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Relapse after stem cell transplantation for Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) remains a significant challenge. In this systematic review, we compare survival outcomes of second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib with first-generation TKI imatinib when these agents are used after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Ph+ ALL. In addition, we review the literature on TKI use to prevent relapse in patients who proceed to allo-HSCT beyond first complete response (>CR1). We performed database searches (inception to January 2018) using PubMed, Cochrane Library, and Embase. After exclusions, 17 articles were included in this analysis. Imatinib was used post-transplant either prophylactically or preemptively in 12 studies, 7 prospective studies and 5 retrospective studies. Overall survival (OS) for most prospective studies at 1.5 to 3 and 5 years ranged between 62% to 92% and 74.5% to 86.7%. Disease-free survival at 1.5 to 5 years was 60.4% to 92%. Additionally, imatinib failed to show survival benefit in patients who were >CR1 at the time of allo-HSCT. The cumulative OS for most retrospective studies using imatinib at 1 to 2 and 3 to 5 years was 42% to 100% and 33% to 40% respectively. Event-free survival at 1 to 2 and 3 to 5 years was 33.3% to 67% and 20% to 31% respectively. Dasatinib was used as maintenance treatment in 3 retrospective studies (n = 34). The OS for patients with Ph+ ALL using dasatinib as maintenance regimen after allo-HSCT at 1.4 to 3 years was 87% to 100% and disease-free survival at 1.4 to 3 years was 89% to 100%. Ninety-three percent of patients with minimal residual disease (MRD) positive status after allo-HSCT became MRD negative. Three prospective studies used nilotinib. In 2 studies where investigators studied patients with advanced chronic myeloid leukemia and Ph+ ALL, the cumulative OS and event-free survival at 7.5 months to 2 years were 69% to 84% and 56% to 84%, respectively. In the third study (n = 5) in patients with Ph+ ALL, nilotinib use resulted in OS at 5 years of 60%. Our review showed that use of TKIs (all generations) after allo-HSCT for patients in CR1 improved OS when given as a prophylactic or preemptive regimen. Limited data suggest that second-generation TKIs (ie, dasatinib) have a better OS, especially in patients with MRD-positive status. Imatinib did not improve OS in patients who were >CR1 at the time of allo-HSCT; for this population, no data were available with newer generation TKIs. The evaluation of survival benefit with newer generation TKIs and their efficacy in patients in >CR1 needs further study in large randomized clinical trials.

Multiple Myeloma (MM) is primarily a disease of old age with a median age of sixty-nine years at diagnosis. The development of novel therapies for induction and use of autologous stem cell transplantation has resulted in improved clinical outcomes and better quality of life for MM patients. Elderly patients, comprising the majority of MM population, have a higher incidence of age-related comorbidities, frailty and organ dysfunction which complicates the coordination of treatment and limits the selection of therapies. Even in the era of multiple chemotherapeutic options, the clinical heterogeneity of the myeloma patients’ demands personalized treatments which often require dose-adjustments or dose delays. The use of reduced-dose regimens and various comorbidity indices has improved clinical outcome and regimen tolerability in MM patients with renal, neurological and bone abnormalities. We focus on advancements in the treatment of multiple myeloma with the goal to guide clinicians towards patient-specific management.

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are at a very high risk of hepatitis B virus reactivation (HBVr). Lamivudine is commonly used as prophylaxis against HBVr in high-risk patients undergoing allo-HSCT. Unfortunately, its efficacy is diminishing due to the development of HBV mutant drug-resistant strains. With the availability of newer antiviral agents such as entecavir, telbivudine, adefovir, and tenofovir, it is important to assess their role in HBVr prophylaxis. A comprehensive search of 7 databases was performed to evaluate efficacy of antiviral prophylaxis against HBVr in allo-HSCT patients (PubMed/Medline, Embase, Scopus, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials.gov (June 21, 2017)). We identified 10 studies, with 2067 patients undergoing allo-HSCT; these primarily evaluated the use of lamivudine and entecavir as prophylaxis against HBVr in patients undergoing allo-HSCT because there were little or no data about adefovir, telbivudine, or tenofovir as prophylaxis in this specific patient population. Thus, included studies were categorized into 2 main prophylaxis groups: lamivudine and entecavir. Results of our meta-analysis suggest that entecavir is very effective against HBVr, although further clinical trials are required to test efficacy of new antivirals and explore the emerging threat of drug resistance.

We reviewed emerging immune strategies for multiple myeloma (MM) therapy excluding US FDA approved drugs. In relapsed refractory MM, isatuximab (anti-CD38) monotherapy achieved overall response (OR) of 24%. Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab. We included seven clinical trials on chimeric antigen receptor (CAR) T cells. CAR T-cell targets include BCMA, CD19, KLC and CD138. A recent experience of CAR T-cell (B-cell maturation antigen) therapy in advanced MM has shown global response of 100%. The future of monoclonal antibodies and adoptive T cells for MM treatment seems promising.

INTRODUCTION -The prognosis of acute myeloid leukemia (AML) in elderly population is inherently poor due to multiple factors including: frailty, medical co-morbidities and high treatment related morbidity with traditional induction chemotherapy and presence of adverse risk cytogenetics in 17-20% of patients. For patients who are not candidates for intensive chemotherapy, outcomes in terms of complete response/complete response with incomplete hematologic response (CR/CRi) and median overall survival (mOS) have been evaluated using hypomethylating agents(HMA) including azacytidine (AZA)(CR/CRi=18-27.8%, mOS=10.4-24.5 months) and decitabine (CR/CRi= 18-47%, mOS= 7-7.8 months). Recently, addition of venetoclax to HMA has shown to further improve CR/CRi (75%) and mOS (17.5 m). We conducted a systematic review of literature to identify recent studies that were published between 2015-2020 with an aim is to evaluate newer combination drug regimens (CDR) involving hypomethylating agents (AZA and decitabine) in treating elderly patients with newly diagnosed AML. METHODS- A comprehensive literature search was conducted in PubMed, Embase, and Cochrane databases. We included phase I/II studies that used CDR with HMA in elderly patients with newly diagnosed AML. RESULTS- Initial database search lead to 1120 studies. After exclusion (duplicates, case reports/series, relapsed/refractory AML) final analysis included 12 studies (n=655). Seven phase I/II with CDR using decitabine (n=500) were included in our review. Drugs used in combination included gemcitabine ozagamicin (n=40, CR/CRi =45%, mOS= 7 m), cladribine and low dose cytarabine (n=118, CR/CRi= 68%, mOS =13.8 m), vadastuximab talirine (n=53, CR/CRi=70%, mOS=11.3 m) and selinexor (n=5, CR/Cri= 80%) . In addition, three studies compared outcomes of CDR involving decitabine with all trans retinoic acid (ATRA)(n=93, ORR=21.9% vs 13.5%, p=0.06; mOS= 8.2 m vs 5.1 m, p=0.006) or talacotuzumab (CR/CRi= 15% vs 11%, p=0.44; mOS= 5.36 m vs 7.26 m, p=0.78) or bortezomib (CR/CRi= 39% vs 38%, p=0.91, mOS=9.3 m vs 8.9,p=0.18) to decitabine alone. In addition, cladribine and low dose cytarabine with decitabine in patients with adverse cytogenetics showed a decent CR/CRi of 50%, mOS= 10.5 months. In TP 53 positive mutations, CR/CRi was 40% and mOS was 5.4 months. Five phase I/II studies using CDR with AZA (n=155) were included in our review. Drugs included midostaurin (n= 88 , CR/CRi=25-29% mOS= 6-8 m) and pracinostat (n= 50, CR/CRi =46% mOS=19.1 m), In addition, two studies compared outcomes using CDR involving AZA with panobinostat (n=22, CR= 22.4 vs 30.8%, OS at 1 year = 60% vs 70%) or entinostat (n=18, ORR= 0% vs 16.6%, mOS=6 m vs 13 m) to AZA alone. None of the two comparative CDR studies using AZA showed superior outcome compared to AZA alone. CONCLUSIONS - Novel drug combinations involving decitabine including cladribine and low dose cytarabine, vadastuximab talarine showed superior CR/CRi and mOS compared to decitabine alone used in historic studies. In addition, CR/CRi were similar to HMA and venetoclax combination. In small number of patients, CDR with selinexor also showed superior CR/CRi compared to decitabine alone. CDR involving decitabine and ATRA showed superior mOS in direct comparison with decitabine alone. In addition, cladribine, low dose cytarabine and decitabine has shown promising outcomes in patients with adverse cytogenetics. Among CDR involving AZA only Proctinostat showed superior CR/CRi and mOS compared to historic studies with AZA alone. A recent phase III study though involving this CDR in comparison with decitabine was terminated early due to lack of efficacy on preliminary analysis. The above listed efficacious CDR involving decitabine in phase I/II studies need to be evaluated in large, randomized trials to assess for definitive benefit. If proven efficacious in larger studies, they could serve as additional first line CDR options in addition to HMA and venetoclax in treating elderly patients with newly diagnosed AML. Disclosures No relevant conflicts of interest to declare.

We present an unusual case of hyponatremia in an ambulatory hypothyroid patient and review related published literature on PubMed including, original articles, reviews and case reports that describe or refute the association and mechanism for the development of hyponatremia in hypothyroidism. A 50-year-old female presented in ambulatory clinic with complaints of bilateral hand swelling, fatigue, dizziness, and unsteadiness while walking. Laboratory investigations revealed that she had hypothyroidism and hyponatremia. Thyroid hormone replacement therapy resulted in resolution of hypothyroidism symptoms as well as hyponatremia. A comprehensive search of related literature regarding the development of chronic hyponatremia in hypothyroidism revealed two schools of thought, which we have summarized in this report. Based on our observations, we conclude that due to overlap in symptoms of hyponatremia and neurological manifestations of hypothyroidism, it is imperative to screen hypothyroid patients for underlying hyponatremia and treat accordingly in order to prevent long-term complications of chronic hyponatremia. Hyponatremia secondary to hypothyroidism resolves with appropriate thyroid hormone replacement therapy, which shows convincing evidence of an association between the two entities.

Background. Relapsed Ewing’s sarcoma (RES) is an aggressive malignancy with poor survival. Although high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) given after conventional chemotherapy (CC) has shown survival benefits, it is not generally used in the United States for RES. We performed a systemic review to evaluate the benefits of HDCT for RES. Methods. Literature search involved Medline, Embase, and Cochrane database. We included studies with RES patients treated with HDCT/ASCT. Results. Twenty-four studies with total of 345 reported RES patients that got HDCT were included in final analysis. Seventeen studies had patients with multiple malignancies including RES, while seven had only RES patients. At 2 and 3–5 years, event-free survival (EFS) in studies with only RES patients ranged 42–47% and 20–61% and overall survival (OS) ranged 50–66% and 33–77%, respectively. In studies with combined patients that reported outcomes of RES separately, the EFS at 1–3 and 4 years was 36–66% and 17–50%, respectively. The OS at 1-2 and 3-4 years was 40–60% and 50–70%. Conclusions. Most studies using HDCT/ASCT as consolidation regimen showed improved survival benefits compared to CC. Randomized controlled studies are needed to determine true clinical benefits of HDCT followed by ASCT in patients with RES.

e20048Background: Primary plasma cell leukemia (pPCL) is rare but aggressive disease with median overall survival (mOS) of less than one year. Our aim is to review its unique biology, efficacy of a...

7050Background: Relapse after allogeneic hematopoietic stem cell transplantation (AlloHSCT) for Ph+ve acute lymphoblastic leukemia (Ph+ ALL) remains the major cause of treatment failure. Use of tyr...