Is There an Increase in Sickle Cell Related Events Among the Adult Belgian Population?

Abstract Survival among children and adults with SCD in Belgium published in 2015 showed a low mortality rate (0.25/100 patient years (PY)) among the 469 patients included (5,110 PY) with no significantly increase above 18 years of age. Hydroxyurea (HU) had a positive impact on patients' survival rate when compared to those without disease-modifying treatments (DMT) or transplanted. This led us to compare the incidence of acute complications and hospitalizations among children and adults to see if significant change occurred. Complications before and after the age of 18 for 84 patients with severe genotype followed after 18 years of age and not transplanted for whom the data during childhood were recorded in the registry are detailed in Figure 1 and Table I. Data on the pre- and post-18 years' events for the entire severe genotype cohort are detailed in Table II and include data from the patients under 18 years and data at the pediatric age of those more than 18 years. Data was censored from the time of the transplantation. Furthermore, data from adult patients before age 18 and beyond with severe genotype treated or not with HU are given in Table III. There were 139 patients (1759 PY) more than 18 years who had at last follow up a median age of 21 years (range: 18-53 years). 42% (59/139) of the patients were treated with HU. The median number of vaso-occlusive crisis (VOC) was statistically lower during adulthood (0 vs 29.6/100 PY; p= 0.007) and the median number of acute chest syndrome (ACS) was not statistically higher in adult period compared to their follow-up during childhood. Overall, severe infections as well as hospitalizations number (19 vs 63/100 PY; p=0.0006) and days (119 vs 259/100 PY; p=0.021) are significantly higher in children. The comparison of adults under HU and without DMT showed a significant higher incidence of acute events in HU patients (Table III). This is true for follow-up in childhood and beyond the age of 18 (Table III). Patients without DMT obviously seems to have attenuated symptomatology (clinical phenotype not very severe despite their severe genotype) and were therefore not considered benefiting from DMT. In the latter, no ACS was recorded during their follow-up in adulthood (Table III). The increase in CVO and ACS incidence with age is well described in the literature but not found in our results. Higher number of hospitalizations and infections before 18 years of age are observed. This can be explained by the fact that children consult more quickly and frequently and they are more readily monitored in hospital compared to adults. They also live in community, which increases the risk of seasonal viral infections. Compared with data available in the literature, our adult patients, most of whom are treated with HU, have fewer acute complications. Nevertheless the comparison is jeopardized because of different methodological approaches. In addition, our cohort of adult patients is limited, has a relatively short follow-up and consists mainly of adults under 21 at the last follow-up. The shorter length of follow up and the underrepresentation of older adults who pay a heavier toll on SCD because of co-existence of chronic complications, may explain the reduced incidence of acute complications in our cohort. In conclusion, the incidence of events observed in our adult population is lower than that described in the literature. This difference is probably related to a larger proportion of HU patients in our cohort. But these results should be confirmed by data from a larger number of adult patients with longer prospective follow-up. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Abstract TP366: Significant Reduction in Readmission Using Transitions Nurse

Stroke ◽

10.1161/str.51.suppl_1.tp366 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Kiersten Espaillat ◽

Paula Buckner

Keyword(s):

Hospital Discharge ◽

Transitional Care ◽

Medical Center ◽

Hospital Readmissions ◽

Primary Diagnosis ◽

Adult Patients ◽

Care Coordinator ◽

Readmission Rates ◽

Before And After

In an effort to reduce early hospital readmissions, Vanderbilt University Medical Center (VUMC) implemented a transitional care coordinator (TCC) to provide careful coordinated follow up care for stroke patients after hospital discharge. The aim of this study is to compare all cause thirty- day readmission rates of adult patients with a primary diagnosis of stroke before and after the implementation of a stroke services TCC. All adult patients admitted to VUMC with a primary diagnosis of stroke; ischemic, hemorrhagic, and TIA; and readmitted within the first thirty days following hospital discharge between January-June of 2015, 2016, 2017, & 2018 were analyzed. Readmission data from 2015 & 2016, prior to the implementation of the TCC was compared to readmission data from 2017 & 2018, after the TCC was implemented. A total of 1911 charts were reviewed for the timeframe January-June of 2015-2018. In 2015 there were 369 stroke admissions and 120 (33%) were readmitted and in 2016 there were 474 stroke admissions and 112 (24%) readmissions, before the TCC role was implemented. In 2017 there were 540 stroke admissions and 62 (11%) were readmitted and in 2018 there were 528 stroke admissions and 74 (14%) readmissions, after the TCC role was implemented. Hospital readmissions were reduced significantly after implementing a TCC.

Download Full-text

A Phase II Study of Decitabine In Advanced Chronic Myelomonocytic Leukemia (CMML)

Blood ◽

10.1182/blood.v116.21.1873.1873 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1873-1873

Author(s):

Thorsten Braun ◽

Nathalie Droin ◽

Benoit de Renzis ◽

Francois Dreyfus ◽

Kamel Laribi ◽

...

Keyword(s):

Phase Ii ◽

Conflicts Of Interest ◽

Cytogenetic Response ◽

Median Number ◽

Costal Margin ◽

Monocyte Count ◽

Blood Monocytes ◽

Grade 3 ◽

Wbc Count

Abstract Abstract 1873 Background: CMML, now classified among MDS/MPN, is prognostically heterogeneous. We (JCO 1988 6:1417, Blood 1996 88:2480) and others found prognosis in CMML to depend on both “MDS factors” (% marrow blasts, cytopenias, karyotype) and “MPN” factors, ie splenomegaly (SMG), WBC count, extramedullary disease (EMD). Treatment of advanced CMML is difficult. The hypomethylating agents Azacitidine and Decitabine (DAC) have shown efficacy in CMML, but in prognostically heterogeneous cohorts. We conducted a phase II trial of DAC in a well defined cohort of advanced CMML. Methods: To be included, CMML (according to WHO) should have: if WBC<13G/l an IPSS≥1.5; if WBC≥13G/l, two of the following criteria: marrow blasts≥5%, Hb<10g/dl, plts<100G/l, abnormal cytogenetics, SMG >5cm below costal margin, (SMG>5cm), EMD, based on our previous prognostic factors. Pts received DAC 20mg/m2/d IV for 5 days every 28 days for at least 3 cycles. Response criteria were based on IWG 2006 for pts with WBC <13G/L and for pts with WBC > 13 G/L also included evolution of WBC, SMG and EMD (Blood 1996 88:2480). Results: Between Nov 2008 and June 2009, 41 pts were included in 16 centers, of whom 39 completed at least one cycle and were considered evaluable for response (the 2 other pts died from septic shock before and during the first cycle respectively). Median number of cycles was 9 (range 1–17). Median age was 71 years (range 54–88), M/F:30/9. Seventeen pts had CMML 1 and 22 had CMML 2 (including pts with up to 29% marrow blasts). Median WBC count was 29.5G/l (range 4.1–147.3), median blood monocytes 3G/l (range 1.05–95.7), and median BM blasts 10% (1-29). Nine pts had WBC<13G/l and 30 WBC≥13G/l. Abnormal karyotype was found in 18 (46.2%) pts, including +8 and -7 in 7 and 1 case, respectively. 15 pts (38.6%) had SMG>5cm and 8 (20.5%) EMD involving skin (n=5) and lymph nodes (n=3). Overall Response Rate (ORR,) was 38.6% with 4 (10.3%) CR, 8 (20.5%) marrow CR and 3 (7.7%) Stable Disease (SD) with HI. 1 CR pt received allo SCT. 18 (46%) pts had SD without HI and 6 (15.4%) pts progressed to AML. 8 (36.4%) of the 22 RBC transfused pts became RBC transfusion independent. 3/10 (30%) pts with plt<50G/l reached plt>100G/l. Four pts had cytogenetic response (3 CR and 1 PR) exclusively among pts with +8. Median peripheral monocyte count decreased from 4.8G/l to 0.3G/l after 3 cycles of DAC among responders. SMG disappeared in 6/15 (40%) pts and EMD in 6/8 (75%) pts. 16 pts were receiving Hydroxyurea (HY) at inclusion which could be stopped in 12 of them. With a median follow up of 10 months (1-18), 7 pts had died from progression (n=3), sepsis (n=3) and unrelated cause (n=1). Overall Survival (OS) estimate was 60% at 2 years (median not reached). By comparison, in our previous trial of HY in CMML where inclusion criteria were the same, 2 year survival was 43% (median OS 20 months; Blood 1996 88:2480), for a median follow up of 11 months (range1-43). The only factor associated with response to DAC was WHO subtype, CMML 2 pts showing significantly better ORR (30.8% vs 7.7% in CMML 1; p=0.041).There was no difference in survival between CMML 1 and 2 pts. Treatment with DAC was generally well tolerated with, except for usual grade 3/4 cytopenias, and grade 3 fatigue (n=1). Conclusion: DAC is active in advanced CMML and safe in these elderly pts. A possibly better survival than with HY will have to be confirmed in randomized trials. Correlative genetic studies identifying markers potentially predicting response and survival for DAC are currently underway in our lab. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Allogeneic Stem Cell Tranplantation (allo-SCT) for Adult Patients with Active Refractory/Relapsed Hematological Malignancies: a Survey From the Societe Française De Greffe De Moelle Et De Therapie Cellulaire (SFGM-TC).

Blood ◽

10.1182/blood.v116.21.3456.3456 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3456-3456

Author(s):

Patrice Chevallier ◽

Noel Milpied ◽

Karin Bilger ◽

Gérard Socié ◽

Ibrahim Yakoub-Agha ◽

...

Keyword(s):

Stem Cell ◽

Conflicts Of Interest ◽

Phase 1 ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Best Supportive Care ◽

Adult Patients ◽

Peripheral Blood Stem Cells ◽

Hematological Diseases

Abstract Abstract 3456 Patients with active refractory/relapsed hematological diseases have a very poor outcome. Best supportive care or investigational therapies in phase 1 trials are usually proposed to these patients. However, some previous data suggested that allo-SCT might be an efficient therapy even in the setting of chemorefractory disease, because long-term immune-mediated disease control can be achieved in some patients after allo-SCT. The aim of this study was to evaluate on a large series the outcome of adult patients with active refractory/relapsed hematological diseases at time of allo-SCT and to determine which sub-group would most benefit from such approach. Between 2005 and 2009, 861 patients with various hematological diseases (AML, n=323; ALL, n=43; MDS, n=129, CMML, n=12; MPS, n=110; CML, n=28; NHL, n=100; HL, n=40; myeloma, n=36; CLL, n=24; and other, n=16) were treated with allo-SCT, and reported to the SFGM-TC Registry. Per study criteria, all patients presented with active refractory or relapsed disease at time of transplant. This series included 517 males (60%) and 344 females (40%). The median age at transplant was 50 (range, 16–71) years. The median interval between diagnosis and transplant was 17 (range, 1–99) months. 32% of patients failed at least one prior SCT (Autologous or allogeneic prior to allo-SCT). 350 (41%) patients received allo-SCT from an HLA-matched sibling donor, while the remaining 59% received an allogeneic graft from a matched unrelated or mismatched donor. The stem cell source was mainly peripheral blood stem cells (n=617; 72%). Bone marrow was used in 139 patients (16%), and cord blood in 107 patients (12%). Myeloablative conditioning regimen was used in 328 patients (38%), and various reduced-intensity regimens were used in other cases (62%). With a median follow-up of 290 (range, 1–1854) days after allo-SCT, engraftment was observed in 88% of cases. Grade II-IV and grade III-IV acute GVHD occurred in 35% (n=301) and 17% (n=144) of patients, respectively. Chronic GVHD was observed in 185 patients (21%; limited: n=77; extensive: n=82; missing data: n=24). At last follow-up, 347 patients (40%) were still alive (of whom 297 were in CR; 86%). 246 patients (28.5%) died of disease progression, and 232 patients died of transplant-related causes (NRM: 27%). The Kaplan-Meier (KM) estimates of overall survival (OS) at one and 2 years were 39% (95%CI, 36–43%) and 31% (95%CI, 28–35%), respectively. Of note, in patients with lymphoma (n=140), OS at 1 and 2 years were 57% (95%CI, 48–66%) and 49% (95%CI, 40–58%) versus 36% (95%CI, 32–40%) and 27% (95%CI, 23–31%), respectively, in all other diagnoses (P=0.00004). In a Cox multivariate analysis accounting for relevant factors, a diagnosis of lymphoma (NHL or Hodgkin) was the most significant factor associated with improved survival (RR=1.68; 95%CI, 1.3–2.2; P=0.0001). Despite its retrospective nature and the inherent selection biases, in case of availability of suitable donor, this data support the use of allo-SCT in adult patients with active refractory/relapsed hematological diseases, especially in patients with lymphomas. Results are expected to be further improved with the advent of novel conditioning regimens and maintenance therapies after transplant that are currently tested as part of prospective studies. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Busulfan (Bu) Plus Cyclophosphamide (Cy) Versus TBI Plus Cy Conditioning for Allogeneic Stem Cell Transplantation (alloSCT) From Matched Unrelated Donors (MUD) In Adult Patients with AML in First Relapse: A Survey From the Acute Leukemia Working Party of EBMT

Blood ◽

10.1182/blood.v118.21.161.161 ◽

2011 ◽

Vol 118 (21) ◽

pp. 161-161 ◽

Cited By ~ 1

Author(s):

Arnon Nagler ◽

Myriam Labopin ◽

Avichai Shimoni ◽

Jürgen Finke ◽

Dietrich Beelen ◽

...

Keyword(s):

Acute Gvhd ◽

Conflicts Of Interest ◽

Working Party ◽

Risk Groups ◽

Adult Patients ◽

Free Survival ◽

Unrelated Donors ◽

Conditioning Regimens ◽

First Relapse

Abstract Abstract 161 TBY/Cy and Bu/Cy are the standard myeloablative conditioning regimens for alloSCT in adults with AML. Whether, one is associated with better outcomes compared to the other in the setting of relapsed AML is not well described. We therefore compared TBI/Cy to Bu/Cy conditioning prior to alloSCT in 158 adult patients (pts) with AML in first relapse (Rel 1) that underwent alloSCT from HLA matched (6/6) unrelated donors. 83 patients were given TBI/Cy and 75 Bu/Cy. The median age was 38 years (range, 19–62) in the TBI/Cy vs. 42 years (19–72) in the Bu/Cy group (P<0.012). FAB classifications, cytogenetic risk, time from diagnosis to alloSCT, donor gender and CMV serostatus were not different between the 2 groups. Median year of alloSCT was 2004 vs. 2007 (P<0.0001) for the TBI/Cy vs. Bu/Cy groups, respectively. Conditioning included ATG in 31% vs. 67% in the TBI/Cy and Bu/Cy groups, respectively (P<0.001). 78% of the Bu/Cy group and 80% of the TBI/Cy group, received PBSC grafts, while 22% and 20% received BM grafts, respectively (P=0.8). Median follow-up was, 23 months (range, 1–125) in TBI/Cy and 21 months (1–119) in Bu/Cy. The engraftment rate was similar between both groups with ANC>500/μL achieved at a median of 17 (10–33) and 16 (6–31) days in the TBI/Cy and Bu/Cy groups, respectively (P=0.23). Similarly, acute GVHD (≥Gr II) incidence did not differ between the 2 groups: 33% vs. 37% for the TBI/Cy vs. Bu/Cy, respectively. Death before day 100 occurred in 38% vs. 25% with TBI/Cy vs. Bu/Cy, respectively (P=0.25). 2- year NRM was similar between the 2 groups, 31±5% vs. 21±5%, respectively (P=0.15). In addition, the 2-year relapse rate did not differ between the 2 groups: 50±4% vs. 50±6%, respectively (P=0.93). Leukemia-free survival (LFS) at 2 years, was also similar between the TBI/Cy vs. Bu/Cy groups: 18 ± 5% vs. 29 ± 6 %, respectively (P=0.10). However, overall survival (OS) was significantly higher with Bu/Cy vs. TBI/Cy 38±6% vs. 21±4%, respectively (P=0.02). The main cause of death was disease relapse: 53% and 60%, with TBI/Cy vs. Bu/Cy, respectively (p=0.49). Of note, there were no differences in death from organ toxicities including VOD between the 2 groups. The rate of infection-related deaths did not differ between the groups, as well, 19% vs. 11% (p=0.25). In multivariate analysis, age, cytogenetic risk groups, use of ATG and interval from diagnosis to alloSCT were not significant prognostic factors for survival. In all, these results suggest that in AML patients in Rel 1 undergoing myeloablative alloSCT, Bu/Cy and TBI/Cy conditioning regimens can lead to similar outcomes including GVHD, NRM, disease progression and LFS. However, in terms of OS, there is a suggestion for an advantage in favor of the Bu/Cy regimen possibly due to a lower overall toxicity and improved capacity for salvage therapy. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Biphenotypic Blast Phase (B-BP) of Chronic Myeloid Leukemia (CML): A Single Institution Experience

Blood ◽

10.1182/blood.v120.21.1687.1687 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1687-1687

Author(s):

Hady Ghanem ◽

Hagop M. Kantarjian ◽

Elias Jabbour ◽

Lakshmikanth Katragadda ◽

Jorge E. Cortes ◽

...

Keyword(s):

Bone Marrow ◽

Kinase Inhibitor ◽

Conflicts Of Interest ◽

Chronic Phase ◽

Median Number ◽

Cancer Center ◽

Molecular Characteristics ◽

Blast Phase ◽

Extramedullary Disease

Abstract Abstract 1687 Approximately two thirds of patients with CML BP exhibit a myeloid phenotype, and one third a lymphoid phenotype. In rare occasions, patients exhibit a mixed phenotype. Biphenotypic blast phase (Bi-BP) are rare and generally portend a very unfavorable prognosis. To evaluate the incidence and outcome of Bi-BP, we reviewed 1143 patients with CML BP diagnosed and treated at M.D. Anderson Cancer Center between November 1973 and February 2012. Only Bi-BP with both myeloid and B-lymphoid differentiation was included in this analysis. Twelve (1%) patients had Bi-BP. At presentation, the median age was 62 years (range, 29–81), WBC count 12×109/L (range, 6–214), hemoglobin 10 g/dL (range, 7–14), platelet count 94×109/L (range, 41–531), peripheral blood blasts 30% (range, 0–83), and bone marrow blasts 66% (range, 0–91). Five (42%) patients had extramedullary disease involving the central nervous system (CNS; n=2), lymph nodes (n=2), and CNS, orbit and skin without bone marrow disease (n=1) (Table 1). The median time from diagnosis to transformation was 15 months (range, 0–58). Six patients expressed a b2a2 BCR-ABL1 transcript (p210), whereas 4 patients expressed b3a2 (p210) and in 2 patients such information was not available. Three patients presented initially with BP and 9 evolved to BP from chronic phase (CP). Out those 9, 6 had failed imatinib, 3 interferon, 1 dasatinib, 1 ara-C and 1 hydroxyurea prior to transformation. Median number of treatments prior to BP was 1 (range, 1 to 3). Initial therapy for Bi-BP was hyper-CVAD in 2 patients, one of them achieving complete cytogenetic remission (CCyR); hyper-CVAD and dasatinib in 1 patient, achieving a marrow CR; idarubicin, ara-C, and imatinib followed by allogeneic stem cell transplantation in 1 patient, with no response; idarubicin, ara-C, vincristine and dexamethasone in 1 patient, achieving CCyR; troxicitabine in 1 patient, achieving CCyR; combination of decitabine and imatinib in 1 patient, achieving CCyR; azacitidine and valproic acid in 1 patient with no response; and imatinib with homoharrangtonine in 1 patient with no response. Overall, 5 patients responded, to a variety of chemotherapy regimens that included a tyrosine kinase inhibitor in 2 of them. Median duration of response was 7 months (range, 1–55). One patient died during induction chemotherapy. A total of 5 patients received subsequent therapy: TKI in 3 patients and allogeneic SCT in 2 patients. Three patients developed BCR-ABL1 gene mutations: Y253H (n=1), T315I (n=1), and F317L & V299L (n=1). At last follow up, 10 patients were dead (5 due to progression) and 2 were lost to follow up. In conclusion, Bi-BP is a rare entity, which frequently exhibits an aggressive course, extramedullary disease, and high resistance to conventional chemotherapy. Therapy requires the use of chemotherapy in combination with a TKI. Nevertheless, responses are short-lived and patients should be offered allogeneic SCT or novel investigational approaches. Table 1. Summary of patients' clinical and molecular characteristics, response to treatments and outcomes Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Erlotinib Is Not Effective In Patients (Pts) With JAK-2 V617F Positive Polycythemia Vera

Blood ◽

10.1182/blood.v122.21.1597.1597 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1597-1597

Author(s):

Mohamad Cherry ◽

Mohamad Khawandanah ◽

Zhizhuang Joe Zhao ◽

Samer A Srour ◽

Howard Ozer ◽

...

Keyword(s):

Polycythemia Vera ◽

Conflicts Of Interest ◽

Growth Factor Receptor ◽

Median Number ◽

Preclinical Study ◽

Spleen Size ◽

University Of Oklahoma ◽

Grade 3

Abstract Introduction Erlotinib is an epidermal growth factor receptor small-molecule inhibitor and is FDA approved for the treatment of lung and pancreatic cancers. In preclinical study, in vitro colony culture assays revealed that erlotinib at micro-molar concentrations effectively suppressed the growth and expansion of Polycythemia Vera (PV) hematopoietic progenitor cells while having little effect on normal cells. Several JAK inhibitors are being studied for the management of PV, one of which has been approved for the treatment of myelofibrosis (ruxolitinib). Aim To study the clinical effect of erlotinib in pts diagnosed with JAK2V617F + PV. Methods We conducted a single arm, prospective phase II study at the University of Oklahoma and the Oklahoma City VA hospitals in pts with WHO defined JAK-2 V617F positive PV from June 2010 to August 2012. Appropriate IRB approval was obtained in accordance with Hilsinki declaration. Pts had to be requiring phlebotomy. Toxicity was assessed by treating physicians using NCI version 4. Dose modification for erlotinib was done using label recommendations. Results Five Caucasian pts were enrolled (3 (60%) males, with median age at enrollment of 63 years, range 26-79). Pts had pretreatment median hemoglobin14.4 g/dL (10.4 -19.2 g/dL), median platelet count 511 x109 (424-681 x109), median white blood cell (WBC) 14.4 x109(7.8- 18.3 x109). Three pts had splenomegaly prior to treatment. Median number of prior pharmacologic treatments (hydroxyurea, anagralide or interferon) was 1, range 0-2. Pts were given erlotinib 150 mg orally daily for 16 weeks: responders (phlebotomy free or decrease in spleen size) were allowed to continue a total of 1 year of treatment, while non-responders were taken off the study. Three (60%) patients received therapy for 16 weeks and did not achieve hematological response or improvement in spleen size. Two (40%) pts were taken off the study after 2 doses secondary to severe toxicities (grade 3 colitis in 1 case, and grade 3 facial rash in 1case). No therapy continued beyond 16 weeks (due to toxicity or lack of response). All pts in the study developed rash (grade 1 – 3) and diarrhea (grade 1 – 2). Three pts developed mucositis (see Table 1). No death was observed during the study and follow up period (median follow up was 23 months, range 12-37 months). Study was closed due to lack of efficacy. Conclusions Despite in vitro efficacy of erlotinib as potent inhibitor of JAK-2 activity, erlotinib is not effective in pts with JAK-2 V617F positive PV with poor toxicity profile. Poor accrual was related to potential toxicity of erlotinib compared to alternative treatments in view of lack of clinical efficacy. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Carfilzomib-Pomalidomide-Dexamethasone (KPD) in Relapsed/Refractory Multiple Myeloma Patients - an Institutional Retrospective Analysis

Blood ◽

10.1182/blood-2019-131674 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5572-5572

Author(s):

Pallavi Mehta ◽

Neha Yadav ◽

Mohan Bhaarat ◽

Sumeet Prakash Mirgh ◽

Vishvdeep Khushoo ◽

...

Keyword(s):

Multiple Myeloma ◽

Maintenance Therapy ◽

Progressive Disease ◽

Conflicts Of Interest ◽

Haematological Toxicity ◽

Response Assessment ◽

Median Number ◽

Entire Cohort ◽

Response Status

Introduction Multiple myeloma has relished the emergence of various novel agents in last few decades. Unfortunately,relapses are still an inevitable part and at each relapse, treatment choice becomes a complex decision making process as these patients usually have exhausted conventional therapeutic regimens.Carfilzomib is a second-in class Proteosome Inhibitor (PI) and has been approved for patientsrefractory to minimum 2 lines of prior therapies. We are, hereby, presenting our initial experience with this novel combination (KPD)in RRMM patients at our centre. Methodology Retrospective study of RRMM patients who received KPD therapy from August 2017 till October 2018. Responses were assessed as per International Myeloma Working Group. Study was approved by Institutional Review Board. Results Total 39 patients were treated with KPD regimen during study period. Median age was 56 (32-74 years) with male ratio of 51.2% (n=20). At baseline presentation, bone disease {n=32 (82%)} was the most common presenting complaint followed by anemia {n=21 (53.8%)} and renal failure {n=16 (41%)}. Most common ISS staging was ISS-3 {n=18(46.1%)} and subtype was Light chain myeloma {n=15 (38.3%)} followed by IgG {n=13 (33.3%)}.Fluorescence In Situ Hybridization (FISH) was available in {n= 10 (25%)} and it was positive for del13q (n=1/10) and del17p (n=1/10) and t(11;14) (n=1/10). (Table-1) Median number of prior lines of chemotherapy was 3(1-15). Thirty-six (91%) patients were relapsed/refractory to both bortezomib and lenalidomide whereas n=3(9%) were relapsed/refractory to bortezomib only. Eleven (30.5%) patients underwent SCT pre KPD therapy including 2/11 patients received double SCT. Pre KPD 25 (64.1%) patients had progressive disease (PD), 10 (25%) had relapse and 4 (11.1%) patients had stable disease (SD). Median number of KPD cycles were 3(1-8). Median number of KPD cycles after which response assessment was donewas 3 (2-8). Median time to treatment response was 3 (2-7) months. ORR was 51.2% {CR-n=5 (12.8%); VGPR-n=5 (12.8%), PR-n=10 (25.6%)} whereas 2 (5.1%) patient had SD and 10 (25.6%) patients had PD at 2-8 cycles. Two (5.1%) patients are yet to be assessed. (Table-1) Common hematological toxicities seen were anemia (n=8), thrombocytopenia (n=13){grade-3/4=30.7%; n=4/13} and neutropenia(n=14){grade3/4=21.4%; n=3/14}.Non haematological toxicity such as cardiac toxicity was not observed in our patients. Pre KPD 2D-ECHO was available for 13 patients and which was normal in all patients. Post 2-4 cycles of KPD, 2D-ECHO was available for 7 patients and all patients had normal ECHO. Carfilzomib induced hypertension was seen in 20 patientsand could be well controlled with antihypertensives. Peripheral neuropathy (grade1/2) was seen in 10 patients. We also observedCarfilzomib induced hyponatremia in one patient.Febrile neutropenia(bacterial =6, viral=4, possible fungal=5) was seen in 14 patients.(Table-2) Twelve (20.5%) patients proceeded to either maintenance therapy or autologous stem cell transplantation (ASCT). Eight patients opted only for maintenance (carfilzomib=5, pomalidomide-dexamethasone=2 and pomalidomide =1). Remaining n=4/12(16%) patients received SCT. Pre SCT response status was VGPR n=2; PR n=1 and SD=1. Post SCT response status was VGPR (n=3) &PR (n=1). Post SCT, 3 patients were started on maintenance therapy as Bortezomib/pomalidomide=1, Pomalidomide/dexamethasone=2. One patient has been continued on KPD as a consolidation therapy. At a median follow-up of 10 months (1-14 months), relapse rate was 12.8% (n=5). Ten (25.6%) patients had PD.Mortality rate was 8.3% (n=3), commonest cause being progressive disease. The estimated mean PFS, OS and EFS of entire cohort was 11.9 months (95% C.I. 10.8- 13 months) (figure-1 a), 13 months (95% C.I. 11.9-14 months) (figure-1 b) and 7.9 months (95% C.I. 6.5-9.3 months) (figure - 1 c) respectively. Conclusion KPD is a well-tolerated regimen for patients with RRMM who have exhausted frontline myeloma regimen, however at the cost of significant side effects like infections and hypertension. It seems to be a convincing regimen as a bridge to ASCT but warrants further studies with longer follow-up to validate our results. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Retrospective Analysis of Adults with Acute Myeloid Leukemia Treated with Venetoclax Plus Hypomethylating Agents at a Comprehensive Cancer Center

Blood ◽

10.1182/blood-2018-99-119593 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1424-1424 ◽

Cited By ~ 1

Author(s):

Matthew Tenold ◽

Benjamin Moskoff ◽

David Benjamin ◽

Brian A. Jonas

Keyword(s):

Research Funding ◽

De Novo ◽

Response Rates ◽

Median Number ◽

Adult Patients ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Hypomethylating Agents ◽

De Novo Aml

Abstract Introduction Venetoclax (VEN) is a potent B-cell lymphoma 2 (BCL-2) inhibitor and demonstrates synergistic anti-AML activity when used in combination with hypomethylating agents (HMA) such as azacitidine (AZA) and decitabine (DEC). This regimen has demonstrated high response rates and durable activity in treatment naïve (TN) older patients; however, the efficacy in relapsed and/or refractory (R/R) AML is less well characterized, with one study showing a response rate of 21%. To further characterize VEN plus HMA activity in these populations, we retrospectively reviewed the outcomes of both TN and R/R AML patients treated with VEN plus HMA at the University of California Davis Comprehensive Cancer Center (UCDCCC). Methods Adult patients (≥18 years) with an acute leukemia treated with VEN off protocol between January 1, 2014 through June 22, 2018 were included. Under an IRB-approved protocol, patients were retrospectively reviewed using an electronic medical record generated report. Baseline data included patient demographics, performance status, disease characteristics, prior chemotherapy, bone marrow biopsy studies and labs. Regimen data included other chemotherapy agents received, VEN dose and modifications, antifungal prophylaxis (ppx), and granulocyte colony stimulating factor (GCSF) use. Efficacy outcomes included complete remission (CR), CR with incomplete count recovery (CRi), composite CR (cCR, defined as CR + CRi), morphologic leukemia free state (MLFS), overall leukemia response (OLR, defined as cCR + MLFS), overall survival (OS), and relapse free survival (RFS). Toxicity outcomes were reviewed, including tumor lysis syndrome (TLS), febrile neutropenia (FN), and prolonged pancytopenia. All follow-up clinic visits, hospitalizations and deaths were reviewed. Results Forty-two patients were included (AML, n=41; acute undifferentiated leukemia, n=1). Median age was 67 years [25-88] and 67% were male. Eighteen (43%) had de novo AML, 17 (40%) had preceding myelodysplastic syndrome (MDS), 4 had MDS/myeloproliferative neoplasm (MPN) (10%) and 3 (7%) had primary myelofibrosis. Sixteen were TN (38%), thirteen (31%) had relapsed disease, and 13 (31%) had refractory disease. Median number of prior regimens was 1 [0-6]. Thirty-seven (88%) had an ECOG of 0 to 1 [0-3]. ELN genetic risk classification was intermediate in 19 (45%) and adverse in 22 (52%). VEN was combined with AZA in 12 (29%) and DEC in 30 (71%). Median VEN dose was 400 mg [50-800 mg]. Median follow-up was 17.2 months. For the entire study, the cCR was 43% and the OLR was 57%. See table 1 for cCR and OLR for subgroups including previously untreated, R/R, de novo, secondary AML (sAML), and various molecular and cytogenetic subgroups. Median OS was 6.2 months (Figure 1). For patients with cCR, OLR, and MLFS, median survival was 21.6, 15.1, and 4.9 months respectively (Figure 2). Median OS and median OS in responders for patients with de novo AML, sAML, untreated patients, and R/R patients is shown in Figure 3, Figure 4, and Table 1. Median number of cycles for cCR was 1 [1-6]. Of patients who obtained cCR, 6 (33%) experienced relapse of AML. Median time to relapse was 6.6 [3.4-13.9] months. Eight (19%) patients were bridged to allotransplant. Lab TLS occurred in 1 patient. Seventeen (40%) experienced prolonged pancytopenia. Eighteen (43%) had FN and 4 (22%) received GCSF. Antifungal ppx was used in 41 (98%) patients: micafungin in 17 (40%) and a non-fluconazole azole in 24 (57%). Seven (17%), of which 5 (71%) had R/R AML, were diagnosed with a fungal infection; 5 (71%) were receiving ppx azoles and 2 (29%) micafungin. Three and 6 died within 30 and 60 days of therapy initiation, respectively; all 3 patients who died within 30 days had R/R AML. The most common cause of death was refractory AML at 14 (52%) followed by infection in 9 (33%). Conclusion At UCDCCC, VEN in combination with an HMA is well tolerated and produces high rates of response in adult patients with AML. Response rates for TN AML, sAML and multiple molecular subgroups are consistent with prior reports, while higher than expected response rates and survival were seen in R/R AML. Responses were also seen in post-MDS/MPN and post-MF patients. In extended follow-up, survival has been durable in patients with cCR, but not MLFS. The use of VEN plus HMA combinations in adults with AML represents a viable treatment option for both TN and R/R AML. Disclosures Jonas: AbbVie: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; Genentech/Roche: Research Funding; Glycomimetics: Research Funding; Pharmacyclics: Research Funding; Tolero: Consultancy; Amgen: Consultancy; Forma: Research Funding; Incyte: Research Funding; Esanex: Research Funding; Kalobios: Research Funding; Accelerated Medical Diagnostics: Research Funding; LP Therapeutics: Research Funding.

Download Full-text

Optimization of Medication Regimens in Patients with Type 2 Diabetes and Clinical Atherosclerotic Cardiovascular Disease

Pharmacy ◽

10.3390/pharmacy9040186 ◽

2021 ◽

Vol 9 (4) ◽

pp. 186

Author(s):

Jarred Prudencio ◽

Paige Cajudoy ◽

Donald Waddell

Keyword(s):

Cardiovascular Disease ◽

Positive Impact ◽

Atherosclerotic Cardiovascular Disease ◽

Medication Usage ◽

Pharmacist Interventions ◽

Before And After ◽

Prescription Rates ◽

Lost To Follow Up

The American Diabetes Association recommends that patients with type II diabetes and atherosclerotic cardiovascular disease be prescribed an SGLT-2 inhibitor or GLP-1 agonist for cardioprotective benefit. This project assessed the use of these medications in this patient population in a rural clinic by measuring prescribing rates of SGLT-2/GLP-1 therapy before and after pharmacist interventions. Of the 60 patients identified at baseline, 39.39% (13/33) managed by a pharmacist were prescribed SGLT-2/GLP-1 therapy compared to the 14.81% (4/27) who had not seen a pharmacist (p = 0.025). Of the 43 patients that were not on SGLT-2/GLP-1 therapy at baseline, 13 were lost to follow-up and 13 had contraindications. For the 17 remaining patients, pharmacists recommended initiating SGLT-2/GLP-1 therapy and were able to successfully initiate therapy for 9 patients (52.94%). Pharmacist interventions improved the prescription rates from a baseline of 36.17% (17/47) to 55.3% (26/47) (p = 0.002), with SGLT-2/GLP-1 therapy contraindicated in 27.66% (13/47) of patients. This suggests that patients managed by a pharmacist have medication regimens that were optimized at a greater rate and pharmacists can have a positive impact on the appropriate medication usage in this population.

Download Full-text

PS01.051: EFFICACY OF 20-MG VONOPRAZAN ON-DEMAND THERAPY AS A MAINTENANCE THERAPY FOR PATIENTS WITH MILD REFLUX ESOPHAGITIS

Diseases of the Esophagus ◽

10.1093/dote/doy089.ps01.051 ◽

2018 ◽

Vol 31 (Supplement_1) ◽

pp. 64-64

Author(s):

Tomohide Tanabe ◽

Noriyuki Kawami ◽

Shintaro Hoshino ◽

Yoshimasa Hoshikawa ◽

Takenouchi Nana ◽

...

Keyword(s):

Maintenance Therapy ◽

Scale Score ◽

Conflicts Of Interest ◽

Gastrin Level ◽

On Demand ◽

Level Of Satisfaction ◽

Endoscopic Remission ◽

Before And After ◽

Disease Grade

Abstract Background The aim of this study is to investigate the efficacy of on-demand therapy with 20-mg Vonoprazan (VPZ) as a maintenance therapy for patients with mild RE. Methods On-demand therapy of orally taking one 20-mg tablet of VPZ only when reflux symptoms occurred was carried out in 30 patients with mild RE who were in a state of endoscopic remission on maintenance therapy using PPI and answered ‘very satisfied’ or ‘satisfied’ to an overall satisfaction survey. Patients who were remission on 24 weeks after the initiation of on-demand therapy continued the on-demand therapy for a total of 48 weeks. RE symptoms were assessed at 24 and 48 weeks after the initiation of on-demand therapy. Patient satisfaction, symptoms (F-scale), and gastrin level before breakfast were compared before and after the on-demand therapy. In addition, the number of VPZ tablets taken and the frequency (regular, temporary, rare) of its administration were examined. Results One of the 30 patients dropped out of on-demand therapy 1 week after its initiation. At the 24-week follow-up, recurrence of RE was found in 13.8% of the patients. There were no significant differences in the level of the F-scale score, overall level of satisfaction, and gastrin level before and after the on-demand therapy. During the 24-week on-demand therapy, patients took 33 (median) VPZ tablets. 31.0% of the patients took VPZ on a regular basis (at least 2 tablets a week); the remaining patients took VPZ on a temporary or rare basis. After additional 24 weeks, 21 of 25 patients who maintained remission completed the 48-week study. 15.4% had recurrent disease (grade A and B). There were no significant differences in the F-scale score, overall level of satisfaction, and gastrin level before and 48 weeks after the on-demand therapy. At the end of the 48-week on-demand therapy, patients had taken 69 VPZ tablets, and 42.9% of the patients took VPZ on a regular basis. Conclusion Discussion: On-demand therapy with 20-mg VPZ is an effective alternative for PPI maintenance therapy for mild RE. Disclosure All authors have declared no conflicts of interest.

Download Full-text