[Pathogenesis and novel therapies for chronic GVHD].

Treatment for chronic graft-versus-host disease, the most important long-term complication of allogeneic hematopoietic cell transplantation, has changed significantly over the past decade. Development of novel targeted therapies has advanced as objective criteria for the diagnosis and evaluation of chronic GVHD have been established and understanding of the biological pathways to pathogenesis has increased. This paradigm shift is driving chronic GVHD practice significantly toward individualized therapy while minimizing exposure to steroids. Treatment using a variety of novel agents, tailored to each individual patient's condition, is expected to improve quality of life and overall survival by preventing chronic GVHD, controlling disease progression, and maintaining motor and occupational functions. This article reviews the pathogenesis of chronic GVHD and discusses prospects for the treatment of chronic GVHD, along with recently approved drugs and promising drugs in development.

Dynamic findings of brain magnetic resonance imaging in a haploidentical hematopoietic stem cell transplantation recipient with cytomegalovirus ventriculoencephalitis: a case report and systematic review.

Our case demonstrated unique cytomegalovirus (CMV) encephalitis post-haploidentical donor hematopoietic stem cell transplantation (HID-HSCT), with early findings on diffusion-weighted brain magnetic resonance imaging (MRI) in the absence of any neurologic symptoms. A 54-year-old Chinese man with acute lymphoblastic leukemia (Philadelphia chromosome-negative) underwent HID-HSCT. After HSCT, the patient developed CMV viremia and severe acute graft-versus-host disease. Recurrence of CMV viremia was observed. On day 129, brain MRI was performed to determine the cause for the intermittent fever. Diffusion-weighted imaging (DWI) revealed several bright spots in the cortex of the frontal lobes and anterior angle of the left lateral ventricle. Subsequently, he developed transplant-associated thrombotic microangiopathy, posterior reversible encephalopathy syndrome, and enlargement of lesions alongside the ventricular wall on a brain MRI series. Metagenomic next-generation sequencing (NGS) of the cerebrospinal fluid (CSF) led to the final diagnosis of CMV encephalitis. Although ganciclovir combined with foscarnet was administered, the patient's consciousness deteriorated, followed by respiratory failure. The patient died on day 198. Additionally, we performed a systematic review to comprehensively analyze this disease. Regarding treatment, immunological therapies, including virus-specific T cells from a third donor and CMV-cytotoxic T lymphocytes, may be more effective. This case report and systematic review underscores the complexities of managing CMV ventriculoencephalitis in HSCT recipients and emphasizes the importance of early diagnosis by brain MRI and CSF polymerase chain reaction or NGS and ongoing research in improving outcomes.

Oral Chronic Graft-versus-Host Disease and Oral Health after Allogeneic Hematopoietic Cell Transplantation - What the Care Team Needs to Know.

Oral chronic graft-versus-host disease (cGVHD) can present with a multitude of clinical signs and is associated with morbidity and lower quality of life. Oral cGVHC may affect the oral mucosa (reticular white striae, erythema, and/or ulcerations), the salivary glands (hyposalivation and/or xerostomia) and the peri-oral soft tissues (fibrosis and trismus). This review provides a practical and concise approach to the diagnosis and management of oral health needs in pediatric and adult alloHCT recipients within the first 2 years post-transplantation.

Cutaneous Chronic Graft-Versus-Host Disease: Clinical Manifestations, Diagnosis, Management, and Supportive Care.

Cutaneous chronic graft-versus-host disease (cGVHD) is associated with morbidity, mortality, and impaired quality of life after hematopoietic stem cell transplantation. The clinical features of cutaneous cGVHD are heterogeneous but can be broadly classified into nonsclerotic or sclerotic presentations. This review provides an overview of clinical presentation, diagnosis and differential diagnosis, grading, and treatment of cutaneous cGVHD. Particular attention is given to cutaneous cGVHD in skin of color, which can have unique features and is generally underrepresented in the literature leading to delays in diagnosis. Finally, an overview of long-term skin care for patients with cutaneous cGVHD is provided in order to support patients from a dermatologic perspective as they recover from cGVHD. Multidisciplinary care with frequent communication between transplant specialists and dermatologists is critical to effectively managing cutaneous cGVHD.

Allogeneic transplantation for adult T-cell leukemia/lymphoma in adolescent and young adults and young patients: A nationwide retrospective study by the ATL working group of the Japan society for transplantation and cellular therapy.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides durable remission for patients with adult T-cell leukemia/lymphoma (ATL); however, few studies have focused on post-transplant outcomes in ATL patients ≤49 years. To clarify prognostic factors in ATL among patients <40 years (adolescents and young adult [AYA]; n = 73) and 40-49 years (Young; n = 330), we conducted a nationwide retrospective study. Estimated 3-year overall survival (OS) rates were 61.8% and 43.1% in AYA and Young patients, respectively (p = 0.005). In the multivariate analysis, Young patients showed worse OS (Hazard ratio (HR) [95% confidential interval] 1.62 [1.10-2.39], p = 0.015), chronic graft-versus-host disease (GVHD)-free and relapse-free survival (CRFS) (HR 1.54 [1.10-2.14], p = 0.011), and GVHD-free and relapse-free survival (GRFS) (HR 1.40 [1.04-1.88], p = 0.026) than AYA patients. No significant differences were observed in OS, CRFS, or GRFS between the myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) regimens; however, non-relapse mortality was significantly lower in patients with the RIC regimen than those with the MAC regimen (HR 0.46 [0.24-0.86], p = 0.015). In summary, OS was worse in Young patients than in AYA patients in the allo-HSCT setting for ATL. Furthermore, the RIC regimen has potential as an alternative treatment option for ATL patients ≤49 years.

Grading Histopathology Features of Graft-versus-host Disease in Animal Models; A Systematic Review.

Graft-versus-host disease (GvHD), a frequent and severe complication following allogeneic hematopoietic stem cell transplantation, presents substantial morbidity and mortality risks. The crucial role of histopathological examination in diagnosing and grading GvHD, particularly within animal models, is pivotal for elucidating disease mechanisms and assessing emerging therapies. This systematic review aims to critically evaluate the various grading systems for GvHD in animal models, emphasizing histopathological characteristics. In this endeavor, we meticulously examined original research articles sourced from PubMed, Scopus, Web of Science, and Google Scholar. Our findings reveal a diverse array of grading systems, each differing in the tissues examined, criteria evaluated, severity scoring scales, and the granularity of the information provided. Predominantly, skin, liver, and gut tissues are assessed, though some systems also incorporate lung and thymus evaluations. This review will delve into the alignment between clinical and histological grading in animal models of GvHD, also casting light on prospective advancements and the impact of technological progress. In conclusion, our analysis underscores the imperative need for uniform criteria and consistent application of grading systems. Such standardization is essential to foster comparability across studies and enhance the translation of preclinical discoveries into clinical applications.

Oral Chronic Graft-Versus-Host Disease: Pathogenesis, Diagnosis, Current Treatment, and Emerging Therapies.

Chronic graft-versus-host disease (cGvHD) is a multisystem disorder that occurs in recipients of allogeneic hematopoietic (alloHCT) stem cell transplants and is characterized by both inflammatory and fibrotic manifestations. It begins with the recognition of host tissues by the non-self (allogeneic) graft and progresses to tissue inflammation, organ dysfunction and fibrosis throughout the body. Oral cavity manifestations of cGVHD include mucosal features, salivary gland dysfunction and fibrosis. This review synthesizes current knowledge on the pathogenesis, diagnosis and management of oral cGVHD, with a focus on emerging trends and novel therapeutics. Data from various clinical studies and expert consensus are integrated to provide a comprehensive overview.

Umbilical cord blood stem cells as third-party adjuvant infusions in human leukocyte antigen antibody-positive patients undergoing haploidentical hematopoietic stem cell transplantation.

Introduction: Graft failure (GF) or poor graft function (PGF) remain critical obstacles in haploidentical hematopoietic stem cell transplantation (haplo-HSCT), especially in recipients with HLA antibodies. Here, we performed a retrospective cohort study to investigate the efficacy and safety of the use of unrelated umbilical cord blood stem cells (UCBs) as a third-party adjuvant infusion in patients with HLA-antibodies undergoing haplo-HSCT. Methods: A total of 90 patients were divided into three groups: 17 patients in Group A (with positive HLA antibodies and who received UCB infusion), 36 patients in Group B (with positive HLA antibodies without UCB infusion), and 37 patients in Group C (without HLA antibody or UCB infusion). Results: The median age of patients included in Groups A, B, and C was 43 (IQR, 27 - 49.5), 33 (IQR, 20 - 48.75), and 30 (IQR, 18 - 46.5) years, respectively. All but one patient in Group B achieved granulocyte recovery within 28 days after transplantation. The median time to granulocyte engraftment were all 12 days for patients in Groups A, B, and C, respectively. All the patients in Group A achieved 100% donor chimerism without UCB engraftment. There were no significant differences in granulocyte or platelet engraftment time between the three groups. There were 1, 5, and 0 patients in Groups A, B, and C, respectively, who developed PGF. The cumulative incidence rates for any grade of acute graft-versus-host disease (aGVHD) were comparable among the three groups. Patients in Group B presented a greater incidence of cGVHD than did those in Group A (P = 0.002) and Group C (P = 0.006). Patients in Group A presented more limited and milder cGVHD than those in Group C (P < 0.0001). The 1-year relapse-free survival (RFS) was 70.6% (95% CI, 0.47 - 0.87), 55.6% (95% CI, 0.40 - 0.70), and 77.9% (95% CI, 0.63 - 0.89) in Groups A, B, and C, respectively. Discussion: Our results indicated that patients who were positive for HLA antibodies were at a greater risk of developing GF/PGF. Co-infusion with UCBs was safe and improved engraftment, cGVHD, and improved the 1-year RFS to some extent.

Monocytes as an early risk factor for acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and contributes to high morbidity and mortality. However, our current understanding of the development and progression of aGVHD after allo-HSCT remains limited. To identify the potential biomarkers for the prevention and treatment of aGVHD during the early hematopoietic reconstruction after transplantation, we meticulously performed a comparative analysis of single-cell RNA sequencing data from post-transplant patients with or without aGVHD. Prior to the onset of aGVHD, monocytes in the peripheral blood of patients with aGVHD experienced a dramatic rise and activation on day 21 post-transplantation. This phenomenon is closely aligned with clinical cohort results obtained from blood routine examinations. Furthermore, in vitro co-culture experiments showed that peripheral blood monocytes extracted from patients with aGVHD approximately 21 days post-transplantation induced a significantly higher proliferation rate of allogeneic T cells compared to those from patients without aGVHD. Our study indicates that monocytes could be a crucial early clinical risk factor for the development of aGVHD, and this insight could potentially guide the timing of monitoring efforts, recommending assessments at the pivotal juncture of approximately day 21 post-transplantation, shedding fresh light on the significance of early hematopoietic regeneration in relation to the onset of aGVHD.

Comparison of hematopoietic stem cell transplantation and repeated intensified immunosuppressive therapy as second-line treatment for relapsed/refractory severe aplastic anemia.

The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.

Successful Haematopoietic Stem Cell Transplantation for LRBA Deficiency with Fludarabine, Treosulfan, and Thiotepa-Based Conditioning.

LRBA deficiency is an inborn error of immunity defined by autoimmunity, lymphoproliferation, recurrent infections, cytopenia, and inflammatory bowel disease. Despite recent advances in managing this disease with targeted biologic therapy, haematopoietic stem cell transplant (HSCT) remains the only cure. However, great variability exists between protocols used to transplant patients with LRBA deficiency. We describe a cohort of seven patients with LRBA deficiency who underwent HSCT using a myeloablative, reduced toxicity regime of fludarabine, treosulfan, and thiotepa at two transplantation centres from 2016 to 2019. Data were collected both retrospectively and prospectively, measuring time to engraftment, infectious complications, incidence of graft versus host disease, and post-transplantation chimerism. Six of seven patients survived transplantation, and four of six surviving patients achieving treatment-free survival. We thus recommend that HSCT with fludarabine, treosulfan, and thiotepa-based conditioning be considered in patients with LRBA deficiency.

Comparison of Cytomegalovirus Reactivation in Children After Allogeneic Hematopoietic Cell Transplantation in 2 Transplant Eras.

BACKGROUND: Reactivation of cytomegalovirus (CMV) is typically considered harmless as long as the immune system remains unaffected by medications or other factors. CMV reactivation may occur as a result of acute graft-versus-host disease of Grades II to IV. One possible factor contributing to this risk is the rise in the number of donors who lack genetic similarities or relationships. We hypothesized that the anti-CMV IgG level before transplantation could potentially serve as an indicator of the likelihood of CMV reactivation following hematopoietic cell transplantation. METHODS: We examined a cohort of young individuals who underwent allogeneic HCT between 1998 and 2022 to evaluate the occurrence of CMV reactivation. The patients were divided into 2 time periods: 1998 to 2016 (comparison group) and 2017 to 2022 (intervention group). RESULTS: Between 1998 and 2016, 292 patients underwent hematopoietic HCT. Recipients from 2017 to 2022 experienced a slightly higher risk of CMV reactivation than those from 1998 to 2016. The comparison of prophylactic and preemptive medication showed no significant difference between the periods (P = .32). Patients treated from 1998 to 2016 experienced a 23% decrease in the risk of symptomatic CMV reactivation and related illnesses compared to those treated from 2017 to 2022 (P = .08 and .15, respectively). CONCLUSIONS: Our study showed that the intervention group had more symptomatic CMV reactivations. Various factors may contribute to this, including CD19-directed immunotherapy and the CMV status of the recipient before transplantation.

Human leukocyte antigen evolutionary divergence as a novel risk factor for donor selection in acute lymphoblastic leukemia patients undergoing haploidentical hematopoietic stem cell transplantation.

Introduction: The human leukocyte antigen (HLA) evolutionary divergence (HED) reflects immunopeptidome diversity and has been shown to predict the response of tumors to immunotherapy. Its impact on allogeneic hematopoietic stem cell transplantation (HSCT) is controversial in different studies. Methods: In this study, we retrospectively analyzed the clinical impact of class I and II HED in 225 acute lymphoblastic leukemia patients undergoing HSCT from related haploidentical donors. The HED for recipient, donor, and donor-recipient pair was calculated based on Grantham distance, which accounts for variations in the composition, polarity, and volume of each amino acid within the peptide-binding groove of two HLA alleles. The median value of HED scores was used as a cut-off to stratify patients with high or low HED. Results: The class I HED for recipient (R_HEDclass I) showed the strongest association with cumulative incidence of relapse (12.2 vs. 25.0%, P = 0.00814) but not with acute graft-versus-host disease. The patients with high class II HED for donor-recipient (D/R_HEDclass II) showed a significantly higher cumulative incidence of severe aGVHD than those with low D/R_HEDclass II (24.0% vs. 6.1%, P = 0.0027). Multivariate analysis indicated that a high D/R_HEDclass II was an independent risk factor for the development of severe aGVHD (P = 0.007), and a high R_HEDclass I had a more than two-fold reduced risk of relapse (P = 0.028). However, there was no discernible difference in overall survival (OS) or disease-free survival (DFS) for patients with high or low HED, which was inconsistent with the previous investigation. Discussion: While the observation are limited by the presented single center retrospective cohort, the results show that HED has poor prognostic value in OS or DFS, as well as the associations with relapse and aGVHD. In haploidentical setting, class II HED for donor-recipient pair (D/R_HEDclass II) is an independent and novel risk factor for finding the best haploidentical donor, which could potentially influence clinical practice if verified in larger cohorts.

Anti-PD-1 combined with hypomethylating agent and CAG regimen bridging to allogeneic hematopoietic stem cell transplantation: a novel strategy for relapsed/refractory acute myeloid leukemia.

Introduction: The prognosis of relapsed/refractory acute myeloid leukemia (r/rAML) is dismal, and allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potential cure. Combining anti-PD-1, hypomethylating agent (HMA), and CAG (cytarabine, aclarubicin/idarubicin, granulocyte colony-stimulating factor) regimen has showed primary efficacy in r/rAML. However, pre-transplant exposure to anti-PD-1 may lead to severe graft-versus-host disease (GVHD). This preliminary study aimed to evaluate the safety and efficacy of allo-HSCT in r/rAML patients receiving the anti-PD-1+HMA+CAG regimen. Methods: Fifteen r/rAML patients (12 related haploidentical donors [HIDs], 2 matched siblings, 1 unrelated donor) received this regimen and subsequent peripheral blood HSCT. Results: Four patients with HIDs received a GVHD prophylaxis regimen consisted of Anti-thymocyte globulin and a reduced-dose of post-transplant cyclophosphamide. The median follow-up was 20.9 months (range, 1.2-34.2). The cumulative incidences of acute GVHD grade 2-4 and grade 3-4 were 40% and 13.3%, respectively. The 2-year incidence of moderate-to-severe chronic GVHD, non-relapse mortality, and relapse were 10%, 22.3%, and 22.5%, respectively. The 2-year overall survival and GVHD-free/relapse-free survival rates were 54% and 48.6%, respectively. No death or relapse was observed in the PTCy group. Conclusion: The anti-PD-1+HMA+CAG regimen bridging to allo-HSCT for r/r AML was tolerable with promising efficacy. GVHD prophylaxis with PTCy for HID-HSCT showed preliminary survival advantage.

[Chinese consensus on autologous stem cell transplantation for adult acute leukemia (2024)].

Autologous stem cell transplantation (ASCT) emerges as a therapeutic strategy following remission in adult acute leukemia (AL). It offers advantages over allogeneic hematopoietic stem cell transplantation (allo-HSCT), including independence from donor availability, absence of graft-versus-host disease (GVHD), and a reduced risk of transplant-related mortality. Furthermore, when juxtaposed with the extended regimens of consolidation chemotherapy, ASCT stands out by markedly abbreviating treatment duration, alleviating the economic strain on patients, and enhancing their overall quality of life. Despite these benefits, the adoption of ASCT among adult AL patients in China remains disproportionately low. To enhance clinical physicians' understanding of the role and position of ASCT in AL management and to improve the clinical efficacy of ASCT, it is urgent to establish a consensus among experts on ASCT for adult acute leukemia in our nation.

TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL.

The aim of this retrospective study was to evaluate the efficiency and safety of total body irradiation plus cyclophosphamide (TBI/Cy) followed by autogenetic hematopoietic stem cell transplantation (auto-HSCT) in T-LBL/ALL patients that cannot receive allogeneic hematopoietic stem cell transplant (allo-HSCT). Between 2013 and 2023, 24 patients received auto-HSCT following by TBI/Cy, 26 patients underwent allo-HSCT, all patients achieved completed hematopoietic reconstitution after HSCT. The progression free survival (PFS) and overall survival (OS) had no statistically significant differences between the two groups (P = 0.791, HR 1.127, 95%CI 0.456-2.785; P = 0.456, HR 0.685, 95%CI 0.256-1.828). Although the cumulative incidence of relapse was lower for patients who received allo-HSCT than auto-HSCT (P = 0.033, HR 3.707, 95%CI 1.188-11.570, 2-year relapse 11.5% vs. 33.3%), the incidence of non-relapse mortality (NRM) was higher than that in the auto-HSCT group (P = 0.014, HR 0.000, 95%CI -1.000 - -1.000, 2-year NRM, 23.1% vs. 0%). Trough Landmark analysis, the two groups showed a statistically significant difference in 3-year PFS and 4-year OS curves (Figure S2A&B, P = 0.039, HR 0.426, 95%CI 0.163-1.117; P = 0.014, HR 0.317, 95%CI 0.113-0.887). By COX analysis, poor baseline performance status (ECOG-PS ≥ 2) and CNS involvement were risk factors for PFS and OS. In conclusion, TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL.

ATG-Thymoglobulin Versus ATG-Fresenius for Conditioning in Thalassemia Patients Who Underwent Allogenic Stem Cell Transplantation from Matched-Sibling Donor: A Tertiary Cancer Care Center Short-Term Experience.

Graft rejection and Graft-versus-host disease (GVHD) are some of the significant factors resulting in morbidity and mortality following allogeneic hematopoietic cell transplantation. Prophylaxis for GVHD using T-cell depleting agents is helpful in reducing the transplant-related mortality and graft rejection. Both tATG and fATG exhibit varied amounts of antibody specificities and perform distinct immunomodulatory effects, regardless of their capacity to deplete T-lymphocytes. We conducted this single-center, retrospective study at our center to compare both formulations. Twenty-six patients were included in the study, 13 in each cohort. The median age at diagnosis of ß-thalassemia was 5 months (range, 3-12 months) in the tATG group and 6 months (range, 3-9 months) in the f-ATG group, respectively. Acute GVHD was observed in 1 (7.7) and 2(15.4) in the tATG and fATG group, respectively. No cases of chronic GVHD were observed in either group. There was no difference in the mixed chimerism observed at 6 months in both groups, tATG (n = 5, 38.5%) and fATG (n = 6, 46.15). There was 1 (7.6) rejection at day +72 observed in the tATG group, whereas no rejection was observed in the fATG group. At a mean follow-up duration of 288 days since transplant, there were no deaths in either of the groups. In conclusion, both ATG preparations showed equivalent effectiveness in preventing rejections and GVHD. However, further larger studies are required to establish the long-term efficacy and safety of both formulations in ASCT.

Impaired survival of patients with non donor-specific anti-HLA antibodies before HLA-mismatched allogeneic stem cell transplantation.

BACKGROUND: While the detrimental role of donor-specific anti-HLA antibodies (DSAs) is well-described in the setting of hematopoietic stem cell transplantation (HSCT), few studies focus on non donor-specific ones and with controversial results. METHODS: We here report our monocenter experience on 64 adult patients receiving allogeneic HSCT from a HLA-mismatched donor between 2014 and 2022 who were tested for the presence of anti-HLA antibodies before transplant, focusing on fifteen patients with non donor-specific anti-HLA antibodies. RESULTS: The survival of patients with non donor-specific anti-HLA antibodies was inferior with respect to patients without anti-HLA antibodies and similar to patients with DSAs. Median survival of patients with non donor-specific anti-HLA antibodies was 21 months (95 % CI: 9-42) vs. 61 months (95 % CI: 17-77) among the anti-HLA antibody-negative patients, with a significantly higher mortality incidence rate ratio (3.3 times-fold greater, p = 0.01). No pattern of death causes was found CONCLUSIONS: In this monocenter series of HLA-mismatched HSCTs, impaired survival was observed in adult patients having non donor-specific anti-HLA antibodies before transplant, similar to those with DSAs. Our findings support those antibodies as a negative predictive factor even if they are not directed against the donor, thus warranting further investigation on larger cohorts.

[Selected donor CD34(+) cell boosts for salvage treatment of poor graft function following allogeneic hematopoietic stem cell transplantation in primary myelofibrosis: 3 cases report].

A retrospective analysis was conducted on three patients with primary myelofibrosis who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from 2020 to 2023. They subsequently developed poor graft function. The patients received selected donor CD34(+) cell boosts as salvage therapy. There were two male patients and one female patient, with a median age of 68 (39-69) years. The median time from allo-HSCT to the selected donor CD34(+) cell boost was 83 (56-154) days. The median infusion of selected donor CD34(+) cells was 7.67 (7.61-9.06) ×10(6)/kg, with a CD34(+) cell purity of 97.76% (96.50%-97.91%) and a recovery rate of 70% (42%-75%) . Hematological recovery was achieved in two cases. No acute GVHD was observed in any of the three patients. One case of moderate oral chronic GVHD was noted. Selected donor CD34(+) cell boosts for the treatment of poor graft function after allo-HSCT in primary myelofibrosis was effective and no severe acute or chronic GVHD was observed.