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Summary HLA‐haploidentical haematopoietic cell transplantation with post‐transplant cyclophosphamide (PTCy‐haplo) is emerging as an effective alternative due to donor availability and safety. We conducted a nationwide retrospective study comparing the outcomes of PTCy‐haplo with both anti‐thymocyte globulin (ATG)‐free and ATG‐administered matched unrelated donors (MUD) transplantation, using peripheral blood stem cells as the first transplantation for acute myeloid leukaemia (AML). Our study showed a lower and slower haematopoietic recovery and a higher incidence of infection‐related deaths after PTCy‐haplo than after MUD transplantation. In addition, we revealed an increased risk of acute and chronic graft‐versus‐host disease (GVHD) in ATG‐free MUD transplantation in comparison to PTCy‐haplo. For grades III–IV acute GVHD, the hazard ratio (HR) was 2.71 (95% CI, 1.46–5.01), and for extensive chronic GVHD, the HR was 3.11 (95% CI, 2.07–4.68). There was no significant difference regarding overall survival amongst the groups. In addition, GVHD‐free relapse‐free survival (GRFS) was lower in ATG‐free MUD transplantation than in PTCy‐haplo (HR, 1.46; 95% CI, 1.17–1.82). Notably, ATG‐administered MUD transplantation showed no significant difference in GRFS from PTCy‐haplo, negating the advantage of PTCy. Our results suggest that PTCy‐haplo could be viable for AML patients without an HLA‐matched related donor. [ABSTRACT FROM AUTHOR]

Summary This study retrospectively compared outcomes of various allogeneic haematopoietic cell transplantation (allo‐HCT) platforms in patients with adult T‐cell leukaemia/lymphoma. Platforms included human leukocyte antigen (HLA)‐haploidentical‐related donors using post‐transplant cyclophosphamide (PTCY), HLA‐matched related donors (MRD), HLA‐matched unrelated donors (MUD) and cord blood transplantation (CBT). Patients who underwent their first allo‐HCT between 2016 and 2021 were included. Outcomes analysed were overall survival (OS), relapse and non‐relapse mortality (NRM). Seven hundred patients were included (PTCY, n = 121; MRD, n = 91; MUD, n = 160; CBT, n = 328). With a median follow‐up of 794 days for survivors, 2‐year OS was 48.1% (PTCY), 48.8% (MRD), 48.4% (MUD) and 34.6% (CBT); the respective 2‐year cumulative incidence of relapse was 37.1%, 47.5%, 33.9% and 45.1% and that of NRM was 24.2%, 19.8%, 24.7% and 27.3%. PTCY was associated with delayed platelet engraftment relative to MRD and MUD. There was no increase in the incidence of severe acute or chronic graft‐versus‐host disease. In the PTCY group, poor performance status was a significant predictor of inferior OS, and infused CD34+ cell numbers of less than 5 × 106/kg were associated with delayed neutrophil and platelet engraftment. These results suggest that allo‐HCT with PTCY is a safe and effective platform for patients with adult T‐cell leukaemia/lymphoma. [ABSTRACT FROM AUTHOR]

Summary: Background: High‐dose post‐transplant cyclophosphamide allows safe and effective use of allografts from haploidentical relatives (siblings, parents and children) in patients undergoing allogeneic blood or marrow transplant (alloBMT). More recently, second‐ and third‐degree relatives have also been shown to be safe allograft donors. An increasing number of older patients undergoing alloBMT have been receiving allografts from haploidentical donors. However, older patients are more likely to have older siblings and children, and older donor age is associated with worse outcomes. Objective: In the current study, we report the safety and utility of grandchildren as haploidentical donors and compared with children as donors in patients undergoing alloBMT. Methods: We compared characteristics and outcomes of alloBMT patients aged 55 years and older with children older than 30 years as donors (C group; n = 276) and those with grandchildren as donors (GC group; n = 40). Because many important baseline characteristics predict outcomes after alloBMT, we performed propensity score matched analysis based on recipient age, alloBMT year, disease, graft source and haematopoietic cell transplantation comorbidity index (HCT‐CI). Results: The median age of recipients was 67 years (range 55–79) in the C group and 73 years (range 57–78) in the GC group. More than 70% of recipients in the GC group were older than 70 years, compared with 27% in the C group. The median donor age was 37 years (range 31–52) in the C group and 20 years (range 14–34) in the GC group. More patients in the GC group had HCT‐CI scores ≥3 than in the C group (32.5% vs. 23%, p = 0.27). Two‐year overall survival did not differ between the two groups (GC 62% vs. C 60%, hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.53–1.75, p = 0.90) despite recipients of allografts from grandchildren being older. The 2‐year RFS was 55% in the C group compared with 50% in the GC group (HR 1.05, 95% CI 0.62–1.77, p = 0.85). Non‐relapse mortality subdistribution [SD] (SDHR 1.36, 95% 0.70–2.63, p = 0.36), relapse (SDHR 0.72, 95% CI 0.33–1.58, p = 0.42) or relapse‐free survival (HR 1.05, 95% CI 0.62–1.77, p = 0.85). Propensity score matching analysis showed no significant differences in 2‐year overall survival (GC 64% vs. C 53%; HR 0.77, 95% CI 0.42–1.42, p = 0.40), non‐relapse mortality (SDHR 1.26, 95% 0.66–2.41, p = 0.48), relapse (SDHR 0.57, 95% CI 0.21–1.52, p = 0.26) or relapse‐free survival (HR 0.94, 95% CI 0.57–1.54, p = 0.81). Conclusion: Our results indicate that outcomes of alloBMT patients with grandchild donors are similar to those with child donors, despite recipients' older age and higher comorbidities in the GC group. Grandchildren should be considered when selecting a donor for older alloBMT recipients. [ABSTRACT FROM AUTHOR]

Objective: This retrospective single center study aims to describe changes in the severity and organ‐specific distribution of GvHD, by comparing the outcomes of 3 distinct GvHD prophylaxis approaches. Methods: Between January 2012 and June 2022, 226 patients underwent allogeneic hematopoietic stem cell transplantation from HLA‐matched or 1‐allele mismatched related or unrelated donors. Fifty‐eight (26%) received prophylaxis with calcineurin inhibitor in combination with mycophenolate mofetil or a short course of methotrexate (Cohort‐1), 87 (38%) tacrolimus plus sirolimus (Cohort‐2), and 81 (36%) post‐transplant cyclophosphamide (PTCy) plus tacrolimus (Cohort‐3). Results: The incidence of grade II‐IV aGvHD was 69% vs. 41.4% vs. 27.2%; p <.01. The most significant reduction with PTCy was observed in both stage 3–4 skin and lower gastrointestinal (GI) involvement (p <.01). The incidence of moderate‐to‐severe cGvHD at 12 months was 34.5% vs. 34.5% vs. 6.2%; p <.01. Moderate‐to‐severe skin and GI cGvHD was less common after PTCy (p <.01). The 1‐year GvHD‐free/relapse‐free survival was higher with PTCy (p <.01). Conclusions: Our study indicates that PTCy‐based GvHD prophylaxis reduces the frequency and severity of both acute and chronic GvHD, with a notable decrease in severe GI and cutaneous manifestations. The higher GRFS may result in lower GvHD‐related mortality, leading to an improved quality of life among survivors. [ABSTRACT FROM AUTHOR]

This study evaluates the feasibility of using post‐transplant cyclophosphamide (PTCY) prophylaxis in allo‐hematopoietic cell transplantation (HCT) for adults aged 65 and older. PTCY is increasingly used to prevent graft‐versus‐host disease (GVHD) across all donor types, but concerns remain about potential risks, especially in older patients. Fifty‐seven adults aged 65 or older with hematological malignancies, undergoing their first allo‐HCT with PTCY prophylaxis between January 2011 and January 2023 were included. Overall, 94.8% of patients achieved primary engraftment. The median durations for neutrophil and platelet engraftments were 19 and 21 days. The day +30 cumulative incidence of bacterial bloodstream infection was 43.9%. No CMV reactivations occurred within the first 100 days after letermovir implementation. The day +180 cumulative incidences of grade II–IV and III–IV acute GVHD, and the 2‐year cumulative incidence of moderate/severe chronic GVHD were 26.3%, 10.5%, and 4.8%. Eighteen patients (31.6%) relapsed, and 30 (52.6%) died, with relapse (16.4%) and infection (11.5%) being the main causes of death. The estimated 2‐year overall survival, non‐relapse mortality, cumulative incidence of relapse, and GVHD‐free relapse‐free survival rates were 45.5%, 27.1%, 33.9%, and 37.0%. Adults aged 70 or older had similar outcomes to those aged 65–69. This study confirms the safety and feasibility of PTCY‐based allo‐HCT in older adults. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to assess the efficacy of dual T-cell suppression using individually tailored doses of antithymocyte globulin (ATG) and attenuated dose of post-transplant cyclophosphamide (PTCy) in haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We conducted a retrospective analysis of 78 adults with acute leukemia or myelodysplastic syndrome who underwent haplo-HSCT using intravenous busulfan and fludarabine conditioning. Thirty-two patients received attenuated ATG/PTCy, while 46 patients received ATG (7.5 mg/kg) as GVHD prophylaxis. The 100-day cumulative incidence of grade III-IV (9.7% vs. 32.4%, P = 0.018) acute GVHD, as well as 2-year moderate-severe chronic GVHD (13.9% vs. 43.9%, P = 0.018) in the ATG/PTCy group were significantly lower than those in the ATG group. The 2-year overall survival was comparable between the two groups. However, 2-year GVHD-free, relapse-free survival in the ATG/PTCy group was significantly higher compared to that in the ATG group (38.9% vs. 21.7%, P = 0.021). Moreover, during post-engraftment period, the ATG/PTCy group exhibited lower incidences of life-threatening bacterial (12.5% vs. 37%, P = 0.033) and viral infection (0% vs. 17.4%, P = 0.035) than the ATG group. In conclusion, the combination of individually tailored ATG and low-dose PTCy appears to be a promising strategy in haplo-HSCT.

Background: Conditioning regimens and the choice of immunosuppression have substantial impact on immune reconstitution after allogeneic hematopoietic stem cell transplantation (aHSCT). The pivotal mechanism to maintain remission is the induction of the graft‐versus‐tumor effect. Relapse as well as graft versus host disease remain common. Classic immunosuppressive strategies implementing calcineurin inhibitors (CNI) have significant toxicities, hamper the immune recovery, and reduce the anti‐cancer immune response. Methods: We designed a phase II clinical trial for patients with relapsed and refractory lymphoid malignancies undergoing aHSCT using a CNI‐free approach consisting of post‐transplant cyclophosphamide (PTCy) and short‐term Everolimus after reduced‐intensity conditioning and matched peripheral blood stem cell transplantation. The results of the 19 planned patients are presented. Primary endpoint is the cumulative incidence and severity of acute GvHD. Results: Overall incidence of acute GvHD was 53% with no grade III or IV. Cumulative incidence of NRM at 1, 2, and 4 years was 11%, 11%, and 16%, respectively, with a median follow‐up of 43 months. Cumulative incidence of relapse was 32%, 32%, and 42% at 1, 2, and 4 years after transplant, respectively. Four out of six early relapses were multiple myeloma patients. Overall survival was 79%, 74%, and 62% at 1, 2, and 4 years. GvHD‐relapse‐free‐survival was 47% after 3 years. Conclusions: Using PTCy and short‐term Everolimus is safe with low rates of aGvHD and no severe aGvHD or cGvHD translating into a low rate of non‐relapse mortality. Our results in this difficult to treat patient population are encouraging and warrant further studies. [ABSTRACT FROM AUTHOR]

Simple Summary: High-dose post-transplant cyclophosphamide is effective in preventing graft-versus-host disease (GVHD) but is associated with adverse outcomes such as delayed engraftment, infections, and cardiac issues. This pilot study evaluated the efficacy and toxicity of reduced-dose PTCY (40 mg/kg/day) in patients undergoing HLA-matched allogeneic hematopoietic stem cell transplantation (alloHSCT). Neutrophil and platelet engraftment occurred at medians of 15 and 16 days, respectively. At day 100, the incidences of grade II–IV and III–IV acute GVHD were 18.2% and 4.5%, respectively, with no cases of grade IV acute GVHD or steroid-refractory disease. One-year incidence of moderate-severe chronic GVHD was 6.4%. Both incidences, acute GVHD and chronic GVHD, are similar to our previous experience with higher doses of PTCY. Two-year overall survival and relapse-free survival were 77.1% and 58.3%. There were low incidences of infections and only one early cardiac event. These results suggest that reduced-dose PTCY provides adequate immunosuppression with a low toxicity profile. PTCY 50 mg/kg/day on days +3/+4 is an excellent strategy to prevent GVHD. However, its use is associated with adverse outcomes such as delayed engraftment, increased risk of infection, and cardiac complications. This pilot study evaluates the efficacy and toxicity of a reduced dose of PTCY (40 mg/kg/day) combined with tacrolimus in 22 peripheral blood HLA-matched alloHSCT patients. At day +100, the cumulative incidences of grade II–IV and III–IV acute GVHD were 18.2% and 4.5%, respectively. No grade IV acute GVHD or steroid-refractory disease was observed. The cumulative incidences of all-grade and moderate-severe chronic GVHD at 1-year were 11.4% and 6.4%, respectively. No patient died from transplant-related complications. Two-year OS and RFS were 77.1% and 58.3%, respectively. All patients engrafted, with neutrophil and platelet recovery occurring at a median of 15 (IQR 14–16) and 16 days (IQR 12–23), respectively. The cumulative incidences of bloodstream bacterial infections, polyomavirus BK hemorrhagic cystitis, HHV6 reactivation, CMV reactivation, and fungal infections were 13.6%, 9.1%, 9.1%, 4.6%, and 6%, respectively. Only one early cardiac event was observed. These results suggest that PTCY 40 mg/kg/day on a +3/+4 schedule provides adequate immunosuppression to allow for engraftment and prevent clinically significant GVHD with a low toxicity profile. [ABSTRACT FROM AUTHOR]

With the success of post-transplant cyclophosphamide based platform and improved clinical care, the number of haploidentical stem cell transplants (HaploSCT) have surged over the last decade. However, data from India is scarce. We aimed to evaluate the outcome of haploSCT at our centre. Since the inception of government schemes, many patients at our centre are able to undergo transplantation at subsidized cost. We conducted a retrospective analysis of the haploidentical transplants performed between January 2015 and November 2022. Fifty patients were eligible for this study. Patient details were obtained from case files. The graft versus host disease (GVHD) prophylaxis was post-transplant Cyclophosphamide (PTCy) with Mycophenolate-mofetil and Cyclosporine/tacrolimus/sirolimus. All patients were transfused peripheral blood stem cells from donors. Post-transplant, patients continued regular follow up as per schedule. Supportive care was given as per unit protocol. Overall survival (OS) was calculated using the Kaplan–Meier method. Fifty patients underwent haploSCT. A total of fifty patients with a median age of 20 years (range 3–53 years) underwent haploidentical HSCT from a family donor. Twenty three (46%) patients were > 18 years age and 82% were males. Indications for transplant included both benign and malignant hematological diseases. Most common conditioning regimen used was Fludarabine + Busulphan + Cyclophosphamide (n = 38, 76%). Thirty five patients (70%) engrafted successfully. In the patients who had successful engraftment, the median time to neutrophil engraftment was 16 days (range 10–20 days) and platelet engraftment was 18 days (range 10–32). Fourteen patients developed acute GVHD (28%), and three patients developed chronic GVHD (6%). The median follow-up was 30 months and the two-year OS was 43% with a median OS of 17 months. Twenty-one (adult = 9, pediatric = 12) out of 50 patients (42%) are alive and on regular follow-up. HaploSCT with a PTCy platform is a cost-effective, promising modality of treatment in patients who have no suitable matched donors and are not affording matched unrelated transplants. At our centre, we were able to achieve acceptable results with use of generic medications at affordable cost. Transplant Related Mortality (TRM) rates were comparable to other centres, however, multi-drug resistant bacterial infection remains a challenge in performing haploidentical HSCT in developing countries. [ABSTRACT FROM AUTHOR]

Haploidentical hematopoietic stem cell transplantation (haplo‐HCT) is an appropriate option when an HLA-matched related or unrelated donor is not available. Haplo-HCT using post-transplant cyclophosphamide (PTCy) is being increasingly performed worldwide due to its effective suppression of GVHD and its safety. We conducted a large nationwide cohort study to retrospectively analyze 366 patients with acute myeloid leukemia undergoing haplo‐HCT with PTCy between 2010 and 2019 and to identify prognostic factors. A multivariate Cox analysis revealed that an older recipient age (≥60 years), a male donor to a male recipient, a cytomegalovirus IgG-negative donor to a cytomegalovirus IgG-positive recipient, a poor cytogenetic risk, a noncomplete remission status at the time of transplantation, and a history of HCT were independently associated with worse overall survival (OS). Based on each hazard ratio, these factors were scored (1–2 points) and stratified by their total score into three groups: favorable (0–1 points), intermediate (2–3 points), and poor (4 points or more) groups, and 2-year OS rates were 79.9%, 49.2%, and 25.1%, respectively (P < 0.001). The present study revealed significant prognostic factors in haplo‐HCT with PTCy, and a scoring system based on these factors may be used to predict outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy associated with a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) has emerged as a potential treatment strategy for BPDCN, standardized conditioning regimens remain lacking. In this manuscript, we present two cases of BPDCN that were treated with a thiotepa-busulfan-fludarabine (TBF)-based conditioning regimen prior to allo-HSCT. Both cases demonstrated complete remission post-transplantation, sustained donor chimerism, and remission maintenance, suggesting the potential efficacy of the TBF conditioning regimen for BPDCN transplantation. Given the small sample size in our study, we emphasize caution and advocate for larger studies to confirm the efficacy of TBF in the treatment of BPDCN. [ABSTRACT FROM AUTHOR]

ABSTRACTIntroduction The likelihood of finding HLA-matched unrelated donors for rare HLA types and non-white European ancestry continues to be a challenge with less than a 70% chance of finding a full match. Mismatched transplants continue to have high rates of transplant-related mortality. With the near-universal ability to find a haploidentical donor in families, haploidentical transplants have become of more critical importance in ethnic minority groups and patients with rare HLA types.Methods Data was collected through clinical trials, review articles, and case reports published in the National Library of Medicine.Results The use of improved lymphodepleting conditioning regimens, graft versus host disease (GVHD) prophylaxis using regimens such as post-transplant cyclophosphamide, mycophenolate, and tacrolimus have improved engraftment to nearly 100 percent and reduced transplant-related mortality to less than 20 percent. Attention to donor-specific antibodies (DSAs) with interventions using bortezomib, rituximab, and plasmapheresis has decreased graft failure rates.Conclusion With improved prevention of GVHD with interventions such as post-transplant cyclophosphamide and management of DSAs, haploidentical transplants continue to improve transplant-related mortality (TRM) compared to patients who received matched-related donor transplants. While TRM continues to improve, ongoing research with haploidentical transplants will focus on improving graft and donor immunosuppression and identifying the best regimens to improve TRM without compromising relapse-free survival.

ABSTRACTBackground One major limitation for broader applicability of allogeneic hematopoietic cell transplantation (allo-HCT) in the past was the lack of HLA-matched histocompatible donors. Preclinical mouse studies using T-cell depleted haploidentical grafts led to an increased interest in the use of ex vivo T-cell depleted (TCD) haploidentical allo-HCT. TCD grafts through negative (T-cell depletion) or positive (CD34+ cell selection) techniques have been investigated to reduce the risk of graft-versus-host disease (GVHD) given the known implications of alloreactive T cells. A more practical approach to deplete alloreactive T cells in vivo using high doses of cyclophosphamide after allografting has proved to be feasible in overcoming the HLA barrier. Such approach has extended allo-HCT feasibility to patients for whom donors could not be found in the past. Nowadays, haploidentical donors represent a common donor source for patients in need of an allo-HCT. The broad application of haploidentical donors became possible by understanding the importance of depleting alloreactive donor T cells to facilitate engraftment and reduce incidence and severity of GVHD. These techniques involve ex vivo graft manipulation or in vivo utilization of pharmacologic agents, notably post-transplant cyclophosphamide (PTCy).Discussion While acknowledging that no randomized controlled prospective studies have been yet conducted comparing TCD versus PTCy in haploidentical allo-HCT recipients, there are two advantages that would favor the PTCy, namely ease of application and lower cost. However, emerging data on adverse events associated with PTCy including, but not limited to cardiac associated toxicities or increased incidence of post-allograft infections, and others, are important to recognize.

Summary: Haploidentical haematopoietic cell transplantation (haplo‐HCT) using post‐transplant cyclophosphamide (PTCY) as graft‐versus‐host disease (GVHD) prophylaxis is the standard of care for various haematological malignancies. The original PTCY dose after haplo‐HCT was 100 mg/kg, but no dose‐finding studies have been performed to identify the optimal dose. We performed a retrospective analysis to compare standard‐dose PTCY (100 mg/kg) with reduced‐dose PTCY (80 mg/kg): 969 in the standard‐dose group and 538 in the reduced‐dose group. As there was a significant difference between the two groups regarding patient and transplant characteristics, we performed propensity score (PS) matching. After PS matching, 425 patients in each group were included. The probabilities of 2‐year OS were 55.9% in the standard‐dose group and 47.0% in the reduced‐dose group (p = 0.36). The cumulative incidences of 2‐year non‐relapse mortality were 21.3% in the standard‐dose group and 20.5% in the reduced‐dose group (p = 0.55). There was no significant difference in the incidence of acute (grade II–IV 29.2% [95% CI, 24.9–33.6] vs. 25.3% [95% CI, 21.3–29.6]; grade III–IV 7.3% [95% CI, 5.1–10.0] vs. 6.6% [95% CI, 4.5–9.3]) or chronic GVHD. In conclusion, reduced‐ and standard‐dose PTCY were comparable in terms of major clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Donor haematopoietic stem cell transplantation treats leukaemia by inducing graft‐versus‐leukaemia (GVL) immunity. However, this benefit is often mitigated by graft‐versus‐host disease (GVHD), which is reduced by post‐transplant cyclophosphamide (PTCy) alone or combined with tocilizumab (TOC) in humanised mice. This study established a preclinical humanised mouse model of GVL and investigated whether PTCy alone or combined with TOC impacts GVL immunity. Methods: NOD‐scid‐IL2Rγnull mice were injected with 2 × 107 human peripheral blood mononuclear cells (hPBMCs) on day 0 and with 1 × 106 THP‐1 acute myeloid leukaemia cells on day 14. In subsequent experiments, mice were also injected with PTCy (33 mg kg−1) or Dulbecco's phosphate buffered saline (PBS) on days 3 and 4, alone or combined with TOC or control antibody (25 mg kg−1) twice weekly for 28 days. Clinical signs of disease were monitored until day 42. Results: Mice with hPBMCs from three different donors and THP‐1 cells showed similar survival, clinical score and weight loss. hCD33+ leukaemia cells were minimal in mice reconstituted with hPBMCs from two donors but present in mice with hPBMCs from a third donor, suggesting donor‐specific GVL responses. hPBMC‐injected mice treated with PTCy alone or combined with TOC (PTCy + TOC) demonstrated prolonged survival compared to control mice. PTCy alone and PTCy + TOC‐treated mice with hPBMCs showed minimal hepatic hCD33+ leukaemia cells, indicating sustained GVL immunity. Further, the combination of PTCy + TOC reduced histological damage in the lung and liver. Conclusion: Collectively, this research demonstrates that PTCy alone or combined with TOC impairs GVHD without compromising GVL immunity. [ABSTRACT FROM AUTHOR]

Simple Summary: Human leukocyte antigen (HLA)–haploidentical haematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide (PTCY) for haematological malignancies is an HSCT modality that has become widespread worldwide in the last 20 years and is also widely used in children. Haplo-HSCT with PTCY in adult patients with haematologic malignancies has comparable outcomes with HLA-matched unrelated donor HSCT. This review article comprehensively describes the current progress in haplo-HSCT with PTCY for paediatric haematological malignancies. The current state and future directions for donor selection (sex, age, ABO blood type, and HLA disparity), donor source, the dose of infused CD34+ cells, optimal conditioning, and the concomitant graft-versus-host disease prophylaxis other than PTCY are also extensively discussed. These aspects present key solutions for further improvements in the outcomes of haplo-HSCT with PTCY for paediatric haematological malignancies. The use of human leukocyte antigen (HLA)–haploidentical haematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PTCY), which markedly reduces the risk of graft-versus-host disease, has rapidly increased worldwide, even in children. It was initially developed for post-transplant relapse or non-remission at transplant for patients with high-risk haematologic malignancies. However, this strategy is currently used more frequently for standard-risk, transplant-eligible paediatric haematological malignancies. It has recently been recognised in adults that the transplant outcomes after PTCY-based HLA–haploidentical HSCT are comparable with those achieved after HLA-matched HSCT. Therefore, even in children, parental donors who are HLA–haploidentical donors and cord blood are currently considered the next donor candidates when an HLA-matched related or unrelated donor is unavailable. This review addresses the current status of the use of haplo-HSCT with PTCY for paediatric haematologic malignancies and future directions for donor selection (sex, age, ABO blood type, and HLA disparity), donor source, the dose of infused CD34+ cells, optimal conditioning, the concomitant graft-versus-host disease prophylaxis other than PTCY, and the pharmacokinetic study of CY and CY metabolites. These aspects present key solutions for further improvements in the outcomes of haplo-HSCT with PTCY for paediatric haematological malignancies. [ABSTRACT FROM AUTHOR]

Allogeneic haematopoietic stem cell transplantation (HSCT) leads to the establishment of graft-versus-leukaemia (GVL) immunity, but in many cases also results in the development of graft-versus-host disease (GVHD). This study aimed to determine if P2X7 antagonism using Brilliant Blue G (BBG) could improve the beneficial effects of post-transplant cyclophosphamide (PTCy) in a humanised mouse model of GVHD, without comprising GVL immunity. NOD.Cg-Prkdcscid Il2rgtm1Wjl (NSG) mice were injected with human peripheral blood mononuclear cells (PBMCs) (Day 0), then with cyclophosphamide (33 mg/kg) on Days 3 and 4, and with BBG (50 mg/kg) (or saline) on Days 0–10. PTCy with BBG reduced clinical GVHD development like that of PTCy alone. However, histological analysis revealed that the combined treatment reduced liver GVHD to a greater extent than PTCy alone. Flow cytometric analyses revealed that this reduction in liver GVHD by PTCy with BBG corresponded to an increase in human splenic CD39+ Tregs and a decrease in human serum interferon-γ concentrations. In additional experiments, humanised NSG mice, following combined treatment, were injected with human THP-1 acute myeloid leukaemia cells on Day 14. Flow cytometric analyses of liver CD33+ THP-1 cells showed that PTCy with BBG did not mitigate GVL immunity. In summary, PTCy combined with BBG can reduce GVHD without compromising GVL immunity. Future studies investigating P2X7 antagonism in combination with PTCy may lead to the development of novel treatments that more effectively reduce GVHD in allogeneic HSCT patients without promoting leukaemia relapse. [ABSTRACT FROM AUTHOR]

Introduction: The data on post‐transplant cyclophosphamide (PTCy) in pediatric acute leukemia after matched allo‐HSCT are limited to case series. The present study aimed to assess the results of PTCy‐based GVHD prophylaxis in a large cohort of children with acute leukemia after matched allo‐HSCT. Methods: A retrospective analysis of 190 pediatric patients with acute leukemia who had a first allograft between 2008 and 2020 from a matched sibling donor (MSD) or matched unrelated donor (MUD) was carried out. In the MSD setting, GVHD prophylaxis consisted of PTCy alone (n = 28) for the study group, and calcineurin inhibitor (CNI) ± antimetabolite (n = 30) for the control group. In MUD setting, most patients in the study group received GVHD prophylaxis with PTCy+CNI+mycophenolate mofetil (n = 42, 66.7%) or PTCy+CNI+sirolimus (n = 12, 19%). All patients (n = 69) in the control group received ATG+CNI+antimetabolite. Results: After MUD allo‐HSCT, the incidences of acute GVHD grade III‐IV and moderate/severe chronic GVHD were significantly lower in the PTCy group compared to control (6.6% vs. 35.0% and 12.7% vs. 47.1%, respectively, p <.0001). Five‐year GVHD‐free, relapse‐free survival (GRFS) after MUD allo‐HSCT was higher in the PTCy group compared to control (35.1% vs. 7.3%, p <.0001). At the same time, there was no significant difference between both groups after MSD allo‐HSCT. Conclusions: In pediatric acute leukemia, PTCy‐based GVHD prophylaxis for MUD allo‐HSCT is a feasible and effective option that results in a low incidence of GVHD. Compared to the ATG‐based approach, PTCy provides better control of GVHD in children. In pediatric allo‐HSCT from MSD, PTCy demonstrates comparable effectiveness to conventional GVHD prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Memory T cells are a heterogeneous population of immune cells that provide adaptive immunity. Its full recovery seems essential for graft-versus-tumor reactions that provide an opportunity for biological cure in patients with acute leukemia. The use of mismatched or haploidentical donors has increased, which has become possible because of modifications in graft versus host disease (GVHD) prophylaxis. Materials and Methods: Sixty-five leukemia patients (acute myeloid leukemia -- 40, acute lymphoblastic leukemia -- 25), median age 33 (17-61) years, underwent allo-HSCT from 2016 to 2019 in the National Research Centre for Hematology. Patients were divided into three groups based on the impact of GVHD prophylaxis on T cell recovery: horse antithymocyte globulin (ATG)-based regimen (n=32), horse ATG combined with posttransplant cyclophosphamide (PT-Cy) (n=18), and ex vivo T cell depletion (n=15). Results: The early period after transplantation (before day +100) was characterized by significantly lower absolute numbers of T naïve, memory stem and T central memory cells in peripheral blood in patients after ATG+PT-Cy-regimen or ex vivo T cell depletion than after ATG-based prophylaxis (p<0.05). Moreover, strong depletion of naïve T and memory stem cells prevents the development of GVHD, and determining the absolute number of CD8+ naïve T and memory stem cells with a cutoff of 1.31 cells per microliter seems to be a perspective in assessing the risks of developing acute GVHD (p=0.008). The dynamics of T cell recovery showed the involvement of either circulating or bone marrow resident T effector cells shortly after allogeneic transplantation in all patients, but the use of manipulated grafts with ex vivo T cell depletion requires the involvement of naïve and memory stem cells. There was no significant effect of T cell recovery on leukemia relapse after allogeneic transplantation. Conclusion: These experimental outcomes contribute to providing the best understanding of immunological events that occur early after transplantation and help in the rational choice of GVHD prophylaxis in patients who will undergo allogeneic transplantation. Our study demonstrated the comparable immunological effects of posttransplant cyclophosphamide and ex vivo T cell depletion and immunological inefficiency of horse ATG for GVHD prevention. [ABSTRACT FROM AUTHOR]

Post-transplant cyclophosphamide (PTCY)-based prophylaxis is becoming widespread for allogeneic hematopoietic cell transplantation (allo-HCT) performed independently of the selected donor source. In parallel, use of the Endothelial Activation and Stress Index (EASIX)—considered a surrogate parameter of endothelial activation—for predicting patient outcomes and clinical complications is gaining popularity in the allo-HCT setting. We first investigated whether the dynamics of EASIX after allo-HCT differ between patients receiving PTCY and patients receiving other prophylaxis. We then investigated whether the predictive capacity of EASIX persists in PTCY-based allo-HCT. A total of 328 patients transplanted between 2014 and 2020 were included, and 201 (61.2%) received PTCY. EASIX trends differed significantly between the groups. Compared with patients receiving other prophylaxis, patients receiving PTCY had lower EASIX on day 0 and higher values between day 7 and day 100. In patients receiving PTCY, higher EASIX correlated significantly with higher non-relapse mortality (NRM) and lower overall survival (OS) when measured before and during the first 180 days after allo-HCT. In addition, higher EASIX scores measured at specific time points were predictors of veno-occlusive disease (VOD), transplant-associated thrombotic microangiopathy (TA-TMA) and grade 2–4 acute graft-versus-host disease (aGVHD) risk. This study demonstrates how EASIX trends vary during the first 180 days after allo-HCT in patients receiving PTCY and those not receiving PTCY and validates the utility of this index for predicting NRM, OS and risk of VOD, TA-TMA and grade 2–4 aGVHD in patients receiving PTCY. [ABSTRACT FROM AUTHOR]

The current study includes all consecutive patients (N = 484) who received a reduced-intensity conditioning regimen (RIC) allogeneic hematopoietic stem cell transplantation in our center from 1999 to 2020. Conditioning regimens were based on fludarabine with melphalan or busulfan, with low-dose thiotepa and pharmacological GVHD prophylaxis consisted of cyclosporine A (CsA)-methotrexate (MTX)/mofetil (MMF) (n = 271), tacrolimus-sirolimus (n = 145), and post-transplantation cyclophosphamide (PTCy)-tacrolimus (n = 68). The median time of overall follow-up in survivors was 8 years (1–22 years) and was at least 3 years in all three GVHD prophylaxis groups. Thirty-three percent had a high or very high disease risk index, 56% ≥ 4 European bone marrow transplantation risk, and 65% ≥ 3 hematopoietic stem cell transplantation comorbidity index score-age score. Neutrophil and platelet engraftment was longer for PTCy-tacro (p 0.0001). Cumulative incidence of grade III–IV aGVHD was 17% at 200 days, and that of moderate-severe cGvHD was 36% at 8 years. GVHD prophylaxis was the only prognostic factor in the multivariable analyses for the development of aGVHD and moderate-severe cGVHD (p 0.0001). NRM and relapse incidences were 29% and 30% at 8 years, while OS and PFS rates were 43% and 39% at 8 years. At 3 years, OS was highest in the PTCy-tacro group (68%) than in the tacro-siro (61%) and CsA-MTX/MMF (49%) cohorts (p < 0.01). In the three groups, respectively, the 200-day incidence of grade III–IV aGvHD (6% vs. 12% vs. 23%) and 3-year moderate-severe cGVHD (8% vs. 40% vs. 38%) were lower in the PTCy cohort. These better outcomes were confirmed in multivariable analyses. Based on our recent results, the PTCy could be considered as a real GvHD prophylaxis in the RIC setting due to improve best 3-year GvHD and survival outcomes. [ABSTRACT FROM AUTHOR]

T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive disease with a poor prognosis. Allogeneic stem cell transplantation (allo-SCT) followed by alemtuzumab administration is the most promising treatment for T-PLL but is associated with a high risk of infections as alemtuzumab strongly suppresses cellular immunity, leading to high transplant-related mortality and unsatisfactory survival rates. In addition, for patients without human leukocyte antigen-matched donors, haploidentical stem cell transplantation (haplo-SCT) using post-transplant cyclophosphamide (PTCy) has been used because of the ready availability of donors and achievement of results comparable to those of transplantation with human leukocyte antigen-matched donors. However, there are no reports on the efficacy and safety, including infectious complications, of haplo-SCT with PTCy after alemtuzumab therapy in patients with. Here, we describe a 66-year-old Japanese male patient with T-PLL treated successfully with haplo-SCT after induction therapy of alemtuzumab for T-PLL. Approximately 3 months after the achievement of complete remission with alemtuzumab for T-PLL, haplo-SCT with reduced-intensity conditioning and PTCy was performed. Infectious complications were improved by early therapeutic interventions, and peripheral T cell counts gradually recovered. The patient was alive for more than 16 months after allo-SCT with no signs of relapse. Thus, haplo-SCT using PTCy should be considered as an option after alemtuzumab treatment for T-PLL.

Abstract Background KIR/HLA mismatch in hematopoietic stem cell transplantation (HSCT), particularly in patients with acute myeloid leukemia (AML), was related to decreased recurrence rates, improved engraftment, and a reduction in graft-versus-host disease, according to recent research (GVHD). Uncertainty exists about the impact of KIR/HLA mismatch on haploidentical-HSCTs treated with post-transplant cyclophosphamide (PTCy). We attempted to analyze the effects of KIR/HLA mismatch on clinical outcomes on transplant outcomes using the cohort of 54 AML patients who received a haplo-HSCT with PTCy. Results In contrast to KIR/HLA match, our findings showed that donor KIR/HLA mismatch was substantially associated with superior OS (HR, 2.92; (P = 0.04)). Moreover, donor KIR/HLA mismatch (KIR2DS1D/C2+ R and KIR2DS2D/C1+ R mismatch versus KIR2DL1D/C2− R mm, KIR2DL2/3D/C1− R mm and KIR3DL1D/Bw4− mm) was correlated with the improvements in OS (HR, 0.74; P = 0.085) and activating. KIR/HLA mismatch versus KIR/HLA match was significantly correlated with improvements in OS (HR, .46; P = 0.03) and inhibitory. KIR/HLA mismatch versus KIR/HLA match was enhancement in the OS (HR, .93; P = 0.06). Despite a higher rate of aGvHD (grade I-IV) in the patients with KIR/HLA mismatch compared to KIR/HLA matched (57% vs. 33% (p = 0.04). However, the KIR/HLA mismatch group saw a decreased relapse rate (3.2% vs. 23%, p = 0.04). Conclusion This analysis shows the significance of KIR/HLA Incompatibility, other clinical variables like CMV, the relationship between donor/recipient and donor age, and the relationship between donor/recipient and donor age in the haplo-donor selection process. It also suggests that KIR and HLA mismatching between donor and recipient could be routinely performed for haplo-donor selection and may improve clinical outcomes after haplo-HSCTs with PTCy.

Abstract Objectives Donor haematopoietic stem cell transplantation treats leukaemia by inducing graft‐versus‐leukaemia (GVL) immunity. However, this benefit is often mitigated by graft‐versus‐host disease (GVHD), which is reduced by post‐transplant cyclophosphamide (PTCy) alone or combined with tocilizumab (TOC) in humanised mice. This study established a preclinical humanised mouse model of GVL and investigated whether PTCy alone or combined with TOC impacts GVL immunity. Methods NOD‐scid‐IL2Rγnull mice were injected with 2 × 107 human peripheral blood mononuclear cells (hPBMCs) on day 0 and with 1 × 106 THP‐1 acute myeloid leukaemia cells on day 14. In subsequent experiments, mice were also injected with PTCy (33 mg kg−1) or Dulbecco's phosphate buffered saline (PBS) on days 3 and 4, alone or combined with TOC or control antibody (25 mg kg−1) twice weekly for 28 days. Clinical signs of disease were monitored until day 42. Results Mice with hPBMCs from three different donors and THP‐1 cells showed similar survival, clinical score and weight loss. hCD33+ leukaemia cells were minimal in mice reconstituted with hPBMCs from two donors but present in mice with hPBMCs from a third donor, suggesting donor‐specific GVL responses. hPBMC‐injected mice treated with PTCy alone or combined with TOC (PTCy + TOC) demonstrated prolonged survival compared to control mice. PTCy alone and PTCy + TOC‐treated mice with hPBMCs showed minimal hepatic hCD33+ leukaemia cells, indicating sustained GVL immunity. Further, the combination of PTCy + TOC reduced histological damage in the lung and liver. Conclusion Collectively, this research demonstrates that PTCy alone or combined with TOC impairs GVHD without compromising GVL immunity.

We describe two young patients with Wiskott-Aldrich Syndrome (WAS) who were treated by T-replete hematopoietic stem cell transplantation (HSCT) from the HLA haploidentical father according to a modified Baltimore protocol. Whereas similar protocols have been successfully used in various malignant and non-malignant diseases, this is the first report for this particular disease. The data being presented pertains to the report about two successful haploidentical transplants with post transplant cyclophosphamide (PTCY) after busulfan-based conditioning. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation is a curative treatment for many inborn errors of immunity (IEI). Incremental improvements and advances in care have led to high rates of >85% survival and cure in many of these diseases. Improvements in HLA-classification and matching have led to increased survival using HLA-matched donors, but survival using T-lymphocyte-depleted mismatched grafts remained significantly worse until fairly recently. Advances in T-lymphocyte depletion methods and graft engineering, although not specific to IEI, have been widely adopted and instrumental in changing the landscape of donor selection, such that a donor should now be possible for every patient. A literature review focusing on T-lymphocyte depletion methodologies and treatment results was performed. The importance of early T-lymphocyte immunoreconstitution to protect against viral infection is reviewed. Two main platforms now dominate the field – immune-magnetic selection of specific cell types and post-transplant chemotherapeutic targeting of rapidly proliferating allo-reactive T-lymphocytes – the emerging literature on these reports, focusing on IEI, is explored, as well as the impact of serotherapy on early immunoreconstitution. Pharmacokinetic monitoring of serotherapy agents, and use of co-stimulatory molecule blockade are likely to become more widespread. Post-transplant cyclophosphamide or TCR depletion strategies are likely to become the dominant methods of transplantation for nonmalignant diseases. [ABSTRACT FROM AUTHOR]

Solid organ transplantation from the same donor is an established procedure for end-stage organ failure that developed after a previous hematopoietic stem cell transplantation (HSCT); however, it is rarely done in patients transplanted with unmanipulated haplo-HSCT. There are no pediatric reports regarding the long-term performance of organ transplantation after haplo-HSCT with post-transplant cyclophosphamide (PTCY). A juvenile myelomonocytic leukemia patient, who underwent unmanipulated haplo-HSCT with PTCY from her mother at the age of 3 years, developed chronic liver graft versus host disease (GvHD) which was refractory to specific GvHD treatment. Liver transplantation (LT) from her mother (the donor of her haplo-HSCT) was decided as the next line of treatment. LT was performed on day 540 post-HSCT, and the donor's left lateral segment was appropriately removed and attached to the recipient. The symptoms of GvHD completely regressed in a month. The patient died on day 121 after LT, because of a possible hepato-pulmonary syndrome. Organ failure can develop after allo-HSCT secondary to GvHD and therefore performing HSCT from a haplodonor may be superior to a matched unrelated donor in terms of subsequent organ transplantation for organ failure. [ABSTRACT FROM AUTHOR]

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). Currently, more patients can receive SCT. This is attributed to the use of reduced intensity regimens and the use of different GVHD prophylaxis that breaks the barrier of human leukocyte antigen, allowing an increase in the donor pool. Once an area with relatively few clinical trial options, there has been an increase in interest in GVHD prophylaxis and treatment, which has led to many US Food and Drug Administration (FDA) approvals. Although there is considerable excitement over novel therapies, many patients may not have access to them due to geographical or other resource constraints. In this review article, we summarize the latest evidence on how we can continue to repurpose drugs for GVHD prophylaxis and treatment. Drugs covered by our review include those that have been FDA approved for other uses for at least 15 years (since 2008); thus, they are likely to have generic equivalents available now or in the near future. [ABSTRACT FROM AUTHOR]

Graft‐versus‐host disease (GVHD) is a life‐threatening complication following donor hematopoietic stem cell transplantation, where donor T cells damage host tissues. This study investigated the effect of tocilizumab (TOC) combined with post‐transplant cyclophosphamide (PTCy) on immune cell engraftment and GVHD development in a humanized mouse model. NOD‐scid‐IL2Rγnull (NSG) mice were injected intraperitoneally with 2 × 107 human (h) peripheral blood mononuclear cells and cyclophosphamide (33 mg kg−1) or saline on days 3 and 4, then TOC or control antibody (0.5 mg mouse−1) twice weekly for 28 days. Mice were monitored for clinical signs of GVHD for either 28 or 70 days. Spleens and livers were assessed for human leukocyte subsets, and serum cytokines and tissue histology were analyzed. In the short‐term model (day 28), liver and lung damage were reduced in PTCy + TOC compared with control mice. All groups showed similar splenic hCD45+ leukocyte engraftment (55–60%); however, PTCy + TOC mice demonstrated significantly increased (1.5–2‐fold) splenic regulatory T cells. Serum human interferon gamma was significantly reduced in PTCy + TOC compared with control mice. Long‐term (day 70), prolonged survival was similar in PTCy + TOC (median survival time, > 70 days) and PTCy mice (median survival time, 56 days). GVHD onset was significantly delayed in PTCy + TOC, compared with TOC or control mice. Notably, natural killer cells were reduced (77.5%) in TOC and PTCy + TOC mice. Overall, combining PTCy with TOC increases regulatory T cells and reduces clinical signs of early GVHD, but does not improve long‐term survival compared with PTCy alone. [ABSTRACT FROM AUTHOR]

Background: KIR/HLA mismatch in hematopoietic stem cell transplantation (HSCT), particularly in patients with acute myeloid leukemia (AML), was related to decreased recurrence rates, improved engraftment, and a reduction in graft-versus-host disease, according to recent research (GVHD). Uncertainty exists about the impact of KIR/HLA mismatch on haploidentical-HSCTs treated with post-transplant cyclophosphamide (PTCy). We attempted to analyze the effects of KIR/HLA mismatch on clinical outcomes on transplant outcomes using the cohort of 54 AML patients who received a haplo-HSCT with PTCy. Results: In contrast to KIR/HLA match, our findings showed that donor KIR/HLA mismatch was substantially associated with superior OS (HR, 2.92; (P = 0.04)). Moreover, donor KIR/HLA mismatch (KIR2DS1D/C2+R and KIR2DS2D/C1+R mismatch versus KIR2DL1D/C2−R mm, KIR2DL2/3D/C1−R mm and KIR3DL1D/Bw4− mm) was correlated with the improvements in OS (HR, 0.74; P = 0.085) and activating. KIR/HLA mismatch versus KIR/HLA match was significantly correlated with improvements in OS (HR,.46; P = 0.03) and inhibitory. KIR/HLA mismatch versus KIR/HLA match was enhancement in the OS (HR,.93; P = 0.06). Despite a higher rate of aGvHD (grade I-IV) in the patients with KIR/HLA mismatch compared to KIR/HLA matched (57% vs. 33% (p = 0.04). However, the KIR/HLA mismatch group saw a decreased relapse rate (3.2% vs. 23%, p = 0.04). Conclusion: This analysis shows the significance of KIR/HLA Incompatibility, other clinical variables like CMV, the relationship between donor/recipient and donor age, and the relationship between donor/recipient and donor age in the haplo-donor selection process. It also suggests that KIR and HLA mismatching between donor and recipient could be routinely performed for haplo-donor selection and may improve clinical outcomes after haplo-HSCTs with PTCy. [ABSTRACT FROM AUTHOR]

Summary: Pre‐transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo‐HCT). The impact of MRD on the outcomes of post‐transplant cyclophosphamide (PTCy)‐based allo‐HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD−], n = 165; MRD positive [MRD+], n = 107) with a median follow‐up of 19 (range: 16–24) months were studied. The incidence of grades II–IV and grades III–IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2‐year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD− cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39–4.72), lower leukaemia‐free survival (LFS) (HR = 2.04, 95% CI: 1.23–3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04–3.25) and GVHD‐free, relapse‐free survival (GRFS) (HR = 1.69, 95% CI: 1.10–2.58). MRD status did not have a significant impact on non‐relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo‐HCT with PTCy, pre‐transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS. [ABSTRACT FROM AUTHOR]

Background: Despite the improvements in supportive care for allogeneic‐hematopoietic cell transplantation (allo‐HCT) recipients, infectious complications and infection‐related mortality (IRM) continue to be a major issue for transplantation centers. Methods: We herein report the infectious complications and IRM of 107 and 89 patients that underwent haploidentical (haplo‐HCT) or HLA‐identical HCT at a tertiary referral center during 2013‐2020. Patients in the haplo‐HCT group received post‐transplant cyclophosphamide (PT‐Cy), and all received reduced‐intensity conditioning regimens. Results: More haplo‐HCT recipients presented severe infections in the pre‐engraftment period (22.4% vs. 6.7%, p = 0.003). Viral (14.9% vs. 4.5%, p = 0.016) and fungal (12.1% vs. 1.1%, p = 0.003) etiologies were more common in this period in this group. The 100‐day and 2‐year cumulative incidence of IRM was 15% and 21% for the haplo‐HCT and 5.6% and 17% for the HLA‐identical group; no significant differences were observed between the groups. Fungal pathogens mainly contributed to IRM (33.3%). Infections were the most common cause of mortality (40/81, 49.4%). There were significant differences in donor/recipient CMV serostatus between transplant groups (0.002). Conclusions: No differences in IRM were observed based on allo‐HCT type, with more haplo‐HCT patients suffering from severe infections in the pre‐engraftment period. Studies to assess future prevention, diagnostic, and treatment strategies to reduce IRM are warranted. [ABSTRACT FROM AUTHOR]

Abstract The association between graft-versus-host disease (GVHD) occurrence and acute myeloid leukemia (AML) relapse in patients treated with HLA-haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) with post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis has remained debated. Here, we addressed this issue in patients with active AML at transplantation. 2-year cumulative incidences of relapse and leukemia-free survival (LFS) were 49% and 32.3%, respectively. There were no associations between acute nor chronic GVHD of any grade and lower relapse incidence. However, grade I acute GVHD was associated with better LFS (HR = 0.71, 95% CI 0.51–0.99, P = 0.04). In contrast, grade III–IV acute (HR = 3.09, 95% CI 1.87–5.12, P

Abstract Background Chronic active Epstein-Barr virus infection (CAEBV) is a rare but life-threatening progressive disease. Human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is the best choice as sometimes HLA-matched donor is not accessible. However, graft-versus-host-disease (GVHD) following transplantation remains a major cause of treatment failure and elevated mortality. Post-transplant cyclophosphamide (PTCy) has recently emerged for effective GVHD prophylaxis in a haploidentical setting in many hematologic malignancies. Here, we report the performance of PTCy for GVHD prophylaxis in a series of CEABV patients treated with haplo-HSCT. Methods Consecutive pediatric CAEBV patients who were treated with haplo-HSCT and give PTCy for GVHD prophylaxis were analyzed. 1-year GVHD and relapse-free survival (GRFS), overall survival (OS) and cumulative incidence of moderate-to-severe chronic GVHD (cGVHD) were estimated. Results A total of 8 patients ranging from 2 to 15 years old were included. Among them, 4 patients had early complications after haplo-HSCT. Counts of T-cell subsets increased within 6 months post transplantation, indicating an immune reconstitution. Only 1 patient developed grade II acute GVHD, and 2 patients had moderate cGVHD. One patient died from diffuse alveolar hemorrhage within the first year after transplantation. The 1-year GRFS rate, OS rate and cumulative incidence of moderate-to-severe cGVHD were 62.5%, 87.5% and 25.0%, respectively. Conclusion Our findings suggest that, among CAEBV patients treated with haplo-HSCT, PTCy may be an alternative choice for the prevention of GVHD.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT), as one of the life-saving treatments for severe aplastic anemia (SAA), is widely used because of its great donor availability. Over decades, granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG)-based protocol (the so-called Beijing Protocol) has achieved favorable engraftment and survival outcomes. In this study, we modified the conventional Beijing Protocol: the full-dose Cyclophosphamide (Cy) (200 mg/kg in total) was divided into 42.75 mg/kg Cy on day -5 to day -2 and Low dose post-transplant Cy (PTCy) (14.5 mg/kg on days +3 and +4), hoping to reduce the incidence of severe acute graft-versus-host disease (aGVHD) and to guarantee successful and stable engraftment. Here we retrospectively reported and analyzed the data of first 17 patients with SAA who had received haplo-HSCT using this novel regimen between August 2020 and August 2022. The median follow-up was 522 days (range, 138-859 days). No patient developed primary graft failure. Four (23.5%) patients developed grade II bladder toxicity, two (11.8%) patients developed grade II cardiotoxicity. All patients achieved neutrophil and platelet engraftment at median times of 12 days (range, 11–20 days) and14 days (range, 8-36 days). During our follow-up, no patients developed grade III-IV aGVHD. The cumulative incidence of grade II and grade I aGVHD at 100 days was 23.5% (95% CI, 6.8%-49.9%) and 47.1% (95% CI, 23.0%-72.2%). Three patients (17.6%) developed chronic GVHD of skin, mouth, and eyes and all of which were mild. All patients are alive by the end of the follow-up, with a failure-free survival of 100%, which was defined as survival without treatment failures, such as death, graft failure, or relapse rate. The rate of cytomegalovirus (CMV) reactivation was 82.4% (95% CI, 64.3%-100%). The rate of Epstein-Barr virus (EBV) reactivation was 17.6% (95% CI, 3.8%-43.4%). No CMV disease and post-transplantation lymphoproliferative disorder (PTLD) occurred among these patients. In conclusion, the encouraging results of prolonged survival outcomes and reduced incidence of GVHD suggest promising effect of this novel regimen in haplo-HSCT for patients with SAA. Larger-sample prospective clinical trials are needed to confirm the effectiveness of this regimen. [ABSTRACT FROM AUTHOR]

Simple Summary: Natural killer (NK) cells are key cytotoxic effectors against leukemic cells. The polymorphism of killer cell immunoglobulin-like receptor (KIR) genes plays a crucial role in the NK cell repertoire. In particular, different levels of KIR3DL1 expression on the NK cell surface are described, discriminating non-expressed vs. expressed allotypes depending on the KIR3DL1 alleles. KIR3DL1 allelic polymorphism after T-replete haploidentical hematopoietic stem cell transplantation (hHSCT) has not yet been investigated. In this study, we first assessed the extent of non-expressed versus expressed KIR3DL1 allotypes in a cohort of healthy blood donors and then evaluated their clinical impact on relapse incidence after hHSCT. Overall, we would expect that taking KIR3DL1 allelic polymorphism into consideration could help to refine the scores used for HSC donor selection. KIR3DL1 alleles are expressed at different levels on the natural killer (NK) cell surface. In particular, the non-expressed KIR3DL1*004 allele appears to be common in Caucasian populations. However, the overall distribution of non-expressed KIR3DL1 alleles and their clinical relevance after T-replete haploidentical hematopoietic stem cell transplantation (hHSCT) with post-transplant cyclophosphamide remain poorly documented in European populations. In a cohort of French blood donors (N = 278), we compared the distribution of expressed and non-expressed KIR3DL1 alleles using next-generation sequencing (NGS) technology combined with multi-color flow cytometry. We confirmed the predominance of the non-expressed KIR3DL1*004 allele. Using allele-specific constructs, the phenotype and function of the uncommon KIR3DL1*019 allotype were characterized using the Jurkat T cell line and NKL transfectants. Although poorly expressed on the NK cell surface, KIR3DL1*019 is retained within NK cells, where it induces missing self-recognition of the Bw4 epitope. Transposing our in vitro observations to a cohort of hHSCT patients (N = 186) led us to observe that non-expressed KIR3DL1 HSC grafts increased the incidence of relapse in patients with myeloid diseases. Non-expressed KIR3DL1 alleles could, therefore, influence the outcome of hHSCT. [ABSTRACT FROM AUTHOR]

Introduction: Anti-T-lymphocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy) prevent graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT), yet individual patients benefit differentially. Methods: Given the sparse comparative data on the impact of cellular immune reconstitution in this setting, we studied flow cytometry and clinical outcomes in 339 recipients of 10/10 matched-unrelated donor (MUD) HCT using either ATG (n=304) or PTCy (n=35) for in vivo T cell manipulation along with a haploidentical PTCy control cohort (n=45). Longitudinal cellular immune reconstitution data were analyzed conventionally and with a data science approach using clustering with dynamic time warping to determine the similarity between time-series of T cell subsets. Results: Consistent with published studies, no significant differences in clinical outcomes were observed at the cohort level between MUD-ATG and MUD-PTCy. However, cellular reconstitution revealed preferences for distinct T cell subpopulations associating with GVHD protection in each setting. Starting early after HCT, MUD-PTCy patients had higher regulatory T cell levels after HCT (p <0.0001), while MUD-ATG patients presented with higher levels of γδ T- or NKT cells (both p <0.0001). Time-series clustering further dissected the patient population's heterogeneity revealing distinct immune reconstitution clusters. Importantly, it identified phenotypes that reproducibly associated with impaired clinical outcomes within the same in vivo T cell manipulation platform. Exemplarily, patients with lower activated- and αβ T cell counts had significantly higher NRM (p=0.032) and relapse rates (p =0.01). Discussion: The improved understanding of the heterogeneity of cellular reconstitution in MUD patients with T cell manipulation both at the cohort and individual level may support clinicians in managing HCT complications. [ABSTRACT FROM AUTHOR]

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). Currently, more patients can receive SCT. This is attributed to the use of reduced intensity regimens and the use of different GVHD prophylaxis that breaks the barrier of human leukocyte antigen, allowing an increase in the donor pool. Once an area with relatively few clinical trial options, there has been an increase in interest in GVHD prophylaxis and treatment, which has led to many US Food and Drug Administration (FDA) approvals. Although there is considerable excitement over novel therapies, many patients may not have access to them due to geographical or other resource constraints. In this review article, we summarize the latest evidence on how we can continue to repurpose drugs for GVHD prophylaxis and treatment. Drugs covered by our review include those that have been FDA approved for other uses for at least 15 years (since 2008); thus, they are likely to have generic equivalents available now or in the near future.

Allogeneic haematopoietic stem cell transplantation (HSCT) leads to the establishment of graft-versus-leukaemia (GVL) immunity, but in many cases also results in the development of graft-versus-host disease (GVHD). This study aimed to determine if P2X7 antagonism using Brilliant Blue G (BBG) could improve the beneficial effects of post-transplant cyclophosphamide (PTCy) in a humanised mouse model of GVHD, without comprising GVL immunity. NOD.Cg-Prkdcscid Il2rgtm1Wjl (NSG) mice were injected with human peripheral blood mononuclear cells (PBMCs) (Day 0), then with cyclophosphamide (33 mg/kg) on Days 3 and 4, and with BBG (50 mg/kg) (or saline) on Days 0–10. PTCy with BBG reduced clinical GVHD development like that of PTCy alone. However, histological analysis revealed that the combined treatment reduced liver GVHD to a greater extent than PTCy alone. Flow cytometric analyses revealed that this reduction in liver GVHD by PTCy with BBG corresponded to an increase in human splenic CD39+ Tregs and a decrease in human serum interferon-γ concentrations. In additional experiments, humanised NSG mice, following combined treatment, were injected with human THP-1 acute myeloid leukaemia cells on Day 14. Flow cytometric analyses of liver CD33+ THP-1 cells showed that PTCy with BBG did not mitigate GVL immunity. In summary, PTCy combined with BBG can reduce GVHD without compromising GVL immunity. Future studies investigating P2X7 antagonism in combination with PTCy may lead to the development of novel treatments that more effectively reduce GVHD in allogeneic HSCT patients without promoting leukaemia relapse.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT), as one of the life-saving treatments for severe aplastic anemia (SAA), is widely used because of its great donor availability. Over decades, granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG)-based protocol (the so-called Beijing Protocol) has achieved favorable engraftment and survival outcomes. In this study, we modified the conventional Beijing Protocol: the full-dose Cyclophosphamide (Cy) (200 mg/kg in total) was divided into 42.75 mg/kg Cy on day -5 to day -2 and Low dose post-transplant Cy (PTCy) (14.5 mg/kg on days +3 and +4), hoping to reduce the incidence of severe acute graft-versus-host disease (aGVHD) and to guarantee successful and stable engraftment. Here we retrospectively reported and analyzed the data of first 17 patients with SAA who had received haplo-HSCT using this novel regimen between August 2020 and August 2022. The median follow-up was 522 days (range, 138-859 days). No patient developed primary graft failure. Four (23.5%) patients developed grade II bladder toxicity, two (11.8%) patients developed grade II cardiotoxicity. All patients achieved neutrophil and platelet engraftment at median times of 12 days (range, 11–20 days) and14 days (range, 8-36 days). During our follow-up, no patients developed grade III-IV aGVHD. The cumulative incidence of grade II and grade I aGVHD at 100 days was 23.5% (95% CI, 6.8%-49.9%) and 47.1% (95% CI, 23.0%-72.2%). Three patients (17.6%) developed chronic GVHD of skin, mouth, and eyes and all of which were mild. All patients are alive by the end of the follow-up, with a failure-free survival of 100%, which was defined as survival without treatment failures, such as death, graft failure, or relapse rate. The rate of cytomegalovirus (CMV) reactivation was 82.4% (95% CI, 64.3%-100%). The rate of Epstein-Barr virus (EBV) reactivation was 17.6% (95% CI, 3.8%-43.4%). No CMV disease and post-transplantation lymphoproliferative disorder (PTLD) occurred among these patients. In conclusion, the encouraging results of prolonged survival outcomes and reduced incidence of GVHD suggest promising effect of this novel regimen in haplo-HSCT for patients with SAA. Larger-sample prospective clinical trials are needed to confirm the effectiveness of this regimen.

IntroductionAnti-T-lymphocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy) prevent graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT), yet individual patients benefit differentially.MethodsGiven the sparse comparative data on the impact of cellular immune reconstitution in this setting, we studied flow cytometry and clinical outcomes in 339 recipients of 10/10 matched-unrelated donor (MUD) HCT using either ATG (n=304) or PTCy (n=35) for in vivo T cell manipulation along with a haploidentical PTCy control cohort (n=45). Longitudinal cellular immune reconstitution data were analyzed conventionally and with a data science approach using clustering with dynamic time warping to determine the similarity between time-series of T cell subsets.ResultsConsistent with published studies, no significant differences in clinical outcomes were observed at the cohort level between MUD-ATG and MUD-PTCy. However, cellular reconstitution revealed preferences for distinct T cell subpopulations associating with GVHD protection in each setting. Starting early after HCT, MUD-PTCy patients had higher regulatory T cell levels after HCT (p

Background: Post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are both common graft-versus-host disease (GVHD) prophylaxis strategies in allo-HSCT from unrelated donors. However, no consensus has reached on which regimen is optimal. Although several studies concerning this topic exist, the outcomes of different studies still conflict with each other. Therefore, an overall comparison of the two regimens is urgently needed to help make informed clinical decisions. Methods: Studies comparing PTCy and ATG regimens in unrelated donor (UD) allo-HSCT were searched in four critical medical databases from inception to April 17, 2022. The primary outcome was grade II-IV aGVHD, grade III-IV aGVHD and chronic GVHD (cGVHD), and the secondary outcomes included overall survival (OS), relapse incidence (RI), non-relapse mortality (NRM), and several severe infectious complications. The quality of articles was assessed by the Newcastle-Ottawa scale (NOS), and data were extracted by two independent investigators and then analyzed by RevMan 5.4. Results: Six out of 1091 articles were eligible for this meta-analysis. Compared with the ATG regimen, prophylaxis based on PTCy achieved a lower incidence of grade II-IV aGVHD incidence (RR=0.68, 95% CI 0.50-0.93, P=0.010, I2 = 67%), grade III-IV aGVHD (RR=0.32, 95% CI 0.14-0.76, P=0.001, I2 = 75%), NRM (RR=0.67, 95% CI 0.53-0.84, P=0.17, I2 = 36%), EBV-related PTLD (RR=0.23, 95% CI 0.09-0.58, P=0.85, I2 = 0%) and better OS (RR=1.29, 95% CI 1.03-1.62, P=0.0001, I2 = 80%). The cGVHD, RI, CMV reactivation and BKV-related HC showed no significant difference between the two groups (RR=0.66, 95% CI 0.35-1.26, P<0.00001, I2 = 86%; RR=0.95, 95% CI 0.78-1.16, P=0.37, I2 = 7%; RR=0.89, 95% CI 0.63-1.24, P=0.07, I2 = 57%; RR=0.88, 95% CI 0.76-1.03, P=0.44, I2 = 0%). Conclusion: In the setting of unrelated donor allo-HSCT, prophylaxis based on PTCy can lower the incidence of grade II-IV aGVHD, grade III-IV aGVHD, NRM and EBV-related complication, achieve better OS compared to ATG-based regimen. And cGVHD, RI, CMV reactivation and BKV-related HC were comparable in the two groups. [ABSTRACT FROM AUTHOR]

The association between graft-versus-host disease (GVHD) occurrence and acute myeloid leukemia (AML) relapse in patients treated with HLA-haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) with post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis has remained debated. Here, we addressed this issue in patients with active AML at transplantation. 2-year cumulative incidences of relapse and leukemia-free survival (LFS) were 49% and 32.3%, respectively. There were no associations between acute nor chronic GVHD of any grade and lower relapse incidence. However, grade I acute GVHD was associated with better LFS (HR = 0.71, 95% CI 0.51–0.99, P = 0.04). In contrast, grade III–IV acute (HR = 3.09, 95% CI 1.87–5.12, P < 0.0001) as well as extensive chronic (HR = 3.3, 95% CI 1.81–6.04, P = 0.0001) GVHD correlated with higher nonrelapse mortality leading to lower LFS (HR = 1.36, 95% CI 0.99–1.86, P = 0.056 and HR = 1.97, 95% CI 1.35–2.89, P = 0.0004, respectively). In conclusion, these data suggest a dissociation of graft-versus-leukemia effects from GVHD in patients with active AML treated with PTCy-based Haplo-HCT. [ABSTRACT FROM AUTHOR]

Summary: Haploidentical transplantation strategies for patients with transfusion‐dependent thalassaemia (TD‐TM) remain to be investigated. In this study, 54 paediatric patients with TD‐TM were treated with a novel approach using post‐transplant cyclophosphamide (PTCy) and low‐dose methotrexate (LD‐MTX), following a myeloablative regimen. The incidence of neutrophil and platelet engraftment was 96.3% ± 2.6% and 94.4% ± 3.1% respectively. The cumulative incidence of grades II–III acute graft‐versus‐host disease (GVHD) was 13.8% ± 4.8% at 100 days. At three years, the cumulative incidence of chronic GVHD was 28.5% ± 8.5%. With a median follow‐up of 520 days (132–1325 days), the overall survival (OS) and event‐free survival (EFS) were 98.1% ± 1.8% and 90.7% ± 3.9% respectively. Compared with the low‐dose cyclophosphamide (CTX) conditioning regimen (120 mg/kg), the high‐CTX regimen (200 mg/kg) achieved a higher incidence of stable engraftment (100% vs 66.7% ± 15.7%, p = 0.003), a comparable incidence of grades II–III acute GVHD, a lower incidence of chronic GVHD (20.2% ± 8.3% vs 66.6% ± 19.2%, p = 0.011), and better overall survival (100% vs 88.9% ± 10.5%, p = 0.025) as well as EFS (95.6% ± 3.1% vs 66.7% ± 15.7%, p = 0.008). Our results using unmanipulated haploidentical grafts and PTCy with LD‐MTX in TD‐TM are encouraging. (chictr.org.cn ChiCTR1800017969) [ABSTRACT FROM AUTHOR]

Summary: Anti‐thymocyte globulin (ATG) or post‐transplant cyclophosphamide (PTCy)‐based regimens are widely used for graft‐versus‐host disease (GVHD) prophylaxis in haploidentical haematopoietic stem cell transplantation (haplo‐HSCT). To improve the effectiveness of GVHD prophylaxis in haploidentical peripheral blood stem cell transplantation (haplo‐PBSCT), we conducted a multicentre, randomized clinical trial to determine the efficacy of reduced‐dose PTCy (40 mg/kg/d on days 3 and 4) combined with low‐dose post‐transplant ATG (2.5 mg/kg on day 8)‐based GVHD prophylaxis (reduced‐dose PTCy/ATG) with fludarabine–busulfan–cytarabine (FBA) conditioning for patients with haematological malignancies. From 2018 to 2022, 122 patients from four institutions were randomly assigned 1:1 to either a reduced‐dose PTCy/ATG or a standard‐dose ATG group ('Beijing Protocol', ATG: 10 mg/kg). All patients achieved myeloid engraftment. Cumulative incidences of grade II–IV (11.5% vs 39.3%, p = 0.001) and grade III–IV (6.6% vs 24.6%, p = 0.014) acute GVHD at day 100 were significantly reduced in the reduced‐dose PTCy/ATG group. Furthermore, two‐year overall survival, disease‐free survival and GVHD‐free/relapse‐free survival were significantly improved in the reduced‐dose PTCy/ATG group (75.4% vs 54.1%, p = 0.021; 72.7% vs 55.0%, p = 0.044; 61.3% vs 42.3%, p = 0.022 respectively). Our results demonstrate that the addition of low‐dose ATG to reduced‐dose PTCy with FBA conditioning is a promising strategy in haplo‐PBSCT. [ABSTRACT FROM AUTHOR]

T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive disease with a poor prognosis. Allogeneic stem cell transplantation (allo-SCT) followed by alemtuzumab administration is the most promising treatment for T-PLL but is associated with a high risk of infections as alemtuzumab strongly suppresses cellular immunity, leading to high transplant-related mortality and unsatisfactory survival rates. In addition, for patients without human leukocyte antigen-matched donors, haploidentical stem cell transplantation (haplo-SCT) using post-transplant cyclophosphamide (PTCy) has been used because of the ready availability of donors and achievement of results comparable to those of transplantation with human leukocyte antigen-matched donors. However, there are no reports on the efficacy and safety, including infectious complications, of haplo-SCT with PTCy after alemtuzumab therapy in patients with. Here, we describe a 66-year-old Japanese male patient with T-PLL treated successfully with haplo-SCT after induction therapy of alemtuzumab for T-PLL. Approximately 3 months after the achievement of complete remission with alemtuzumab for T-PLL, haplo-SCT with reduced-intensity conditioning and PTCy was performed. Infectious complications were improved by early therapeutic interventions, and peripheral T cell counts gradually recovered. The patient was alive for more than 16 months after allo-SCT with no signs of relapse. Thus, haplo-SCT using PTCy should be considered as an option after alemtuzumab treatment for T-PLL. [ABSTRACT FROM AUTHOR]

Tacrolimus (Tac) is a pivotal immunosuppressant agent used to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloHSCT). Tac is characterized by a narrow therapeutic window and a high inter-patient and intra-patient pharmacokinetic variability (IPV). Although high IPV of Tac concentrations has been associated with adverse post-transplant outcomes following solid organ transplantation, the effects of Tac IPV on alloHSCT recipients have not been determined. Tac IPV was therefore retrospectively evaluated in 128 alloHSCT recipients receiving high-dose post-transplant cyclophosphamide (PTCy) and the effects of Tac IPV on the occurrence of acute GVHD (aGVHD) were analyzed. Tac IPV was calculated from pre-dose concentrations (C0) measured during the first month after Tac initiation. The cumulative rates of grades II-IV and grades III-IV aGVHD at day +100 were 22.7% and 7%, respectively. Higher Tac IPV was associated with a greater risk of developing GVHD, with patients having IPV > 50th percentile having significantly higher rates of grades II-IV (34.9% vs. 10.8%; hazard ratio [HR] 3.858, p < 0.001) and grades III-IV (12.7% vs. 1.5%; HR 9.69, p = 0.033) aGVHD than patients having IPV ≤ 50th percentile. Similarly, patients with IPV > 75th percentile had higher rates of grades II-IV (41.9% vs. 16.5%; HR 3.30, p < 0.001) and grades III-IV (16.1% vs. 4.1%; HR 4.99, p = 0.012) aGVHD than patients with IPV ≤ 75th percentile. Multivariate analyses showed that high Tac IPV (>50th percentile) was an independent risk factor for grades II-IV (HR 2.99, p = 0.018) and grades III-IV (HR 9.12, p = 0.047) aGVHD. Determination of Tac IPV soon after alloHSCT could be useful in identifying patients at greater risk of aGVHD. [ABSTRACT FROM AUTHOR]