HLA-matched Donor Research Articles

Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Fanconi Anemia: Results of a Single Center with a Fludarabine-Based Conditioning Regimen

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) remains the only curative treatment for bone marrow failure (BMF) and hematologic complications of Fanconi anemia (FA). The evolution remains affected by the toxicity, the risk of graft failure, and clonal evolution. This study aimed to identify factors affecting outcomes in FA patients after allo-HSCT. We included FA patients who underwent allo-HSCT between January 2006 and December 2021. The conditioning regimen was cyclophosphamide/fludarabine (Cy/Flu) ± rabbit anti-thymocyte globulin (ATG). Bone marrow was the stem cell source from HLA-matched related donors in all transplants. Twenty-three patients, 19 with BMF and 4 with MDS/clonal evolution, were included. The median age was 11 years (5-39 years). Five patients (22%) received serotherapy with the conditioning regimen. Engraftment occurred in all patients without severe regimen-related toxicity. The 100-day cumulative incidence (CI) of grade II-IV acute GvHD (a GVHD) and 5-year CI of chronic GvHD (cGVHD) were 17% and 32%, respectively. The 5-year CI of late secondary graft failure was 10.5%. Two patients developed clonal evolution (AML; n = 2) and one patient developed nephrotic syndrome (n = 1). The 10-year overall survival (OS) and event-free survival (EFS) were 80% and 75%, respectively. There was a trend toward a better EFS in patients aged <10 years compared to patients aged ≥10 years (100% versus 61%; p = 0.06). At the last follow-up, 18 patients were alive, and 4 expired. Causes of death were infections with refractory GVHD (n = 1), graft failure (n = 2), and renal failure (n = 1). Despite the small patient population, we show excellent outcomes, particularly for those transplanted in the first decade.

Novel Scoring System for Ranking Hematopoietic Stem Cell Transplantation.

When human leukocyte antigen (HLA)-matched donors are not available for hematopoietic stem cell transplants (HSCT), there are no well-accepted guidelines for ranking 7/8 HLA-matched unrelated donors to achieve optimal transplant outcomes. A novel scoring system for ranking HLA mismatches for these donors was investigated. High-resolution HLA types were used to determine amino acid mismatches located in the HLA antigen-recognition domain. The location and physicochemical properties of mismatched amino acids were used to assign scores for peptide binding, T-cell receptor docking, and HLA structure/function. The scores were tested using a cohort of 2319 patients with leukemia or myelodysplastic syndrome who received their first unrelated donor transplant using conventional graft-versus-host disease (GVHD) prophylaxis between 2000 and 2014. Donors were 7/8 HLA-matched with a single HLA Class I mismatch. Primary outcomes were overall survival and acute GVHD. The scores did not significantly (p<0.01) associate with transplant outcomes, although a Peptide Score = 0 (i.e., no differences in peptide binding; N=146, 6.3%) appears to have lower transplant-related mortality (TRM) compared to higher scores (p=0.019). HLA mismatches with Peptide Score=0 were predominately HLA-C*03:03/03:04 (62%), previously reported to be a permissive mismatch, and a group of 28 other HLA mismatches (38%) that showed similar associations with TRM. This study suggests that HLA mismatches that do not alter peptide binding or orientation (Peptide Score=0) could expand the number of permissive HLA mismatches. Further investigation is needed to confirm this observation and to explore alternative scoring systems for ranking HLA mismatched donors.

Hematopoietic Cell Transplant compared with Standard Care in Adolescents and Young Adults with Sickle Cell Disease

Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2-years after biologic assignment to a Donor or No Donor (SOC) Arm based on the availability of an HLA-matched sibling or unrelated donor (BMTCTN 1503; NCT02766465). A donor search was commenced after eligibility confirmation. The primary endpoint was the comparison of survival 2 years after biologic assignment between treatment arms. Power calculations required 60 participants on the Donor Arm and 140 on the No Donor Arm to determine if early transplant-related mortality might be balanced by disease-related mortality over a longer period of follow-up. Secondary objectives compared changes in SCD-related events, functional outcomes, and organ function. Data were analyzed by the intent-to-treat principle. A total of 113 participants were enrolled, 28 on the Donor and 85 on the No Donor Arm The 2-year probabilities of survival were 89% and 93%, on the Donor and No Donor Arms, respectively. Vaso-occlusive pain (VOC) was less frequent on the Donor Arm in the second year after biologic assignment (p < 0.001). On PROMIS-57 surveys there was decreased fatigue (p=0.003) and an increased ability to participate in social roles and activities (p=0.003) on the Donor Arm 2-years after biologic assignment. Differences in other secondary outcomes did not reach statistical significance. Barriers to accrual prevented an objective comparison of survival. Assignment to the Donor Arm led to improvements in VOC, fatigue, and social function.

Comparison of HLA-haploidentical donors with post-transplant cyclophosphamide versus HLA-matched unrelated donors in peripheral blood stem cell transplantation for acute myeloid leukaemia.

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.

A machine learning-based workflow for predicting transplant outcomes in patients with sickle cell disease.

Allogeneic haematopoietic cell transplantation (HCT) with HLA-matched sibling donor remains the most established curative therapeutic option for patients with sickle cell disease (SCD). However, it is not without risks, highlighting the need for a risk stratification system. Utilizing a machine learning (ML) approach that combines clinical and imaging variables, we identified red cell distribution width and renal organ damage as important risk factors for patients undergoing HCT. This ML-based algorithm, similar to an approach previously reported for predicting mortality in patients with SCD, should be applicable to risk factor discovery in similar studies.

Gene therapy in transfusion-dependent non-β0/β0 genotype β-thalassemia: first real-world experience of beti-cel

AbstractGene addition and editing strategies for transfusion-dependent β-thalassemia have gained momentum as potentially curative treatment options, with studies showcasing their efficacy and safety. We report, to our knowledge, the first real-world application of betibeglogene autotemcel (beti-cel; Zynteglo) during its period of active license in Europe from January 2020 to March 2022 for patients aged ≥12 years without a β0/β0 genotype and without a HLA-matched sibling donor, before beti-cel marketing authorization was withdrawn by its holder because of nonsafety reasons. Among 15 screened patients, 4 opted out for fertility and safety concerns, 2 were excluded because of marked hepatic siderosis, and 1 had apheresis collection failure. Eight patients received beti-cel after busulfan myeloablative conditioning, all achieving transfusion independence within 8 to 59 days, with posttreatment hemoglobin levels ranging from 11.3 to 19.3 g/dL. No deaths occurred, but acute toxicity mirrored busulfan’s known effects. Posttreatment platelet management faced challenges because of HLA-antibodies in 3 patients. Monitoring up to month 24 revealed pituitary-gonadal endocrine dysfunction in all 3 female and in 2 of 5 male patients. Additionally, we observed unexpected posttreatment sequelae: 1 patient developed polycythemia that could not be explained by known genetic or acquired mechanisms, 1 patient developed posttreatment depression and anxiety prohibiting her from returning to work, and 1 patient developed fatigue severely compromising both quality of life and work capacity. This real-world experience corroborates beti-cel’s efficacy and safety and provides information on adverse events observed during real-world use of the therapy.

Comparative outcomes of various transplantation platforms, highlighting haploidentical transplants with post-transplantation cyclophosphamide for adult T-cell leukaemia/lymphoma.

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.

BK virus associated hemorrhagic cystitis in pediatric patients undergoing hematopoietic stem cell transplantation

Abstract Background BK virus (BKV) is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT). Methods Descriptive and retrospective study that included patients from 0-18 years old undergoing HSCT with a diagnosis of HC, admitted from 1/1/2018 to 11/30/2023 in a tertiary care pediatric hospital. Patients with HC were tested for BKV by quantitative polymerase chain reaction (PCR) in urine samples, if positive, plasma viral load was also requested. BKV-HC grading was defined by the European Conference on Infections in Leukemia (ECIL) consensus document. Asymptomatic patients did not undergo standardized screening for BKV. Results During this period 86 HSCT were performed for either malignant (75,6%) or non-malignant disorders (24,4%). Overall, 16 (18,6%) were autologous and 70 (81.4%) were allogeneic: 40 human leukocyte antigen (HLA) matched unrelated donor, 26 HLA-matched related donor and 4 haploidentical. Six patients (7%) suffered HC, all associated with BKV as the cause. These six patients underwent allogeneic HSCT, and 4 of them had HLA-matched unrelated donors. All patients were over 5 years old. Male sex predominated (n:5). All of the patients had hematologic malignancies as the underlying diagnosis (5 with acute lymphoblastic leukemia - ALL). The stem cell source was bone marrow in 3 patients and peripheral blood in the other 3. All patients received myeloablative conditioning regimen and 4 underwent total body irradiation. Only one patient received post-transplant cyclophosphamide. Symptoms (dysuria, abdominal pain, macroscopic hematuria, clots) began more than 14 days after HSCT in 100% of the cases. Hematuria was categorized as grade III in 5 patients and grade IV (severe) only in one. All patients tested positive for BKV PCR in urine samples. High-level BK viruria (&amp;gt;107 copies/mL) was found in 66,6%. BK viremia was detected in 4 patients. All of the patients had another concomitant viral infection, with cytomegalovirus reactivation being the most frequent (n:4). Two patients also had detectable adenovirus (ADV) PCR in urine samples. Acute graft versus host disease (GVHD) was diagnosed in 5 patients, all with skin involvement. All patients were hospitalized and prolonged the length of stay. Regarding treatment, they all received hyperhydration and Cidofovir (more than 3 doses). Dose of immunosuppressive treatment was reduced in 5 cases. Acute kidney failure (AKF) was found in 3 patients. One patient developed chronic kidney failure. The patient with no GVHD was the one who improved the fastest. The patient with severe hematuria required bladder irrigation, had dialysis indication and presented a related death. Conclusion The development of BKV-HC in HSCT patients results in suffering and pain, prolonged hospitalizations and significant morbidity (AKF). Literature shows that male sex, older age and acute GVHD are important risk factors, and this is what we also found in our case series. BKV-HC is considered a difficult and severe condition to manage, remaining troublesome so we should overcome this deficiency with new approaches, particularly emphasizing in preemptive or prophylaxis measures for the benefit of our patients.

Impact of donor type on the outcomes of acute graft versus host disease to systemic corticosteroid therapy.

Systemic corticosteroid therapy is a well-established first-line treatment for grades II-IV acute graft-versus-host disease (aGVHD). Recently, several developments have occurred, including the introduction of transplantation from human leukocyte antigen (HLA) haploidentical donors using post-transplant cyclophosphamide (PTCY-Haplo), and improvements in prognosis after cord blood transplantation (CBT) in Japan. This study aimed to analyze the association between donor sources and outcomes in patients with aGVHD. Our study included 2732 patients who developed grades II-IV aGVHD, and were treated with systemic corticosteroids. We compared HLA-matched related donors (MRD), HLA-matched unrelated donors (MUD), PTCY-Haplo, and CBT. We set endpoint as response rate, 1-year cumulative incidence of non-relapse mortality (NRM), and overall survival (OS). The adjusted odds ratios for a complete response (CR) were 0.99 (95% confidence interval [CI]: 0.74-1.31, P = 0.925) for MUD, 2.08 (95% CI: 1.35-3.25, P = 0.001) for PTCY-Haplo, and 1.08 (95% CI: 0.83-1.41, P = 0.550) for CBT compared with MRD. A significant increase in response rates for PTCY were only found in a single-organ involvement. No significant association was observed between the donor source and NRM or OS. In conclusion, PTCY-Haplo is associated with a high response rate in patients with a single-organ aGVHD; however, MUD and CBT were not associated with treatment response.

Access to Allogeneic Cell Transplantation Based on Donor Search Prognosis: An Interventional Trial.

Patients requiring allogeneic hematopoietic cell transplantation have variable likelihoods of identifying an 8/8 HLA-matched unrelated donor. A Search Prognosis calculator can estimate the likelihood. To determine if using a search algorithm based on donor search prognosis can result in similar incidence of transplant between patients Very Likely (>90%) vs Very Unlikely (<10%) to have a matched unrelated donor. This interventional trial utilized a Search Prognosis-based biologic assignment algorithm to guide donor selection. Trial enrollment from June 13, 2019-May 13, 2022; analysis of data as of September 7, 2023 with median follow-up post-evaluability of 14.5 months. National multi-center Blood and Marrow Transplantation Clinical Trials Network 1702 study of US participating transplant centers. Acute myeloid and lymphoid leukemias, myelodysplastic syndrome, Hodgkin's and non-Hodgkin's lymphomas, severe aplastic anemia, and sickle cell disease patients referred to participating transplant centers were invited to participate. 2225 patients were enrolled and 1751 were declared evaluable for this study. Patients were declared evaluable once it was determined no suitable HLA-matched related donor was available. Patients assigned to the Very Likely arm were to proceed with matched unrelated donor, while Very Unlikely were to utilize alternative donors. A third stratum, Less Likely (∼25%) to find a matched unrelated donor, were observed under standard center practices, but were not part of the primary objective. Cumulative incidence of transplantation by Search Prognosis arm. Evaluable patients included 1751 of which 413 (24%) were from racial/ethnic minorities. Search prognosis was 958 (55%) Very Likely, 517 (30%) Less Likely and 276 (16%) Very Unlikely. 1171 (67%) received HCT, 384 (22%) died without HCT, and 196 (11%) remained alive without HCT. Among the 1,234 patients, the adjusted cumulative incidence (95% CI) of HCT at 6-months was 59.8% (56.7-62.8) in the Very Likely group versus 52.3% (46.1-58.5) in the Very Unlikely (P=0.113). A prospective Search Prognosis-based algorithm can be effectively implemented in a national multicenter clinical trial. This approach resulted in rapid alternative donor identification and comparable rates of HCT in patients Very Likely and Very Unlikely to find a matched unrelated donor. Trial Registration: NCT#03904134.

Establishing the relationship between an adopted recipient and their HLA-matched related donor

Establishing the relationship between an adopted recipient and their HLA-matched related donor

De novo production of granulocyte-macrophage colony-stimulating factor antibodies following hematopoietic stem cell transplantation from HLA-matched unrelated donors is associated with acute graft-versus-host disease

De novo production of granulocyte-macrophage colony-stimulating factor antibodies following hematopoietic stem cell transplantation from HLA-matched unrelated donors is associated with acute graft-versus-host disease

Immunopathology of Corneal Allograft Rejection and Donor-Specific Antibodies (DSAs) as Immunological Predictors of Corneal Transplant Failure.

Despite tremendous developments in the field of laboratory testing in transplantation, the rules of eligibility for corneal transplantation still do not include typing of human leukocyte antigens (HLAs) in the donor and recipient or detection of donor-specific antibodies (DSAs) in the patient. The standard use of diagnostic algorithms is due to the cornea belonging to immunologically privileged tissues, which usually determines the success of transplantation of this tissue. A medical problem is posed by patients at high risk of transplant rejection, in whom the immune privilege of the eye is abolished and the risk of transplant failure increases. Critical to the success of transplantation in patients at high risk of corneal rejection may be the selection of an HLA-matched donor and recipient, and the detection of existing and/or de novo emerging DSAs in the patient. Incorporating the assessment of these parameters into routine diagnostics may contribute to establishing immune risk stratification for transplant rejection and effective personalized therapy for patients.

Sustained HIV remission after allogeneic hematopoietic stem cell transplantation with wild-type CCR5 donor cells.

HIV cure has been reported for five individuals who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with cells from CCR5Δ32 homozygous donors. By contrast, viral rebound has occurred in other people living with HIV who interrupted antiretroviral treatment after undergoing allo-HSCT, with cells mostly from wild-type CCR5 donors. Here we report the case of a male individual who has achieved durable HIV remission following allo-HSCT with cells from an unrelated HLA-matched (9 of 10 matching for HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 alleles) wild-type CCR5 donor to treat an extramedullary myeloid tumor. To date, plasma viral load has remained undetectable for 32 months after the interruption of antiretroviral treatment. Treatment with ruxolitinib has been maintained during this period to treat chronic graft-versus-host disease. Low levels of proviral DNA were detected sporadically after allo-HSCT, including defective but not intact HIV DNA. No virus could be amplified in cultures of CD4+ T cells obtained after antiretroviral treatment interruption, while CD4+ T cells remained susceptible to HIV-1 infection in vitro. Declines in HIV antibodies and undetectable HIV-specific T cell responses further corroborate the absence of viral rebound after antiretroviral treatment interruption. These results suggest that HIV remission could be achieved in the context of allo-HSCT with wild-type CCR5.

Higher survival following transplantation with a mismatched unrelated donor with posttransplant cyclophosphamide-based graft-versus-host disease prophylaxis than with double unit umbilical cord blood in patients with acute myeloid leukemia in first complete remission: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

The best donor option for acute myeloid leukemia (AML) patients lacking an HLA-matched donor has remained intensively debated. We herein report the results of a large retrospective registry study comparing hematopoietic cell transplantation (HCT) outcomes between double-unit umbilical cord blood transplantation (dCBT, n = 209) versus 9/10 HLA-matched unrelated donor (UD) with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis (UD 9/10, n = 270) in patients with AML in first complete remission (CR1). Inclusion criteria consisted of adult patient, AML in CR1 at transplantation, either peripheral blood stem cells (PBSC) from UD 9/10 with PTCy as GVHD prophylaxis or dCBT without PTCy, transplantation between 2013 and 2021, and no in vivo T-cell depletion. The 180-day cumulative incidence of grade II-IV acute GVHD was 29% in UD 9/10 versus 44% in dCBT recipients (p = .001). After adjustment for covariates, dCBT recipients had a higher non-relapse mortality (HR = 2.35, 95% CI: 1.23-4.48; p = .01), comparable relapse incidence (HR = 1.12, 95% CI: 0.67-1.86; p = .66), lower leukemia-free survival (HR = 1.5, 95% CI: 1.01-2.23; p = .047), and lower overall survival (HR = 1.66, 95% CI: 1.08-2.55; p = .02) compared with patients receiving UD 9/10 HCT. In summary, our results suggest that transplantation outcomes are better with UD 9/10 with PTCy-based GVHD prophylaxis than with dCBT for AML patients in CR1. These data might support the use of UD 9/10 with PTCy-based GVHD prophylaxis over dCBT in AML patients lacking an HLA-matched donor.

Impact of “day 90” CD4+ T cells on clinical outcomes in children with relapsed/refractory acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation

BackgroundThe severity of complications after hematopoietic stem cell transplantation (HSCT) is dictated by the degree of immune reconstitution. However, the connection between immune reconstitution and the prognosis of pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. Therefore, the aim of this study was to evaluate the impact of lymphocyte subsets in children diagnosed with refractory or relapsed acute myeloid leukemia (R/R-AML) after allo-HSCT. MethodsWe retrospectively investigated the prognosis and lymphocyte subsets at d 90 (D90) post-allo-HSCT in 130 children diagnosed with R/R-AML between September 2019 and October 2022 at the Children's Hospital of Soochow University. Lymphocyte subgroups were assessed by flow cytometric analysis on D90 and compared among human leukocyte antigen (HLA)-matched sibling donor HSCT (MSD) (n = 14), haploidentical donor HSCT (n = 94), and HLA-matched unrelated donor HSCT (n = 22) groups. The associations between the counts and frequencies of lymphocyte subgroups and prognosis were assessed. ResultsIn the MSD group, CD4+ T cell frequency and count were the highest (P < 0.001). Among the examined lymphocyte subsets, a lower proportion of CD4+ T cells (<14.535 %) at D90 correlated with a higher risk of cytomegalovirus infection (P = 0.002). A higher CD4+ T cell count (>121.39/μL) at D90 after HSCT was the single predictor of a lower fatality risk across all lymphocyte subgroups (univariate: P = 0.038 cut-off: 121.39/μL; multivariate: P = 0.036). No association with relapse was observed. ConclusionsCD4+ T cell count may be used to identify pediatric patients with R/R-AML with a greater mortality risk early after HSCT.

Haploidentical vs HLA-matched sibling donor HCT with PTCy prophylaxis: HLA factors and donor age considerations

AbstractHLA-matched sibling donors (MSDs) are preferred for hematopoietic cell transplantation (HCT). However, the use of alternative donors, especially haploidentical, is increasing, as is our understanding of the impact of HLA factors such as B-leader and DRB1-matching on its outcomes. Yet, data comparing these donor types, particularly considering these HLA factors, is lacking. Herein, we compared haploidentical-HCT (n = 1052) with MSD-HCT (n = 400), both with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease prophylaxis. In multivariate analysis, haploidentical group had similar overall survival (OS; hazard ratio (HR), 0.94; 95% confidence interval [CI], 0.78-1.14; P = .54), nonrelapse mortality (HR, 0.98; 95% CI, 0.72-1.32; P = .87), and relapse (HR, 0.87; 95% CI, 0.70-1.08; P = .20) as the MSD group. Younger donor age was a significant predictor of improved OS. Next, we directly compared the outcomes of “younger” haploidentical (donor age <35 years, n = 347) vs an “older” MSD (donor age ≥50 years, n = 143) in older recipients (patient age ≥50 years). Patients with younger haploidentical B-leader–matched donors had significantly superior OS (HR, 0.65; 95% CI, 0.48-0.90; P = .009) than the older MSD group. Additionally, patients with younger DRB1-mismatched haploidentical donors (HR, 0.63; 95% CI, 0.46-0.87; P = .004) had significantly lower risk of relapse than older MSDs. Our study suggests that haploidentical-HCT may offer comparable outcomes to MSD-PTCy HCT. Moreover, among older patients, a younger haploidentical B-leader–matched donor might be preferable to an older MSD. These findings need validation in larger data sets.

Allogeneic hematopoietic cell transplantation from alternative donors in acute myeloid leukemia.

Allogeneic hematopoietic cell transplantation (HCT) potentially provides a cure for patients with acute myeloid leukemia (AML) who are unlikely to be cured with chemotherapy alone. Previously, human leukocyte antigen (HLA)-matched related donors were used exclusively, which made the procedure available for a limited proportion of patients. The introduction of high-resolution HLA-typing technology, innovations in immunosuppressive therapy, and improved supportive care measures have significantly changed the situation. Now, patients without a matched related donor have an ample opportunity to receive allogeneic HCT with the use of matched or mismatched unrelated donors, umbilical cord blood grafts, or haploidentical related donors. The outcomes of alternative donor transplantations have improved over the past decades, and the growth of unrelated donor registries as well as the donor diversification have enhanced the chance of finding a suitable donor. With multiple alternative donor choices available for most patients, the donor selection is becoming increasingly important. To discuss the optimal donor choice in case of unavailability of an HLA-matched related donor, this article reviews the existing literature of retrospective and prospective comparisons of different alternative donor transplantations in AML and discusses the current state-of-art modalities in allogeneic HCT using alternative donors.

Preliminary Data on SNP of Transplantation-Related Genes after Haploidentical Stem Cell Transplantation.

Background: Hematopoietic stem cell transplantation (HSCT) is one of the mainstream treatments for patients with hematologic malignancies. The matching status of human leukocyte antigen (HLA) between the donor and recipient is highly related to the outcomes of HSCT. Haploidentical HSCT (haplo-HSCT) has emerged as a type of HSCT for patients who cannot find a fully HLA-matched donor. In this study, we investigated whether the single nucleotide polymorphisms (SNPs) of the HLA-related genes and the genes encoding co-stimulatory molecules located on the non-HLA region are related to the outcomes of haplo-HSCT. Methods: The genomic DNAs of 24 patients and their respective donors were isolated from the peripheral blood obtained before performing haplo-HSCT. A total of 75 SNPs of the HLA-related genes (HCP5, NOTCH4, HLA-DOA, LTA, HSPA1L, BAG6, RING1, TRIM27, and HLA-DOB) and the genes located in the non-HLA genes involved in co-stimulatory signaling (CTLA4, TNFSF4, CD28, and PDCD1) were selected to explore their relationship with the outcomes after haplo-HSCT, including graft-versus-host disease, survival status, and relapse. Results: Our data revealed that specific donor or patient SNPs, including rs79327197 of the HLA-DOA gene, rs107822 and rs213210 of the RING1 gene, rs2523676 of the HCP5 gene, rs5742909 of the CTLA4 gene, rs5839828 and rs36084323 of the PDCD1 gene, and rs1234314 of the TNFSF4 gene, were significantly related to the development of adverse outcomes post-haplo-HSCT. Conclusions: These SNPs may play important roles in post-transplant immune response that can be considered during the selection of suitable donors.

Melphalan Dose in Combination With Fludarabine Affects Gastrointestinal Toxicity and Graft-Versus-Host Disease After Allogeneic Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndromes

Fludarabine (Flu) and melphalan (Mel) reduced-intensity conditioning is frequently used for allogenic hematopoietic cell transplant (allo-HCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, there is limited evidence on the impact of Mel dosing on toxicities and clinical outcomes of allo-HCT. We retrospectively compared 8/8 HLA-matched donor allo-HCT outcomes of 345 patients with AML or MDS receiving total Mel dose of 100 mg/m2 (Mel-100, n = 62) versus 140 mg/m2 (Mel-140, n = 283) in combination with Flu. Median age at allo-HCT was 66 years and median follow-up was 36.5 months. For Mel-100 versus Mel-140 groups, any grade gastrointestinal (GI) toxicity rates were 40.3% versus 67.8% (P < .001), day 100 grade II to IV acute graft-versus-host disease (GVHD) rates were 21.0% versus 43.1% (P = .001) and 2-year chronic GVHD rates were 17.4% versus 27.1% (P = .033). In multivariable analysis, Mel-140 resulted in higher risks of GI toxicity (HR = 1.83, P = .013), grade II to IV acute GVHD (HR=2.35, P = .003), and moderate/severe chronic GVHD (HR = 3.13, P = .007). Total Mel dose had no independent impact on oral mucositis, nonrelapse mortality, relapse, relapse-free survival, and overall survival. While independent validation of our observation is warranted, our findings support using Mel-100 in combination with Flu to minimize allo-HCT toxicities and morbidities related to GVHD.