Incidence and risk factors for secondary graft failure in uniformly treated patients with severe aplastic anemia receiving fludarabine and cyclophosphamide for conditioning and matched sibling bone marrow graft as stem cell source.

BACKGROUND AIMS: Graft failure after allogeneic transplant for aplastic anemia is problematic. The risk of graft failure depends on multiple variables, including the preparative regimen, donor type, stem cell dose and source among other variables. METHODS: We performed a retrospective analysis of patients with aplastic anemia who underwent matched-sibling allogeneic transplant at a single center. RESULTS: We identified 82 patients who fit the inclusion criteria. One had primary graft failure and was excluded from this analysis. The recipient median age was 22 years. The donor median age was 23 years. The median time from diagnosis to transplant was 1.6 months. The median number of red cell transfusions before transplant was nine. The median number of platelet transfusions before transplant was 18. Thirteen patients developed secondary graft failure, with a cumulative incidence at 5 years of 16% and median time to develop secondary graft failure of 129 days. All patients engrafted with a median time for neutrophil engraftment of 19 days and a median time for platelet engraftment of 22 days. The survival of patients with or without secondary graft failure was not different. Major or bidirectional ABO incompatibility and older recipient age were statistically significantly associated with greater risk of secondary graft failure. CONCLUSIONS: Secondary graft failure is a significant complication after allogeneic transplant for SAA. Identification of recipients at risk and mitigating the potential risks of this complication is warranted.

A comprehensive review of the role of bone marrow biopsy and PET-CT in the evaluation of bone marrow involvement in adults newly diagnosed with DLBCL.

Diffuse large B cell lymphoma (DLBCL) is one of the most prevalent subtypes of non-Hodgkin lymphoma (NHL) and is known for commonly infiltrating extra-nodal sites. The involvement of the bone marrow by lymphoma cells significantly impacts the staging, treatment, and prognosis among the extra-nodal sites in DLBCL. Bone marrow biopsy has been considered the standard diagnostic procedure for detecting bone marrow involvement. However, advancements in imaging techniques, such as positron emission tomography-computed tomography (PET-CT), have shown an improved ability to detect bone marrow involvement, making the need for bone marrow biopsy debatable. This review aims to emphasize the importance of bone marrow evaluation in adult patients newly diagnosed with DLBCL and suggest an optimal diagnostic approach to identify bone marrow involvement in these patients.

Myeloablative Haploidentical Donor Hematopoietic Transplantation Using Post-Transplantation Cyclophosphamide and Antithymocyte Globulin.

Haploidentical donor (haplo-) hematopoietic stem cell transplantation (HSCT) with post-transplantation cyclophosphamide (PTCy) is now performed on a large scale worldwide. Our patient outcomes did not completely reflect the results published by other groups. We herein present the results of 60 patients with hematologic malignancies treated homogeneously on a modified version of the standard protocol by adding ATG as an additional graft-versus-host disease (GVHD) prophylaxis measure. This was a retrospective analysis of 60 haplo-HSCT recipients using a myeloablative conditioning regimen with antithymocyte globulin and PTCy for GVHD prophylaxis. At 5 years, overall survival was 59.2%, relapse-free survival (RFS) was 48.6%, and chronic GVHD (cGVHD) and relapse-free survival was 40%. The median time to neutrophil and platelet engraftment was 16 days and 28.5 days, respectively. The rates of grade II-IV acute GVHD and extensive cGVHD were 46.7% and 23.3%, respectively. The cumulative incidence of relapse was 30%, nonrelapse mortality was 21.6%, and transplantation-related mortality was 11%. Higher Disease Risk Index and 50% HLA match were associated with lower RFS. Female donor to male recipient and older donor age were associated with an elevated risk of cGVHD. The use of PTCy might not yield the same results in different populations. Many remaining questions need to be addressed in randomized trials, including optimal graft source and donor, date of calcineurin inhibitor initiation, personalized or targeted dose of PTCy, immune reconstitution, and others.

Successful restoration of checkpoint inhibitors efficacy after allogeneic hematopoietic cell transplant for classic Hodgkin lymphoma patients.

BACKGROUND: Classic Hodgkin lymphoma (cHL) is a highly-curable disease. However, relapses after bone marrow transplant are challenging especially relapses after allogeneic transplant. METHODS: A retrospective chart review of the institution transplant database to summarize the safety and efficacy of checkpoint inhibitors (CPIs) use for cHL relapses postallo-HCT in patients who already failed to derive sustained benefit from CPIs received prior to allo-HCT. RESULTS: Six cases were identified and reviewed. All patients received and failed to derive sustained benefit from CPIs and brentuximab vedotin preallo-HCT. The median age at the time of allo-HCT was 28.6 years (IQR 23.6-34.2), the median number of lines received prior to allo-HCT was 6.5 (range 5-9). The median duration of CPI therapy prior to allo-HCT was 8.1 months (IQR 6.7-12.9). The median time between the discontinuation of CPI and allo-HCT was 5.78 months (IQR 3.15-15.8). The median time to progression postallo-HCT was 5.75 months (IQR 2.6-11.7). The median time between allo-HCT and re-challenge with a CPI was 7.6 months (IQR 3.2-28.6). The median time of follow up after starting postallo-HCT CPIs was 16 months (IQR 7.25-25.75). Five out six patients responded and two patients developed GvHD. CONCLUSION: Our report shows preserved efficacy without any new safety signals by using CPIs postallo-HCT despite using and having failed to derive sustained benefit from CPIs preallo-HCT.

Improved survival of adolescents and young adults patients with T-cell acute lymphoblastic leukemia.

Aim: The outcome of T-cell acute lymphoblastic leukemia (T-ALL) has improved with the use of pediatric-inspired protocols in the adolescents and young adults (AYA) population. There is limited literature regarding the outcome of T-ALL/lymphoblastic lymphoma (LBL) AYA patients treated with pediatric protocols. Methods: A total of 35 T-ALL/LBL-AYA patients ages between 14 and 55 years were treated with AYA-15 protocol. Results: At a median follow-up of 5 years the overall survival, disease-free survival and event-free survival are 71%, 62% and 49.6% respectively. Toxicities were within the expected range. Conclusion: Our single-center experience real-world data in treating T-ALL/LBL-AYA patients with pediatric-inspired protocol demonstrates encouraging results of high survival rate and excellent tolerability for patients aged 18-55 years.

"Incidence and significance of donor-specific antibodies in haploidentical stem cell transplantation".

PGF is a devastating complication after allogeneic transplant. We retrospectively analyzed our haploidentical transplant registry to report the incidence and impact of DSA and anti-HLA on engraftment. 107 patients were identified. Median recipient-age of 22, median donor-age of 31. Sixty-two patients had AML (58%), 29 had ALL (27%), 16 (15%) had other malignancies. Sixty-one recipients (57%) had positive anti-HLA, 56 of them had the DSA results available, of these 17 patients had DSAs (15% of the total number of patients, or 28% of patients who have anti-HLA antibodies). The median cumulative MFI was 2062. Sixty-three percent of the DSA were against class-II HLA antigens. The OS, CIR, aGvHD, and cGvHD did not differ between patients with and without anti-HLA antibodies, nor between patients with and without DSA. The gender of the recipient and donor, as well as the gender mismatch between recipient and donor, were statistically associated with the incidence of anti-HLA antibodies. Three patients only developed GF (2.8%), one was primary (0.9%) and the other two secondary GF (1.9%). None of the GF cases was in patients with anti-HLA antibodies or DSA. The presence of anti-HLA or DSAs did not affect the outcomes including the incidence of PGF.

Infectious Complications and Preventative Strategies following Chimeric Antigen Receptor T-cells (CAR-T cells) Therapy for B-Cell Malignancies.

Several chimeric antigen receptor T-cell constructs (CAR-T cells) are currently approved for the treatment of B-cell malignancies, including non-Hodgkin lymphoma and acute lymphoblastic leukemia. Additionally, multiple other products are being investigated and developed for other hematological malignancies and solid cancers. Patients receiving CAR-T cells are at increased risk of infectious complications that lead to increased morbidity and inferior mortality in these patients. In this review, we discuss the literature on the incidence and types of infection in patients in the early and late-phase after CAR-T cells infusion. Additionally, we summarize the current literature on prophylaxis against viral, bacterial, and fungal infections after CAR-T cells infusion and the utility of preventative and supportive measures including intravenous immunoglobulins and myeloid growth factors.

Allogeneic transplant compared to pediatric-inspired therapy for Philadelphia chromosome-negative adolescent and adult ALL in first complete remission.

BACKGROUND: Pediatric-inspired non-transplant regimens for adolescent and adult ALL patients are becoming standard in many institutions. We aimed to compare a cohort of patients receiving a pediatric-inspired protocol to a cohort of patients treated with adult type ALL therapy followed by allografting after achieving CR1. METHOD: Eighty-five adolescent and adult ALL patients treated with CALGB 19802 protocol who received MSD transplant in CR1 were retrospectively compared to a matched cohort of 72 adolescent and adult ALL patients treated with a modified version of Children's Cancer Group (CCG) 1900 protocol. RESULTS: The five years OS in the allo-HCT cohort was 63.1% compared to 80.2% in the pediatric-inspired chemotherapy arm (P = 0.03). The five years EFS in the allo-HCT arm was 58.8% compared to 61.6% in the pediatric-inspired chemotherapy arm (P = 0.07). The five years DFS in the allo-HCT arm was 58.8% as compared to 71.9% in the pediatric-inspired chemotherapy arm (P = 0.07). The relapse rate in the allo-HCT cohort was 30.58% compared to 21.68% in the pediatric-inspired chemotherapy arm (P = 0.16). The NRM in the allo-HCT cohort was 10.59 as compared to 6.45 in the pediatric-inspired chemotherapy arm (P = 0.3). CONCLUSION: For adolescent and adult patients with Ph-negative ALL, pediatric-inspired chemotherapy resulted in higher OS compared to allo-HCT.