MON-PP080: Weight Loss Following Allogeneic Stem Cell Transplant Peaks at Four Months and is not Regained after One Year

Abstract Background: Although current antiretroviral therapies have effectively changed the course of HIV-1 infection, it remains an incurable illness. The C-C chemokine receptor type 5 (CCR5) is the key co-receptor for HIV entry into CD4+ T cells. Homozygous 32 deletion (delta32) in CCR5 genes leads to resistance to HIV-1 infection 1. Allogeneic stem cell transplant from a donor with CCR5 delta32/32 mutation was curative for HIV in an HIV-1-infected man (Berlin Patient) with AML 2. It has been challenging to replicate this experience. We present our experience with a single case of successful engraftment of CD34-selected, related haploidentical peripheral blood and CCR5delta32 cord blood stem cell transplant (haplo-cord) in an HIV-1-infected woman who, like the Berlin patient, developed AML and is now doing well at almost one-year post transplantation. Clinical case: A 60-year-old African-American woman was diagnosed with HIV-1- infection in June 2013 and was started on an antiretroviral treatment (ART) regimen consisting of tenofovir, emtricitabine and raltegravir. Her pre-ART viral load and CD4 counts were 1,000,000 copies/ml and 1003 cells/mm3, respectively. In Nov, 2013 she had viral load < 20 copies/ml with CD4 counts of 980 cells/mm3 and her HIV-1 infection was relatively asymptomatic. In March 2017, she was diagnosed with AML with monosomy 7. Her HIV therapy after the AML diagnosis was changed to abacavir- lamivudine -dolutegravir- combination. She achieved morphologic and cytogenetic remission after 1 cycle of standard idarubicin/cytarabine induction chemotherapy. In addition, she received 1 cycle of HiDAC consolidation and was referred for allogeneic stem cell transplant. We identified a CCR5 delta32/32 mutated cord blood unit (CBU) which was 5/8 HLA matched and contained 1.3 x 107 nucleated cells/kg and 3.2 x 104 CD34+ cells/kg. She underwent a combined CD34-selected, haploidentical peripheral blood and CCR5delta32 cord blood stem cell transplant (haplo-cord) in August 2017. Her conditioning regimen was with fludarabine/melphalan/and TBI400 and she also received ATG/MMF/tacrolimus for GVHD prophylaxis. Her neutrophils and platelets engrafted on day 10 and 16, respectively and she was discharged on day +16 post-transplant. Her post-discharge hospital course was complicated by CMV reactivation (no organ involvement) 2 months post-transplant with peak viral level of 1374 copies/ml. She did not have evidence for EBV re-activation or graft-vs-host disease. Her plasma HIV viral load remained undetectable post- transplant while remaining on abacavir/lamivudine and dolutegravir-based ART. Her day+180 bone marrow showed continued AML remission and she remains in clinical remission near one year post-transplant. CD3 chimerism showed 82% haploidentical donor and 8% CBU and 10% recipient on day +15 post-transplant (Figure 1). The chimerism composition switched to 96% CBU by day+34, and became and remained 100% CBU since day+55. CD33 chimerism showed 98% haploidentical donor and 2% cord donor on day+15 post-transplant. It was 81% haploidentical donor and 19% cord on day+55 and became 100% cord by day+100. She has continued CD4, CD8, NK and CD19 cell recovery, with normal T cell subsets currently (Figure 2). Her CD4 count dropped to 27 cells/mm3 at one-month post-transplant and currently is at 673cells/mm3. She is currently 11 months post-transplant and is back to her normal daily activities Conclusion: Haplo-cord transplantation with CCR5 delta 32/32 CBU resulted in rapid engraftment and immune replacement with dominance of the CCR5 delta 32/32 CBU graft in an HIV-1-infected woman. Successful suppression of HIV-1-replication to clinically undetectable levels was maintained throughout the transplant period for up to one year. . Correlative viral and immunological studies are ongoing, along with effects on the latent reservoir, which was detectable pre-transplant. It is possible to identify appropriate CCR5 delta 32/32 CBU units for haplo-cord transplantation in HIV-1- infected patients with implications for HIV-1 cure. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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Venetoclax and Decitabine for T/Myeloid Mixed-Phenotype Acute Leukemia Not Otherwise Specified (MPAL NOS)

Case Reports in Hematology ◽

10.1155/2020/8811673 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4

Author(s):

Heather Klocke ◽

Zhao Ming Dong ◽

Craig O’Brien ◽

Nicholas Burwick ◽

Robert E. Richard ◽

...

Keyword(s):

Stem Cell ◽

Acute Leukemia ◽

Stem Cell Transplant ◽

Treatment Guidelines ◽

Cell Transplant ◽

Allogeneic Stem Cell Transplant ◽

Not Otherwise Specified ◽

Mixed Phenotype Acute Leukemia ◽

One Year ◽

Mixed Phenotype

T/myeloid mixed-phenotype acute leukemia not otherwise specified (MPAL NOS) is an uncommon and aggressive leukemia without well-established treatment guidelines, particularly when relapsed. Venetoclax plus a hypomethylating agent offers a promising option in this situation since studies support its use in both acute myeloid and, albeit with fewer data to date, acute T-cell-lymphoblastic leukemias. We report the successful eradication of T/myeloid MPAL NOS relapsed after allogeneic stem cell transplant with venetoclax plus decitabine. A consolidative allogeneic stem cell transplant from a second donor was subsequently performed, and the patient remained without evidence of disease more than one year later. Further investigation is indicated to evaluate venetoclax combined with hypomethylating agents and/or other therapies for the management of T/myeloid MPAL NOS.

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Quality of Life Following Allogeneic Stem Cell Transplant for MF

Blood ◽

10.1182/blood.v128.22.5805.5805 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5805-5805

Author(s):

Jeanne Palmer ◽

Heidi E. Kosiorek ◽

Veena DS Fauble ◽

Holly Geyer ◽

Amylou C. Dueck ◽

...

Keyword(s):

Stem Cell ◽

Research Funding ◽

Bone Pain ◽

Stem Cell Transplant ◽

Symptom Burden ◽

Cell Transplant ◽

Allogeneic Stem Cell Transplant ◽

Night Sweats ◽

One Year

Abstract Background: Myelofibrosis (MF) is a myeloproliferative neoplasm that is characterized by significant scar tissue and fibrosis in the bone marrow, enlarged spleen and/or liver from extramedullary hematopoiesis, and may include significant constitutional symptoms such as bone pain, night sweats, pruritis, and cachexia. The only curative therapy is allogeneic stem cell transplant. Although the symptom burden has been explored in the literature, the impact of hematopoietic stem cell transplant (HCST) on QoL in patients with MF has not been evaluated. We sought to longitudinally describe QoL in patients undergoing HCST for MF. Methods: We prospectively followed patients undergoing HSCT for MF. We assessed symptoms, functioning, and QoL using the FACT-BMT and MPN-SAF total symptom score (TSS) pre-transplant and at day 30, day 100 and one year post-transplant. Scores at the post-transplant time points were compared with baseline scores by paired t-tests. Pearson correlations between FACT-BMT and MPN-SAF TSS questionnaires were also computed. Results: 16 patients were enrolled [median age 64.0 (49-69) years; 13 (81%) male; 13 (81%) Caucasian], two did not have day 30 data as they died prior to then or did not go to transplant. Fourteen patients had day 30 information, 11 had day 100 information, and only 4 had one year information. Of the 14 who had day 30 information, 6 patients died within the first year, two from treatment related mortality and four from relapse. One patient had intermediate-1 risk, the remainder of the patients were intermediate-2 or high risk. All patients had RIC conditioning. Mean MPN-SAF TSS score was 28.1 (SD=14.2) and FACT-BMT total score was 99.8 (SD=17.4) at baseline. FACT-BMT and MPN-SAF TSS at baseline were inversely correlated; lower symptom score was associated with higher QoL (r=-0.62; p=0.01). FACT-BMT at day 30 was lower (mean change: -12.5, SD=16.7; p=0.03). Two MF-specific symptoms showed improvement that reached statistical significance compared to baseline: night sweats mean improvement day 30, 2.5 (SD=3.1; p=0.01) and mean improvement day 100, 1.7 (SD=2.6; p=0.05, Figure 1); headache mean improvement day 100, 1.5 (SD=1.9) p=0.02. In general, scores showed a worsening at day 30, improvement at day 100 and stability at one year. The MPN-SAF TSS worsened at day 30 (6 points) and improved by day 100 (4.5 points). Changes that showed improvement at day 100 include Brief Fatigue Inventory (BFI) with a mean improvement of 1.2 points and concentration (1 point). Of the four surveys that were collected at one year, a modest decline was noted in BFI (1.5 points), inactivity (1.5 points) and cough (3 points). However improvements were noted in night sweats (2.25 points), abdominal discomfort (1 point), insomnia (1.75 points), bone pain (1 point). Discussion: This is the first study to evaluate serially the QoL and symptom burden of patients who underwent a transplant for MF. A decline in QoL in the first 30 days was observed, with modest improvement at day 100. Few surveys have been completed at 1 year to date in this ongoing study. Collection of surveys past one year may be more informative regarding long-term impact of transplant on quality of life. Figure 1 Figure 1. Disclosures Mesa: Gilead: Research Funding; Novartis: Consultancy; Ariad: Consultancy; CTI Biopharma: Research Funding; Galena: Consultancy; Celgene: Research Funding; Promedior: Research Funding; Incyte: Research Funding.

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Safety and Efficacy of Pembrolizumab Prior to Allogeneic Stem Cell Transplant in Patients with Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2020-138786 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 3-4

Author(s):

Nicholas P. Tschernia ◽

Vaibhav Kumar ◽

Dominic T. Moore ◽

Benjamin G. Vincent ◽

Callie C. Coombs ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Clinical Outcomes ◽

Myeloid Leukemia ◽

Research Funding ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Allogeneic Stem Cell Transplant ◽

One Year ◽

Acute Myeloid

Introduction Up-regulation of inhibitory receptors, such as programmed death-1 (PD-1), is an integral component of acute myeloid leukemia (AML) immune evasion, chemotherapy resistance, and disease progression. Early phase clinical trials investigating immune checkpoint inhibitors (ICIs) in patients with AML have demonstrated promising findings. We previously reported that pembrolizumab administration on day 14 after high-dose cytarabine (HiDAC) salvage chemotherapy in patients with relapsed/refractory (R/R) AML was safe, feasible, and associated with encouraging clinical outcomes. PD-1 blockade prior to allogeneic stem cell transplant (alloSCT) has been associated with increased risks of alloSCT-related toxicity in lymphoma. AlloSCT remains the most established treatment paradigm for curative intent in AML patients who achieve a complete response (CR); however, there are limited data on the clinical outcomes and safety of ICI prior to alloSCT in AML. We set out to compare clinical outcomes of AML patients receiving pembrolizumab prior to alloSCT versus a control group of AML patients receiving alloSCT without prior ICI exposure. Methods We assessed clinical outcomes of patients who enrolled on a phase II clinical trial of HiDAC followed by pembrolizumab 200 mg IV on day 14 (NCT02768792) for R/R AML and subsequently underwent an alloSCT. Date of alloSCT was required to be >30 days from last dose of pembrolizumab. We matched each trial participant who underwent an alloSCT in a 1:2 ratio with controls who received alloSCT at our institution since 2016. Patients were matched on age, sex, age-adjusted hematopoietic cell transplantation-comorbidity index (HCT-CI), donor type, and conditioning intensity. The nonparametric Jonckheere-Terpstra test was used to test for a difference in the ordered severity categories of acute graft versus host disease (aGVHD) within 100 days of transplant. The time-to-event estimates for overall survival (OS) and relapse-free survival (RFS, event is either death or relapse) were calculated using the Kaplan-Meier method and compared using a log rank test. Results Nine out of 37 (24.3%) R/R AML patients treated with HiDAC followed by pembrolizumab received an alloSCT. Baseline characteristics of the R/R AML patients who received pembrolizumab versus R/R AML controls who underwent alloSCT are described in Table 1. One patient in each cohort received an alloSCT with evidence of active disease by flow cytometry (>5% blasts) or hematopathology IHC evaluation, whereas all other patients in both arms were in CR/CRi or MLFS at the time of alloSCT. The pattern of aGVHD severity was similar with the exception of 3 control patients (3/18 or 17%) having grade III-IV aGVHD versus 0/9 pembrolizumab patients (p = 0.92). Notably, 7/9 (78%) patients in the pembrolizumab cohort had no evidence of chronic GVHD. There was a nonsignificant increase in relapses (6/9: 67% vs. 6/18: 33%; p = 0.22) and deaths (6/9: 67% vs. 8/18: 44%, p = 0.42) in pembrolizumab versus control patients, respectively. The median follow-up for survivors was 23 months. Median OS was 21 months for pembrolizumab cohort versus 25 months for control patients. One-year OS was 67% (95% CI, 28%-87%) for pembrolizumab patients versus 78% (95% CI, 51%-91%) for control patients, p = 0.34. One-year RFS was 44% (95% CI, 14%-72%) for pembrolizumab patients versus 67% (95% CI, 40%-83%) for control patients, p = 0.14. Conclusion Treatment with ICI represents a promising therapeutic strategy for AML. Among a cohort of patients treated with HiDAC followed by pembrolizumab for R/R AML, alloSCT appeared to be feasible without increased risk of GVHD or early mortality. Although a small number of patients received alloSCT after pembrolizumab, OS appeared comparable to R/R AML controls who did not receive ICI. The increase in relapse rates seen in the pembrolizumab cohort may have been impacted by the higher proportion of patients with measurable residual disease (MRD) prior to alloSCT (78% vs. 39%, respectively). These data warrant further investigation of ICI prior to and after alloSCT in high-risk AML patients. Disclosures Tschernia: AstraZeneca: Research Funding. Vincent:GeneCentric Therapeutics: Consultancy. Coombs:Abbvie: Consultancy, Honoraria; Genentech: Honoraria; AstraZeneca: Honoraria; MEI Pharma: Honoraria; LOXO Oncology: Honoraria; Octapharma: Honoraria; Novartis: Honoraria. DeZern:MEI: Consultancy; Celgene: Consultancy, Honoraria; Abbvie: Consultancy; Astex: Research Funding. Luznik:WindMil Therapeutics: Patents & Royalties: Patent holder; Genentech: Research Funding; AbbVie: Consultancy; Merck: Research Funding, Speakers Bureau. Riches:Biointelect: Consultancy. Gojo:BMS: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Merck: Research Funding; Amphivena: Research Funding; Genentech: Research Funding. Zeidner:AbbVie: Honoraria, Other: Independent Review Committee; Agios: Honoraria; Daiichi Sankyo: Honoraria; Genentech: Honoraria; Pfizer: Honoraria; Takeda: Consultancy, Honoraria, Other: Travel Reimbursement, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; AsystBio Laboratories: Consultancy; AROG: Research Funding; Forty-Seven: Other: Travel Reimbursement, Research Funding; Merck: Research Funding; Sumitomo Dainippon Pharma Oncology, Inc.: Research Funding.

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