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• The long-term outcomes of patients living with HIV who undergo allogeneic transplant are somewhat similar to those without HIV. • Prospective trials are urgently needed to evaluate the optimal donor, stem cell source, conditioning regimen, and graft-versus-host disease prophylaxis. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for hematologic malignancies in persons living with HIV (PLHIV), however, uncertainties exist in many domains related to their care, including optimal donor selection, conditioning regimen, immunosuppression for graft-versus-host disease (GVHD), and long-term outcomes. We undertook a comprehensive systematic review from multiple databases to evaluate the foregoing uncertainties. The final sample comprised 49 patients (median age at HCT, 34 years; 46 males [93.8%]). Acute GVHD (aGVHD) was reported in 19 patients (59.3%) in the overall cohort, with grade II in 12 (37.5%) and grade III in 2 (6.2%). In the entire cohort, overall survival (OS) was 81.6% at 6 months and 56.6% at 12 months. Among 32 patients, the OS at 6 months was 73.3% for patients who received myeloablative conditioning (MAC) and 88.2% for those who received reduced-intensity conditioning (RIC), and OS at 12 months was 53.3% for MAC and 58.8% for RIC. Twenty-four patients were alive in complete remission on long-term follow-up, with 25 deaths reported. Fifteen deaths (60%) occurred due to relapse, including 3 (12%) from infection, 2 (8%) from GVHD, and 5 (20%) from other causes, including renal failure, respiratory failure, and liver failure. To our knowledge, this is the largest series of allo-HCT in PLHIV reported to date, and our results indicate that clinical outcomes (including engraftment, infection rate, and survival) are not significantly different from those in patients without HIV (historical controls). RIC regimens are associated with a slightly greater likelihood of survival compared with MAC regimens. Prospective trials are critically needed to evaluate the optimal conditioning regimens, ideal donor source, and most appropriate GVHD prophylaxis. [ABSTRACT FROM AUTHOR]

Since Human leukocyte antigen (HLA) and ABO blood group system are inherited independently and with up to 50% of allogeneic hematopoietic cell transplantations (HCT) are performed with donor-recipient ABO incompatibility, recipients are at increased risk for acute and delayed hemolytic reaction and delayed RBC precursors engraftment; i.e. pure RBC aplasia (PRCA). PRCA is a sever consequence of major and bi-directional ABO mismatch after alloHCT, leading to frequent transfusions, iron overload and secondary complications. Risk factors for PRCA after Major ABO incompatibility include; stem cell source, conditioning intensity, and titer of iso-agglutinins. Treatment is mostly supportive with transfusions and growth factors as well as withdrawing immunosuppressive therapy (IS). Targeting recipient immune system with high-dose steroids, DLI, and rituximab have been reported with variable results. Here we report a case series of a novel method of targeting recipient iso-agglutinins-producing B cells by Ibrutinib. We report 3 cases of PRCA refractory to conventional therapy who responded to ibrutinib, a BTK inhibitor targeting recipient B cells to allow engraftment of donor RBCs. Patient, transplant and disease characteristic including prior therapies, time to transfusion independence, and switch of blood group (BG) are summarized in Table 1. First patient's day 30 post-transplant bone marrow biopsy (BMBx) showed complete remission (CR) with full donor chimera, but BG remained O. He developed severe anemia requiring transfusions and Day 100 BMBx showed CR with markedly decreased number of erythroid progenitors. He did not respond to IS withdrawal, prednisone, rituximab or bortezomib. But BMBx 4 weeks after starting ibrutinib showed trilineage hematopoiesis. Second patient remained RBC transfusion dependent post-HCT with Day 100 biopsy showing PRCA and full donor chimera. BG remained O. He developed severe GVHD of skin and eyes after DLI and His PRCA was refractory to multiple lines of therapies but responded to ibrutinib. Third patient underwent HCT for refractory AML with MDS; Anti-A isoagglutinin level pre-HCT was high and patient underwent plasma exchange. Day 30 BMBx showed CR and full donor chimera. Day +73 BMBx showed CR with near absent erythropoiesis. PRCA was refractory to rituximab and responded to ibrutinib. All three patients with PRCA refractory to multiple lines of therapy responded to ibrutinib with median time to transfusion independence of 4 weeks and median time to BG switch of 6 weeks. All patients tolerated therapy well. Our experience at City of Hope shows that ibrutinib could offer a safe and efficacious treatment option for cases of refractory PRCA. Prospective studies are needed to assess if early therapy with ibrutinib could reduce the morbidity resulting from frequent transfusions, and GVHD complications. [ABSTRACT FROM AUTHOR]

Blinatumomab (Blina) and inotuzumab ozogamicin (Ino) have shown remarkable responses in relapsed/refractory (RR) B-cell acute lymphoblastic leukemia (ALL), however, a significant number of patients (pts) relapse. Prior reports suggest that allogeneic hematopoietic stem cell transplantation (SCT) consolidation after Blina/Ino may be associated with increased transplant related complications. To address this issue, we assembled a large retrospective multi-center cohort of RR ALL pts who received SCT after Blina/Ino. Medical records of RR ALL pts who received SCT after Blina or Ino at 11 academic transplant centers across USA were reviewed. These pts were evaluated for response and toxicity after SCT. From December 2014 to May 2019, 223 and 86 pts who received Blina and Ino, respectively, for RR ALL outside clinical trials were identified. Among them 85 (38%) pts in the Blina group (gp) and 21 (25%) pts in the Ino gp who achieved remission and underwent SCT were included in this analysis. Median age of pts in the Blina and Ino gp was 59 (range [R], 18-72) and 43 (R, 20-75) years, respectively. Median number (no.) of therapies (Rx) prior to SCT in Blina and Ino gp was 2, ranging from 2-5 and 2-6, respectively. Five (6%) and 2 (5%) pts in the Blina and Ino gp, respectively, received second SCT. Median time from remission to SCT in Blina gp was 1.7 months (mo) (R, 0.20 to 13.2) and in Ino gp was 4.3 mo (R, 1-13.3). In the Blina and Ino gp: 36.5% vs. 38%, 42% vs. 42%, 15% vs. 9.5% and 6% vs. 9.5% had matched related donor (MRD), matched unrelated donor (MUD), haploidentical and cord blood SCT, respectively. Acute graft versus host disease (aGVHD), chronic (c) GVHD, veno-occlusive disease (VOD) and infectious complications post SCT were observed in 28 (33%), 14 (16.5%), 2 (2%) and 12 (14%) pts, respectively, in the Blina gp. While in the Ino gp, 8 (38%), 1 (5%), 3 (14%) and 4 (19%) pts had these complications, respectively. Six (7%) and 2 (9%) pts had TRM within 100 days of SCT in Blina and Ino gp, respectively. The median PFS and OS in Blina gp was not reached (NR); 66% were progression free and 62% were alive at 2 yrs (Fig 1 A & B). Similarly, median PFS and OS in the Ino gp was NR; 53% were progression free at 6 mo and 53% were alive at 1 yr mark (Fig 1 C & D). In the Blina gp, history of CRS (p= 0.41), no. of prior Rx (p= 0.5), time from response to SCT (p=0.48), and type of donor (p= 0.7) were not significantly associated with GVHD. Similarly, in the Ino gp, no. of prior Rx (p= 0.6), time from response to SCT (p=0.84), type of donor (p= 0.9) were not significantly associated with GVHD. Occurrence of VOD in the Ino gp was not significantly associated with type of donor (p= 0.3), second SCT (p= 0.1), no. of prior Rx (p= 0.6), myeloablative conditioning (p> 0.9) or time from response to SCT (p= 0.5). Our real-world analysis suggests that SCT is feasible and effective after Blina or Ino in pts with RR ALL. [ABSTRACT FROM AUTHOR]

Despite of the continuous increase in the number of volunteer donors available through the registry, many patients who require an allogeneic hematopoietic cell transplantation (HCT) cannot find a fully-matched donor. While a mismatched unrelated donor (MMUD) is frequently available, it is associated with inferior outcomes and increased risk of graft-versus-host disease (GvHD). Post-transplant cyclophosphamide (PTCy) has been effective in haploidentical HCT, and increasingly used in matched donor HCTs. However, limited data exist in MMUD setting. We conducted a prospective single center trial (NCT 03128359) of PTCy for MMUD HCT with the primary objective of estimating 1-year GvHD-free relapse/progression-free survival (GRFS). As of October 2019, all planned 39 patients have been enrolled with a median follow up of 11 months (range: 1-23). Here we present the preliminary estimate of 1-year GRFS and other HCT outcomes in two strata; myeloablative conditioning (n=19) using Fludarabine (90 mg/m2) and FTBI (1200 cGy) or reduced intensity conditioning (n=19) using Fludarabine (100 mg/m2) and Melphalan (140 mg/m2 or 100 mg/m2 if >60 years old). Patients between 0 to 75 years of age and KPS of ≥70% with hematologic malignancies undergoing HCT from a 7/8 HLA-matched (A-, B-, C-, and DR-) donor were eligible. Patients with donor specific antibodies to the mismatched HLA-locus were excluded. All patient received PBMCs (3-5 × 106/kg) followed by GVHD prophylaxis consisting of PTCy (50 mg/kg for 2 days), Tacrolimus (1 mg), and mycophenolate mofetil (1 gr 3 × a day). Median age at the time of HCT was 53 years (range: 21-72), and 50% of patients were male. Disease risk was low in 47% (n=18), intermediate in 37% (n=14), and high in 16% of the patients (n=6). At transplant, 29 patients were in complete remission, and 9 had active disease. HCT-CI was 0 in six (16%) and 1-2 in 15 (39%) and >2 in 17 (45%) patients. Donors' median age was 32 years (range: 19-53) and donors were mismatched at HLA-A (n=14), -B (n=12), -C (n=8), or DR-loci (n=5). Median number of mismatches was 2 of 12 (range: 1-4). Female to male donor HCT was in 11% of recipients. Neutrophil engraftment occurred in all patients (median time to engraft: 16 days; range 13-35). One-year overall survival (OS) and GRFS were 92% (95% CI: 70-98) and 70% (95% CI: 51-83), respectively. Non-relapse mortality and relapse rate at 1 year were at 8% (95% CI: 2-29) and 13% (95% CI: 5-34), respectively. Cumulative incidence of day 100 acute GvHD grade 2-4 was 50% (95% CI: 35-71) and 1-year chronic GvHD was 56% (95% CI: 39-81). No severe chronic GvHD by the NIH criteria was observed. In conclusion, the data from our phase II trial of PTCy showed highly promising OS/GRFS in patients receiving 7/8 MMUD HCT, and that PTCy in MMUD setting offers an alternative and effective HCT approach for patients who do not have an available matched donor. [ABSTRACT FROM AUTHOR]