (p=0.04). Three of 36 patients (8%) elected hydroxyurea prior to and during SIT Trial enrollment as compared to 6 of 18 patients (33%) post enrollment. Among 27 participants on HU at the time of their incident SCI finding on MRI, 25 (93%) participants elected to remain on HU while only two (11%) participants elected to change to chronic transfusion therapy. The two patients that switched to transfusion also had MRA abnormalities identified at the time of their incident SCI finding. To evaluate outcomes of HU for secondary SCI prevention, 27 participants were prescribed HU for at least three years and underwent serial MRI evaluations. Three of these 27 participants developed a new SCI. Four participants had an abnormal MRA at the time of their index MRI and five patients developed an abnormal MRA on subsequent studies. The three participants that had an additional SCI had normal MRA examinations. In comparison to the SIT Trial, which identified 2.0 and 4.8 new CNS events per 100 patient years at risk for transfusion and no therapy respectively, we identified 3.7 new CNS events per 100 patient years among patients prescribed hydroxyurea. Combining our results with that of SIT Trial, a sample size of 1100 participants would be required to conduct a trial to show the superiority of transfusion over HU for secondary SCI. Conclusion: While the SIT Trial showed chronic transfusion to be superior to no therapy in preventing new CNS events in patients with SCI, patients and caregivers at our institution prefer hydroxyurea to transfusion for initial therapy to prevent secondary CNS events. A randomized trial to show superiority of transfusion over hydroxyurea for secondary stroke prevention would require a sample size too large to be practical. Disclosures Lebensburger: NHLBI: Research Funding; American Society of Hematology, Scholar Award: Research Funding.

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Skin Cancers Among Chronic Lymphocytic Leukemia (CLL) Patients - the Effect of UV Radiation and CLL Clinical Characteristics

Blood ◽

10.1182/blood.v128.22.4772.4772 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4772-4772 ◽

Cited By ~ 4

Author(s):

Geffen Kleinstern ◽

Abdul Rishi ◽

Sara J Achenbach ◽

Kari Rabe Chaffee ◽

Neil E. Kay ◽

...

Keyword(s):

Skin Cancer ◽

Uv Radiation ◽

Mayo Clinic ◽

Research Funding ◽

Sun Exposure ◽

Prior History ◽

Skin Cancers ◽

History Of ◽

Very High

Abstract Background: It is well established that the incidence of skin cancers in patients with CLL are significantly elevated compared to age- and sex- matched controls. However, little is known about the characteristics of CLL patients who develop skin cancer. Herein, we evaluate the associations of CLL clinical and prognostic characteristics, along with UV radiation exposure, with risk of first skin cancer following CLL diagnosis. Methods: Newly diagnosed CLL patients from Minnesota, Iowa, and Wisconsin were enrolled in the Mayo Clinic case-control study from 2002-2015 and systematically followed in the Iowa/Mayo Lymphoma SPORE. Clinical and prognostic CLL data were obtained from the Mayo Clinic CLL database, and skin cancer clinical data were abstracted from medical records using a standard protocol. The CLL international prognostic index (CLL-IPI) was computed using a weighted average of five independent CLL prognostic factors (IGHV mutational status, serum b2-microglobulin, Rai stage, age, and FISH 17p deletion/TP53 status). Self-reported history of midday sun exposure at various ages (birth to age 12; 13 to 21 years; 22 to 40 years, and 41+ years) was obtained from a risk factor questionnaire. For each age, we asked the extent of mid-day sun as: practically no exposure (under 3 hours per week), little exposure (4-7 hours per week), moderate exposure (8 to 14 hours per week) and extensive exposure (15+ hours per week). Midday sun exposure was modeled as an ordinal covariate. To evaluate associations with risk of skin cancer following CLL diagnosis, we calculated time from date of CLL diagnosis to date of first skin cancer, death, or last known follow-up. We used Cox regression analysis to estimate hazard ratios (HRs) and 95% CIs. CLL treatment was considered a time-dependent covariate. Results: Among 846 CLL patients enrolled, the median age at diagnosis was 63 years (range 28-91), 68% were male, 7% had Rai stage III-IV at diagnosis. Based on the CLL-IPI, 42% were categorized as low risk, 33% as intermediate risk, and 25% as high or very-high risk. 109 CLL cases (13%) had one or more reported skin cancers at or prior to CLL diagnosis. Melanoma was observed in 19 (2%) cases and non-melanoma was in 90 (11%) cases. At a median follow-up of 7 years from CLL diagnosis, 165 patients (20%) had one or more skin cancers after CLL diagnosis. Among these patients, 49 had skin cancer before CLL diagnosis. The most frequent skin cancer was squamous cell carcinoma (59%), followed by basal cell (31%), melanoma (5%), and Merkel cell (1%). 552 (65%) of the 846 patients returned a questionnaire. Significant associations of clinical and prognostic characteristics with risk of first skin cancer were observed for age (HR=1.35 per 10 year increase, 95% CI=1.17-1.56, P<0.001), male sex (HR=1.38, 95% CI 0.98-1.96, p=0.07), prior history of skin cancer (HR=4.19, 95% CI=2.98-5.88, P<0.001), and CLL-IPI (HR=1.26, 95% CI= 1.03-1.54, P=0.026, after adjusting for age, sex, and prior skin cancer). Of note, the risk of first skin cancer in those CLL patients categorized as very high via CLL-IPI had 2.28 fold risk (95% CI 1.02-5.11). Midday sun exposures for each of the ages considered showed no evidence of association with risk of first skin cancer (all P>0.05). 50 CLL patients were treated prior to first skin cancer following CLL diagnosis; we observed no evidence of association between treatment and risk of first skin cancer (HR=1.44, 95% CI= 0.93-1.92, P=0.12). Conclusion: CLL patients who are at an increased risk of skin cancer following CLL diagnosis are those who either have had a prior history of skin cancer or a more aggressive CLL disease at diagnosis, according to CLL IPI. Routine skin cancer screening is currently recommended for CLL patients. Our data suggest that more frequent screening would be particularly important among patients with aggressive CLL and who have a prior history of skin cancer. Unexpectedly, we found no evidence of association of skin cancer risk with UV radiation following CLL diagnosis or with CLL treatment. Further investigation is needed to determine whether other factors increase the risk of skin cancer following CLL diagnosis. Disclosures Shanafelt: Genentech: Research Funding; GlaxoSmithkKine: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Cephalon: Research Funding; Pharmacyclics: Research Funding; Hospira: Research Funding.

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Five years of experience with hydroxyurea in children and young adults with sickle cell disease

Blood ◽

10.1182/blood.v97.11.3628 ◽

2001 ◽

Vol 97 (11) ◽

pp. 3628-3632 ◽

Cited By ~ 132

Author(s):

Alina Ferster ◽

Parvine Tahriri ◽

Christiane Vermylen ◽

Geneviève Sturbois ◽

Francis Corazza ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Laboratory Data ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Significant Difference ◽

History Of ◽

Ischemic Attack

The short-term beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) has been proven by randomized studies in children and adults. The Belgian registry of HU-treated SCD patients was created to evaluate its long-term efficacy and toxicity. The median follow-up of the 93 patients registered is 3.5 years; clinical and laboratory data have been obtained for 82 patients at 1 year, 61 at 2 years, 44 at 3 years, 33 at 4 years, and 22 after 5 years. On HU, the number of hospitalizations and days hospitalized dropped significantly. Analysis of the 22 patients with a minimum of 5 years of follow-up confirm a significant difference in the number of hospitalizations (P = .0002) and days in the hospital (P < .01), throughout the treatment when compared to prior to HU therapy. The probabilities of not experiencing any event or any vaso-occlusive crisis requiring hospitalization during the 5 years of treatment were, respectively, 47% and 55%. On HU, the rate per 100 patient-years of severe events was estimated to be 3.5% for acute chest syndrome, 1.2% for aplastic crisis, 0.4% for splenic sequestration; it was 0% for the 9 patients with a history of stroke or transient ischemic attack followed for an average of 4 years. No important adverse effect occurred. Long-term chronic treatment with HU for patients with SCD appears feasible, effective, and devoid of any major toxicity; in patients with a history of stroke, HU may be a valid alternative to chronic transfusion support.

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Safety and Efficacy of Venetoclax-Based Treatment in Elderly CLL Patients: A Retrospective Study from the Filo Group

Blood ◽

10.1182/blood-2021-149640 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3747-3747

Author(s):

Charlotte Doublet ◽

Marie-Sarah Dilhuydy ◽

Emmanuelle Ferrant ◽

Pierre Feugier ◽

Alexandra Fayault ◽

...

Keyword(s):

Retrospective Study ◽

Board Of Directors ◽

Research Funding ◽

Progression Free Survival ◽

Oncology Nurses ◽

Advisory Committees ◽

Free Survival ◽

Daily Dose ◽

History Of

Abstract Median age at diagnosis of chronic lymphocytic leukemia is 72 years. However, only few patients over 80 years of age are included in clinical trials, even in those devoted to unfit patients. In order to evaluate both efficiency and safety of venetoclax in this category of patients, we conducted a multicentric retrospective study and collected data from 77 CLL patients from 19 FILO centers who started venetoclax after 80 years of age. Median age at venetoclax initiation was 86 years old (81-97). 63% of patients had a history of heart disease, 62% had renal failure (moderate 59% and severe 3%) and 29% had a history of severe infections. Despite their comorbidities and a CIRS greater than 6 in 70% of cases, their autonomy was preserved with a median performans status of 1 (0-4). In this comorbid geriatric population, pretherapeutic geriatric assessment was only performed in a single patient. The median number of prior therapies was 2 (0-6) with an exposure to a BCR inhibitor in 56% of cases. 11q and 17p deletion were found in 39% and 30% of cases respectively, 39% of patients had a complex karyotype and 30% harbored a TP53 mutation. However, in this real life population, these prognostic factors were only performed in half of patients. IGHV mutational status was only available in 11 patients, and 83% of them had unmutated IGHV. At the time of venetoclax initiation, the tumor lysis syndrome (TLS) risk was moderate in 57% of cases and high in 8% of cases. Venetoclax was administered as a single agent (42%) or in association with rituximab (58%). In total, half of the patients were hospitalized at each dose ramp-up, and only 3 patients were treated on outpatient basis. 82% of the cohort was able to reach the daily dose of 400mg. Half of the patients were included in a phone call monitoring program with oncology nurses to pre-emptively manage side effects and foster therapy adherence. The safety study reported 14% of TLS, with 2 discontinuations of treatment within the first month: one of which led to dialysis and the other to death. As in the previously published studies, 25% of patients had infectious complications, and grade 3 haematological and digestive toxicities were reported in 42% and 22% of cases, respectively. The reduction of the daily dose of venetoclax was necessary for 33%. Permanent discontinuation of venetoclax occurred in 40% of subjects, including 29% of early withdrawal (within the first 3 months). Main reasons for discontinuation were intolerance (21%), CLL progression (21%), death (21%) and scheduled treatment discontinuation (10%). The overall response rate was 86%, consisting of 49% of complete response (unconfirmed by bone marrow biopsy) and 37% of partial response. With a median follow-up of 21months, estimated progression free survival and overall survival were 29 and 38 months respectively. Prior exposure to a BCR inhibitor had no impact on progression free survival. To conclude, venetoclax has a manageable safety profile in elderly patients with comorbidities and can induce prolonged responses. Finally, if additional follow-up by oncology nurses seems to be more and more implemented, the pre-therapeutic onco-geriatric evaluation remains underexploited in this population. Disclosures Ferrant: AstraZeneca: Honoraria; AbbVie: Honoraria, Other: Travel, Accommodations, Expenses; Janssen: Other: Travel, Accommodations, Expenses. Feugier: Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Astrazeneca: Consultancy, Honoraria. Laribi: AstraZeneca: Other: Personal Fees; Le Mans Hospital: Research Funding; AbbVie: Other: Personal Fees, Research Funding; Jansen: Research Funding; Novartis: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; Takeda: Other: Personal Fees, Research Funding. Tchernonog: JANSSEN: Consultancy; ABBVIE: Consultancy; ASTRAZENECA: Consultancy. Dartigeas: Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress. Quinquenel: Abbvie: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria.

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Thrombosis and Risk of Mortality in Newly Diagnosed High-Risk Polycythemia Vera: An Analysis of the Medicare Claims Database in the United States

Blood ◽

10.1182/blood-2020-141370 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 9-10

Author(s):

Naveen Pemmaraju ◽

Aaron T. Gerds ◽

Shreekant Parasuraman ◽

Jingbo Yu ◽

Anne Shah ◽

...

Keyword(s):

High Risk ◽

Median Time ◽

Research Funding ◽

Index Date ◽

Newly Diagnosed ◽

Publicly Traded ◽

Risk Of Mortality ◽

Increased Risk ◽

History Of

Background Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with an increased risk of thrombotic events (TEs), a major cause of morbidity and mortality. Patients aged ≥60 years and/or with a history of thrombosis are considered to have high-risk PV. There is limited contemporary, real-world evidence exploring the effect of TEs on mortality in patients with PV. The aim of this analysis was to compare the risk of mortality in patients newly diagnosed with high-risk PV who experienced a TE vs those who did not experience a TE. Study Design and Methods All data from the Medicare Fee-for-Service (FFS) claims database (Parts A/B/D) from January 2010-December 2017 were used to identify patients with a PV diagnosis (all high risk based on cohort being ≥65 years of age) with ≥1 inpatient or ≥2 outpatient claims. The index date was the date of the first qualifying PV claim. Patients with a PV diagnosis or use of cytoreductive therapy within 12 months before the index date (pre-index period) were excluded; ≥12-months continuous medical and pharmacy enrollment pre-index dates was required. The study sample was categorized into TE and non-TE groups based on the occurrence of any of the following events during follow-up: deep vein thrombosis, pulmonary embolism, ischemic stroke, acute myocardial infarction, transient ischemic attack, peripheral arterial thrombosis, or superficial thrombophlebitis. TEs were evaluated from the index date to the end of follow-up. Cox regression analyses with time-varying effects were used to assess mortality risk among patients with PV, with post-index TE as a time-dependent variable, stratified by pre-index TE, and adjusting for patient demographic characteristics and comorbid conditions. Results A total of 56,176 Medicare FFS beneficiaries with PV diagnoses met inclusion criteria. The median age was 73 years, 51.9% were men, and 90.7% were white; 10,110 patients (18.0%) had a history of TE before diagnosis (ie, pre-index). In the follow-up period, 20,105 patients (35.8%) had a TE and 36,071 patients (64.2%) did not have a TE. In the comparison between the TE vs non-TE groups, the median (range) age (75.0 [65-104] vs 73.0 [65-106] years, respectively), mean (SD) Charlson comorbidity index score (3.1 [2.6] vs 2.2 [2.3]), and percentage of patients with a history of cardiovascular events (34.1% vs 23.8%), bleeding (13.3% vs 10.4%), or anemia (28.6% vs 23.4%) were higher (Table 1). Among all patients with PV, the median time from diagnosis to first post-index TE was 7.5 months. Among those with pre-index TE (n=10,093), median time from index to first post-index TE was 0.6 months, whereas patients without pre-index TE (n=46,083) had a median time to first post-index TE of 14.2 months. Among all patients with TE during follow-up, the most common TEs were ischemic stroke (47.5%), transient ischemic attack (30.9%), and acute myocardial infarction (30.5%). The risk of mortality was increased for patients who experienced a TE compared with those who did not (hazard ratio [HR; 95% CI], 9.3 [8.4-10.2]; P<0.0001). For patients who experienced a pre-index TE, the risk of mortality was increased for patients who experienced a subsequent TE during follow-up compared with patients who did not (HR [95% CI], 6.7 [5.8-7.8]; P<0.0001). Likewise, for patients who did not experience a pre-index TE, the risk of mortality was increased for patients who experienced a TE during follow-up compared with patients who did not (HR [95% CI], 13.1 [11.4-15.0]; P<0.0001). Conclusions In this real-world study, approximately one-third of patients with newly diagnosed high-risk PV experienced a TE during follow-up and had a 9-fold increased risk of mortality vs those who did not experience a TE. TE risk mitigation remains an important management goal in patients with PV, particularly in those with prior TE. Disclosures Pemmaraju: Samus Therapeutics: Research Funding; Celgene: Honoraria; SagerStrong Foundation: Other: Grant Support; Affymetrix: Other: Grant Support, Research Funding; MustangBio: Honoraria; Blueprint Medicines: Honoraria; LFB Biotechnologies: Honoraria; Plexxikon: Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Stemline Therapeutics: Honoraria, Research Funding; Pacylex Pharmaceuticals: Consultancy; Daiichi Sankyo: Research Funding; Incyte Corporation: Honoraria; Roche Diagnostics: Honoraria; Cellectis: Research Funding; DAVA Oncology: Honoraria. Gerds:Sierra Oncology: Research Funding; Celgene: Consultancy, Research Funding; Gilead Sciences: Research Funding; Imago Biosciences: Research Funding; Pfizer: Research Funding; CTI Biopharma: Consultancy, Research Funding; Roche/Genentech: Research Funding; Apexx Oncology: Consultancy; AstraZeneca/MedImmune: Consultancy; Incyte Corporation: Consultancy, Research Funding. Parasuraman:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Yu:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Shah:Avalere Health: Current Employment. Xi:Incyte Corporation: Other: Avalere Health is a paid consultant of Incyte Corporation; Avalere Health: Current Employment. Kumar:Avalere Health: Current Employment; Incyte Corporation: Other: Avalere Health is a paid consultant of Incyte Corporation. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Verstovsek:Gilead: Research Funding; Incyte Corporation: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; CTI Biopharma Corp: Research Funding; Promedior: Research Funding; Roche: Research Funding; AstraZeneca: Research Funding; Blueprint Medicines Corp: Research Funding; Genentech: Research Funding; Sierra Oncology: Consultancy, Research Funding; Protagonist Therapeutics: Research Funding; ItalPharma: Research Funding; PharmaEssentia: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding.

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Dasatinib or Nilotinib Discontinuation in Chronic Phase (CP)-Chronic Myeloid Leukemia (CML) Patients (pts) with Durably Undetectable BCR-ABL Transcripts: Interim Analysis of the STOP 2G-TKI Study with a Minimum Follow-up of 12 Months – on Behalf of the French CML Group Filmc

Blood ◽

10.1182/blood.v124.21.811.811 ◽

2014 ◽

Vol 124 (21) ◽

pp. 811-811 ◽

Cited By ~ 16

Author(s):

Delphine Rea ◽

Franck E. Nicolini ◽

Michel Tulliez ◽

Philippe Rousselot ◽

Francois Guilhot ◽

...

Keyword(s):

Treatment Duration ◽

Research Funding ◽

Prior History ◽

Molecular Response ◽

Free Survival ◽

Advanced Phase ◽

History Of ◽

Tki Treatment ◽

Tki Discontinuation

Abstract Background: Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have revolutionized the prognosis of pts suffering from CML but these drugs are considered as non-definitively curative and current recommendation is to treat pts during their entire lifespan. However, prospective trials such as STIM, TWISTER and EUROSKI suggest that imatinib may be successfully stopped in pts with deep and sustained molecular responses. Here, we report on the feasibility of second generation TKIs discontinuation in the setting of the French STOP 2G-TKI study. Methods: Adult CP-CML pts on dasatinib or nilotinib first line or after imatinib without prior allogeneic transplantation or progression to advanced phase CML were proposed TKI discontinuation when presenting: (1) b2a2 or b3a2 BCR-ABL transcripts subtype, 2) TKI treatment duration for at least 36 months, (3) CMR4.5 achieved and maintained for at least 24 months. The primary objective was treatment-free survival without loss of major molecular response (MMR). After TKI discontinuation, BCR-ABL transcripts were monitored monthly during the first 12 months, every 3 months during the 2ndyear and every 3 to 6 months thereafter. Molecular relapse was defined by MMR loss on a single occasion and triggered TKI reintroduction. Data as of August 1, 2014 are reported in pts with at least 12 months of follow-up (n=52) and median follow-up was 32 months (12-56). Results: Median age was 60 years (34-81) and 61.5% of pts were female. Sokal risk group was low in 58%, intermediate in 23%, high in 13% and unknown in 6%. 2G-TKIs were given after imatinib intolerance in 67% of pts, suboptimal response or resistance to imatinib in 23% and upfront in 10%. Median duration of CML, TKI treatment, 2G-TKI treatment and CMR4.5 was 83 months (36-218), 78 months (36-136), 39 months (19-72) and 28 months (24-64), respectively. Twenty four pts lost MMR after a median time of 4 months (1-38) at last follow-up. Importantly, no loss of CHR or progression to advanced phase CML was observed. The 12- and 24-month probabilities of treatment-free survival without MMR loss were 61.4% (95% CI, 48.1-74.6) and 57% (95% CI, 43.3-70.6), respectively. The majority of relapses occurred within 6 months and in a landmark analysis, pts who were still in MMR without therapy at 6 months had 12- and 24-month probabilities of treatment-free survival without MMR loss of 91.2% (95% CI, 81.6-100) and 84.7% (95% CI, 72.2-97.1), respectively. All pts but 1 who lost MMR restarted 2G-TKI treatment and regained MMR after a median time of 3 months (1-8). Pts in MMR without any therapy (n=28) displayed varying patterns of spontaneous molecular response including stable CMR4.5 in 7 and fluctuations between CMR4.5 and MR4.5, CMR4.5 and MR4, CMR4.5 and MMR in 9, 4 and 4 pts, respectively. Gender, age, prior interferon exposure, 2G-TKI type, treatment duration and duration of CMR4.5 were not found to have any impact on outcome. By contrast, prior history of suboptimal response or resistance to imatinib was associated with a significantly lower chance of successful treatment discontinuation, with a 12-month probability of treatment-free survival without MMR loss of 41.7% (95% CI; 13.8%-69.6%), compared to 67.3% (95% CI, 52.6%-81.8%) in other patients (p=0.04). Conclusions: 2G-TKI could be safely and successfully discontinued in CP-CML pts with long-lasting undetectable BCR-ABL transcripts, especially in those without prior history of suboptimal response or resistance. Most of molecular relapses had an early onset and all were sensitive to 2G-TKI resumption. The recurrence of low levels of detectable residual disease below MMR after 2G-TKI withdrawal did not automatically herald CML relapse and did not preclude the possibility to remain treatment-free. Disclosures Nicolini: Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Rousselot:Novartis: Research Funding. Gardembas:BMS: Honoraria. Legros:Novartis, BMS: Honoraria. Etienne:Novartis, BMS,Pfizer, ARIAD Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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