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ABSTRACT Background Methods Results Conclusion The optimal TBI dose for ALL patients undergoing allogeneic SCT is still not clearly defined.Single‐center retrospective analysis of high‐risk ALL patients in CR1 treated with 8 Gy (n = 22) or 12 Gy (n = 50) TBI in combination with fludarabine and PTCy. Median patient age in the 8 Gy TBI cohort was 63 (37–79) and 37 (18–56) in the 12 Gy TBI cohort and median follow‐up time was 21 months (range 1–92).OS and LFS at 2 years after 8 Gy were 65% and 55% versus 74% and 74% after 12 Gy (p = 0.3 and p = 0.2, respectively). CIR and NRM at 2 years were 27% and 14% after 8 Gy versus 4% and 20% after 12 Gy (p = 0.004 and p = 0.4, respectively). MRD‐positive (+) patients (n = 26) receiving 12 Gy (n = 19) showed better OS (p = 0.01), LFS (p = 0.009), GRFS, lower CIR (p = 0.02), and similar NRM than did MRD+ patients receiving 8 Gy (n = 7). MRD‐negative (−) patients (n = 38) receiving 12 Gy (n = 27) had similar OS, LFS, GRFS, lower CIR, and higher NRM (p = 0.04) than did MRD− patients receiving 8 Gy (n = 11).Our study demonstrates that 8 Gy TBI in comparison to 12 Gy TBI results in low NRM but a high relapse rate with similar OS, LFS, and GRFS. In MRD+ high‐risk ALL patients, allogeneic SCT with 12 Gy TBI leads to improved OS, LFS, GRFS, and a low relapse rate. Prospective studies comparing the different treatment regimens with larger MRD patient cohorts are needed to confirm this data. [ABSTRACT FROM AUTHOR]

Objective: Allogeneic stem cell transplantation (allo‐SCT) may have a curative potential due to the graft versus lymphoma effect. In this study, we aimed to compare transplant outcomes between refractory‐T‐NHL (ref‐NHL) and Chemosensitive‐T‐NHL (CS‐T‐NHL). Materials and Methods: We retrospectively reviewed the records of 26 ref‐NHL and 29 CS‐T‐NHL consecutive patients who underwent allo‐SCT at our center and compared the transplant outcomes between the groups. Results: All patients were heavily pretreated with 27% of patients relapsing post‐auto‐SCT and two patients in the ref‐T‐NHL post‐allo‐SCT. Patients were transplanted mainly from unrelated donors. There were no differences in leucocytes and platelet engraftment between the two groups. At 3 years, the relapse incidence was 34% in Ref‐TNHL and 19% in CS‐TNHL (p =.33), with non‐relapse mortality rates of 28% and 22%, respectively (p =.52). Female patients and those with a previous auto‐SCT had lower relapse incidence (p =.045, p =.003). The 3‐year overall survival was 39% in Ref‐TNHL and 56% in CS‐TNHL (p =.15). Trends for improved progression‐free survival (PFS) and graft‐versus‐host disease relapse‐free survival (GRFS) were observed in the CS‐TNHL group (PFS: 60% vs. 30%, p =.075; GRFS: 38% vs. 21%, p =.1). Conclusion: Acknowledging the retrospective nature of our study, our results indicate that allo‐SCT has a curative potential in patients with T‐NHL even in refractory status. [ABSTRACT FROM AUTHOR]

Pre‐transplant minimal residual disease (MRD) impacts negatively on post‐transplant relapse risk in acute myeloid leukemia (AML). Therapeutic drug monitoring by calculating area under the curve (AUC) was developed to optimize busulfan (Bu) exposure. Here, we compared post‐transplant outcomes after individualized versus fixed busulfan dosage in intermediate‐risk AML who achieved CR prior to allograft focusing on pre‐transplant flow‐MRD. Eighty‐seven patients (median, 56 years) with intermediate‐risk AML and pre‐transplant flow‐MRD ("different from normal") were included. Thirty‐two patients received individualized busulfan; 54 fixed dosages. Individualized dosage was adjusted in 25/32 patients: increased, n = 18/25 (72%); decreased: n = 7/25 (28%). After median follow‐up of 27 months, we observed lower 3‐year relapses (6%, 2%–19% vs. 35%, 23%–49% p = 0.02), improved 3‐year leukemia‐free survival (LFS) (78%, 54%–91% vs. 55%, 40%–70% p = 0.009) and − overall survival (OS) (82%, 60%–93% vs. 69%, 54%–81% p = 0.05) after individualized compared to fixed Bu. Non‐relapsed mortality (NRM) and acute graft versus host disease (GvHD) were not different. In multivariate analysis, fixed Bu showed unfavorable impact on OS (hazard ratio [HR] 4.6, p = 0.044), LFS (HR 3.6, p = 0.018) and relapses (HR 3.6, p = 0.033). Fixed Bu also had unfavorable impact on LFS (3.6, 1.1–12.6, p = 0.041) in pre‐transplant MRD‐positive patients. Individualized, AUC‐based, busulfan is associated with lower relapses in intermediate‐risk AML patients allografted in CR and may overcome pre‐transplant MRD‐positivity. [ABSTRACT FROM AUTHOR]

This letter describes the experience of the American University of Beirut Medical Center in Lebanon with haploidentical stem cell transplant (haplo-SCT) for hematological malignancies in adult patients. Haplo-SCT made it possible through universal and rapid donor availability for most of the adult patients with leukemia or lymphoma not only in the Middle East but also globally. Moreover, the use of post-transplant cyclophosphamide (PTCy) and reduced intensity conditioning (RIC) regimens when indicated improved the outcome and decreased the toxicity of haploidentical stem cell transplant.RIC regimens also allowed its use in the elderly population. Patients from throughout the Middle East come to our center, the American university of Beirut Medical Center, to receive this transformative type of stem cell transplant. In this paper, we discuss the results of haplo-SCT with PTCy done on adult patients with hematological malignancies in our center from 2015 to 2021. The results are encouraging and show that haplo-SCT should be considered more often in the Middle Eastern countries. The subgroup analysis showed the importance of achieving complete remission of the disease prior to transplant to improve outcomes in our center. There is a paucity of literature on the outcomes of haplo-SCT in the Middle East which may contribute to the limited number of centers that offer this type of SCT. Herein, we aim to fill this gap in the hopes of encouraging the implementation of this potentially curative modality of treatment to a larger extent in the Middle East., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors JE-C and RM declared that they were editorial board members of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 El Cheikh, Bidaoui, Sharrouf, Zahreddine, Massoud, Nehme, Kreidieh, Moukalled, Abou Dalle, Mahfouz and Bazarbachi.)

Vaccines against SARS-CoV-2 have shown remarkable efficacy and thus constitute an important preventive option against coronavirus disease 2019 (COVID-19), especially in fragile patients. We aimed to systematically analyze the outcomes of patients with hematological malignancies who received vaccination and to identify specific groups with differences in outcomes. The primary end point was antibody response after full vaccination (2 doses of mRNA or one dose of vectorbased vaccines). We identified 49 studies comprising 11,086 individuals. Overall risk of bias was low. The pooled response for hematological malignancies was 64% (95% confidence interval [CI]: 59-69; I²=93%) versus 96% (95% CI: 92-97; I²=44%) for solid cancer and 98% (95% CI: 96-99; I²=55%) for healthy controls (P<0.001). Outcome was different across hematological malignancies (P<0.001). The pooled response was 50% (95% CI: 43-57; I²=84%) for chronic lymphocytic leukemia, 76% (95% CI: 67-83; I²=92%) for multiple myeloma, 83% (95% CI: 69-91; I²=85%) for myeloproliferative neoplasms, 91% (95% CI: 82-96; I²=12%) for Hodgkin lymphoma, and 58% (95% CI: 44-70; I²=84%) for aggressive and 61% (95% CI: 48-72; I²=85%) for indolent non-Hodgkin lymphoma. The pooled response for allogeneic and autologous hematopoietic cell transplantation was 82% and 83%, respectively. Being in remission and prior COVID-19 showed significantly higher responses. Low pooled response was identified for active treatment (35%), anti-CD20 therapy ≤1 year (15%), Bruton kinase inhibition (23%), venetoclax (26%), ruxolitinib (42%), and chimeric antigen receptor T-cell therapy (42%). Studies on timing, value of boosters, and long-term efficacy are needed. This study is registered with PROSPERO (clinicaltrials gov. Identifier: CRD42021279051).

Anti-T-cell lymphocyte globulin (ATLG) and posttransplant cyclophosphamide (PTCy) are now widely used strategies to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. Data comparing immune reconstitution (IR) between ATLG and PTCy is scarce. This retrospective study conducted at the University Medical Center Hamburg-Eppendorf (UKE) compares PTCy (n=123) and ATLG (n=476) after myeloablative allogeneic peripheral blood stem cell transplant. Detailed phenotypes of T, B natural killer (NK), natural killer T (NKT) cells were analyzed by multicolor flow at day 30, 100 and 180 posttransplant. Incidence of infections, viral reactivations, GVHD and relapse were collected. Neutrophil engraftment was significantly delayed in the PTCy group (median day 12 vs. day 10, P<0.001) with a high incidence of infection before day+100 in the PTCy arm but a higher Epstein-Barr virus reactivation in the ATLG arm and comparable cytomegalovirus reactivation. Overall incidence of acute GVHD was similar but moderate/severe chronic GVHD was seen more often after PTCy (44% vs. 38%, P=0.005). ATLG resulted in a faster reconstitution of CD8+ T, NK, NKT and gdT cells while CD4 T cells and B cells reconstituted faster after PTCy. Similar reconstitution was observed for T-regulatory cells and B cells. Non-relapse mortality relapse incidence, disease-free survival, and overall survival did not differ significantly between both arms. Even though differences in IR were related to a decreased incidence of infection and moderate/severe cGVHD in the ATLG group they had no impact on any of the other long-term outcomes. However, it remains undetermined which regimen is better as GVHD prophylaxis.

Retinoic acid (RA) was proposed to increase survival of chemotherapy- treated patients with nucleophosmin-1 (NPM-1c)-mutated acute myeloid leukemia. We reported that, ex vivo, RA triggers NPM-1c degradation, P53 activation and growth arrest. PML organizes domains that control senescence or proteolysis. Here, we demonstrate that PML is required to initiate RA-driven NPM-1c degradation, P53 activation and cell death. Mechanistically, RA enhances PML basal expression through inhibition of activated Pin1, prior to NPM-1c degradation. Such PML induction drives P53 activation, favoring blast response to chemotherapy or arsenic in vivo. This RA/PML/P53 cascade could mechanistically explain RA-facilitated chemotherapy response in patients with NPM-1c mutated acute myeloid leukemia.