Mini-dose methotrexate combined with methylprednisolone for the initial treatment of acute GVHD: a multicentre, randomized trial.

BACKGROUND: There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. RESULTS: The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups. CONCLUSIONS: In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. TRIAL REGISTRATION: The trial was registered with clinicaltrials.gov (NCT04960644).

Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial).

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

Comparable long-term outcomes between upfront haploidentical and identical sibling donor transplant in aplastic anemia: a national registry-based study.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curative option for severe aplastic anemia (SAA), and transplantation from identical sibling donors (ISD) has been recommended as a first-line treatment. Haploidentical donor (HID) transplantation for SAA has made great advances; thus, an increased role of HID-SCT in SAA should be considered. We performed a national registry-based analysis comparing long-term outcomes in the upfront HID or upfront ISD SCT setting. A total of 342 SAA patients were enrolled, with 183 patients receiving HID SCT and 159 receiving ISD SCT. The estimated 9-year overall survival and failure-free survival were 87.1±2.5% and 89.3±3.7% (P=0.173) and 86.5±2.6% versus 88.1±3.8% (P=0.257) for patients in the HID and ISD SCT groups, respectively. Transplantation from HID or ISD SCT has greatly improved quality of life (QoL) levels post-HSCT compared to pre-HSCT. The occurrence of chronic graft-versus-host disease was the only identified adverse factor affecting each subscale of QoL. Physical and mental component summaries in adults as well as physical, mental, social, and role well-being in children were all similar between HID and ISD SCT at 5-year time points. At the last follow-up, the proportion of returning to society was comparable between the HID and ISD groups, showing 78.0% versus 84.6% among children and 74.6% versus 81.2% among adults. These data suggest that haploidentical transplant can be considered a potential therapeutic option in the upfront setting for SAA patients in the absence of an HLA-identical related or unrelated donor.

Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

Ponatinib therapy in recurrent Philadelphia chromosome-positive central nervous system leukemia with T315I mutation after Allo-HSCT.

Central nervous system leukemia (CNSL) relapse is relatively common among Philadelphia chromosome-positive (Ph+) leukemia patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). The prognosis of patients is dismal for those with a BCR-ABL T315I mutation, which is resistant to TKIs including second-generation drugs. We assessed ponatinib for nine patients with recurrent Ph+ CNSL and a T315I mutation after allo-HSCT, including five patients with Ph+ acute lymphoblastic leukemia and four with chronic myelogenous leukemia. Five patients experienced isolated CNSL relapse, and four experienced CNSL with hematologic relapse. All patients received ponatinib combined with intrathecal chemotherapy, and four patients with hematologic relapse received systemic chemotherapy and/or donor lymphocyte infusion. All patients achieved a deep molecular response and central nervous system remission (CNSR) at a median time of 1.5 (range: 0.7-3) months after ponatinib treatment. Two patients experienced a second CNSL relapse due to ponatinib reduction, but they achieved CNSR again after an increase to the standard dosage. Six patients developed graft versus host disease. By April 1, 2019, eight patients were alive, and one died of pneumonia. The median time of survival after the first CNSL relapse posttransplantation was 18 (range: 11.2-48.5) months. Our data from a small number of samples suggests that ponatinib is effective for recurrent Ph+ CNSL patients with a BCR-ABL T315I mutation after allo-HSCT and warrants broader clinical evaluation.

Improved survival after offspring donor transplant compared with older aged-matched siblings for older leukaemia patients.

Donor selection for older leukaemia patients undergoing haematopoietic cell transplant (HCT) is not well defined: outcomes might be improved with a younger offspring donor rather than an older human leukocyte antigen (HLA)-matched sibling donor (MSD). We extended our multicentre dataset. A total of 185 acute leukaemia patients (≥ 50 years) transplanted in first complete remission who received HCT from offspring (n = 62) or MSD (n = 123) were included. A 1:1 ratio matched-pair analysis was performed. We were able to match 54 offspring with 54 MSD patients. Outcomes were compared between the two matched-pair groups. The cumulative incidence of grade II/IV acute graft-versus-host disease (GVHD) (26% vs. 35%; P = 0·23) and chronic GVHD (37% vs. 24%; P = 0·19) was comparable between groups (MSD vs. offspring). The lower three-year transplant-related mortality (9% vs. 26%; P = 0·023) and relapse incidence (6% vs. 17%; P = 0·066) resulted in higher overall survival (85% vs. 58%; P = 0·003) and leukaemia-free survival (LFS) (85% vs. 56%; P = 0·001) in offspring HCT compared with that in MSD HCT. These data might favour a young offspring over an older MSD in patients >50 years. The current analyses confirm that non-HLA donor characteristics, such as kinship and donor age, rather than HLA disparity, predominantly influence survival in older acute leukaemia patients.

Prophylactic Donor Lymphocyte Infusion (DLI) Followed by Minimal Residual Disease and Graft-versus-Host Disease-Guided Multiple DLIs Could Improve Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Refractory/Relapsed Acute Leukemia.

Patients with refractory/relapsed acute leukemia who have received allogeneic hematopoietic stem cell transplantation (allo-HSCT) are still at a high risk for relapse post-transplant. To investigate the impact of prophylactic donor lymphocyte infusion (DLI) followed by minimal residual disease (MRD) test and graft-versus-host disease (GVHD)-guided multiple DLIs to prevent relapse and improve survival in patients with refractory/relapsed acute leukemia who received allo-HSCT. A multicenter prospective study was designed. In total, 100 patients who achieved complete remission at 30 days post-transplant and had no uncontrolled infection, organ failure, or active GVHD were eligible First, prophylactic DLI was administered at 30 days after HLA-matched related HSCT or 45 to 60 days after HLA-matched unrelated HSCT or haploidentical HSCT. Subsequently, multiple DLIs were administered based on the results of MRD test and whether they developed GVHD. In addition to DLI, chemotherapy was also given to patients who had a positive MRD test. Three-year cumulative incidence of relapse, leukemia-free survival, and survival post-transplant were 32.4% (95% confidence interval, 22.4% to 42.4%), 50.3% (95% confidence interval, 40.3% to 60.3%), and 51.4% (95% confidence interval, 41.2% to 61.6%), respectively. In multivariate analysis, a positive MRD test (HR, 3.840; 95% confidence interval, 1.678 to 5.784; P= .001) and receiving 1 course of DLI (HR, 4.346; 95% confidence interval, 1.223 to 9.450, P= .023) were associated with an increased relapse risks. These data suggest that prophylactic DLI followed by MRD test and GVHD-guided multiple DLIs reduced relapse and increased survival post-transplant in patients with refractory/relapsed acute leukemia who received allo-HSCT. The study is registered at www.ClinicalTrials.gov as NCT01455272.

Haploidentical transplantation compared with matched sibling and unrelated donor transplantation for adults with standard-risk acute lymphoblastic leukaemia in first complete remission.

We retrospectively investigated outcomes of haploidentical donor (HID) transplant for adults with standard-risk acute lymphoblastic leukaemia (ALL) in first complete remission (CR1) compared with human leucocyte antigen (HLA)-matched sibling donor (MSD) and HLA-matched unrelated donor (MUD) transplants. A total of 348 adult patients were enrolled, including 127 HID, 144 MSD and 77 MUD recipients. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 39·5%, 24·0% and 40·3% for HID, MSD and MUD, respectively (P = 0·020). However, there was no difference in grade III-IV aGVHD (11·4%, 7·7%, 13·5%, respectively, P = 0·468). The 5-year cumulative transplant-related mortality was 16·4%, 11·6% and 19·6% (P = 0·162), the 5-year relapse rate post-transplantation was 14·8%, 21·1% and 16·7% (P = 0·231), the 5-year overall survival was 70·1%, 73·7% and 69·8% (P = 0·525), and the 5-year disease-free survival was 68·7%, 67·3% and 63·7%, respectively (P = 0·606). Furthermore, the 3-year GVHD-free, relapse-free survival was not different (50·8%, 54·9% and 52·2%, respectively, P = 0·847). Our results indicate that the outcomes of HID transplants are equivalent to those of MSD and MUD, and that HID transplantation is a valid alternative for standard-risk adults with ALL in CR1 who lack matched donors.

The Relationship Between MMP-2 -1306C>T and MMP-9 -1562C>T Polymorphisms and the Risk and Prognosis of T-Cell Acute Lymphoblastic Leukemia in a Chinese Population: A Case-Control Study.

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematological disease and is often accompanied by a variety of genetic abnormalities. Hence, our study aims to investigate the relationship between MMP-2 -1306C>T and MMP-9 -1562C>T polymorphisms and the risk and prognosis of T-ALL. METHODS: From April 2009 to February 2011, a total of 376 T-ALL patients were chosen as the case group. Meanwhile, 352 healthy people who passed routine health examinations were selected as the control group. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to detect the frequency of MMP-2 -1306C>T (rs243865) and MMP-9 -1562C>T (rs3918242) polymorphisms in the study subjects. The serum levels of MMP-2 and MMP-9 were detected using enzyme-linked immunosorbent assay (ELISA). A Kaplan-Meier analysis was employed to analyze the event-free survival (EFS) rates of the T-All patients with different MMP-2 and MMP-9 genotypes. A multivariate COX model was applied to analyze the relationship between MMP-2 and MMP-9 polymorphisms and the prognosis of T-ALL patients. A C-statistic and net reclassification index (NRI) was carried out to evaluate the predictive value of MMP-2 and MMP-9 gene polymorphisms using the Cox model. RESULTS: Compared to the control group, the genotypic frequency of MMP-2 -1306C>T (CT + TT) and MMP-9 -1562C>T (CT + TT) in the case group was significantly higher. The serum level of MMP-9 was markedly elevated in T-ALL patients with the CT + TT genotype compared to patients with the CC genotype. The results of the Kaplan-Meier analysis showed that the median EFS was lower in T-ALL patients with the CT + TT genotype of MMP-9 -1562C>T compared to patients with the CC genotype. The results of a multivariate analysis using the Cox proportional hazard model indicated that the MMP-9 -1562C>T polymorphism was associated with the prognosis of T-ALL patients. CONCLUSION: These results indicated that MMP-2 -1306C/T and MMP-9 -1562C/T polymorphisms might be associated with an increased risk of T-ALL. The MMP-9 -1562C>T polymorphism may also be related to the prognosis of T-ALL patients.

Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study.

The effects of HLA-identical sibling donor (ISD) hematopoietic stem cell transplantation (HSCT) on adults with intermediate- or high-risk acute myeloid leukemia (AML) in the first complete remission (CR1) are well established. Previous single-center studies have demonstrated similar survival after unmanipulated haploidentical donor (HID) vs ISD HSCT for hematologic malignancies. To test the hypothesis that haploidentical HSCT would be a valid option as postremission therapy for AML patients in CR1 lacking a matched donor, we designed a disease-specific, prospective, multicenter study. Between July 2010 and November 2013, 450 patients were assigned to undergo HID (231 patients) or ISD HSCT (219 patients) according to donor availability. Among HID and ISD recipients, the 3-year disease-free survival rate was 74% and 78% (P = .34), respectively; the overall survival rate was 79% and 82% (P = .36), respectively; cumulative incidences of relapse were 15% and 15% (P = .98); and those of the nonrelapse-mortality were 13% and 8% (P = .13), respectively. In conclusion, unmanipulated haploidentical HSCT achieves outcomes similar to those of ISD HSCT for AML patients in CR1. Such transplantation was demonstrated to be a valid alternative as postremission treatment of intermediate- or high-risk AML patients in CR1 lacking an identical donor. This trial was registered at www.chictr.org as #ChiCTR-OCH-10000940.

Haplo-identical transplantation for acquired severe aplastic anaemia in a multicentre prospective study.

We conducted a prospective, multicentre study to confirm the feasibility of haplo-identical transplantation in treatment of severe aplastic anaemia (SAA) as salvage therapy, by analysing the outcomes of 101 patients who received haplo-identical transplantation between June 2012 and October 2015. All cases surviving for more than 28 d achieved donor myeloid engraftment. The median time for myeloid engraftment was 12 (range, 9-25) days and 15 (range, 7-101) days for platelets, with a cumulative platelet engraftment incidence of 94·1 ± 0·1%. With a median follow-up of 18·3 (3·0-43·6) months, recipients from haplo-identical transplantation had more cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD, 33·7% vs. 4·2%, P < 0·001), more chronic GVHD (22·4% vs. 6·6%, P = 0·014) at 1 year, but similar grade III-IV aGVHD (7·9% vs. 2·1%, P = 0·157), 3-year estimated overall survival (OS, 89·0% vs. 91·0%, P = 0·555) and failure-free survival (FFS, 86·8% vs. 80·3%, P = 0·659) when compared with 48 patients who received contemporaneous transplantation from matched related donors. Multivariate analysis showed no significant difference in engraftment and survival between the two cohorts. Both OS and FFS for the entire population correlated significantly with grades III-IV aGVHD. In conclusion, haplo-identical transplantation is a feasible choice for SAA with favourable outcomes.

In adults with t(8;21)AML, posttransplant RUNX1/RUNX1T1-based MRD monitoring, rather than c-KIT mutations, allows further risk stratification.

We asked whether minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels could identify allogeneic hematopoietic stem cell transplantation (allo- HSCT) t(8;21) (q22;q22) acute myeloid leukemia patients who are at high risk for relapse, together with the impact of c-KIT mutations. Ninety-two consecutive adult t(8;21) patients who received allo-HSCT in complete remission were enrolled. MRD status at 1, 2, and 3 months after HSCT identified relapse patients (P5.05, P < .001, P5.0001, respectively). The 2-year cumulative incidence of relapse (CIR) and leukemia-free survival (LFS) was 32% vs 9% (P 5 .01) and 55% vs 70% (P 5 .12) for patients with and without c-KIT mutations, respectively. In multivariate analysis, MRD at the first 3 months after HSCT, rather than c-KIT mutations,was an independent factor for CIR (P5.001) and LFS(P5.001). In addition, 17 patients received donor lymphocyte infusion (DLI) as interventional therapy for MRD, and the 2-year CIR and LFS for patients with or without DLI was 24% vs 87% (P5.001) and 64%vs 0%(P < .001), respectively. In conclusion, MRD monitoring early after transplant allows further rapid identification of t(8;21) patients at high risk of relapse and was more predictive of relapse risk than c-KIT mutations.

Mesenchymal stem cells versus mesenchymal stem cells combined with cord blood for engraftment failure after autologous hematopoietic stem cell transplantation: a pilot prospective, open-label, randomized trial.

Engraftment failure (EF) after autologous hematopoietic stem cell transplantation is a serious complication. We prospectively evaluated the effects and safeties of mesenchymal stem cells (MSCs) alone and MSCs combined with cord blood (CB) for EF. Twenty-two patients were randomized to receive MSCs (MSC group; n = 11) or MSCs plus CB (CB group; n = 11). Patients with no response (NR) to MSCs received the therapeutic schedule in the CB group, and those patients with partial response (PR) in the MSC group and patients without complete remission (CR) in the CB group received another cycle of MSC treatment. Patients who did not achieve CR after 2 cycles of treatments received other treatments, including allogeneic HSCT. After the first treatment cycle, response was seen in 7 of 11 patients in the MSC group and in 9 of 11 in the CB group (P = .635), with a significant difference in neutrophil reconstruction between the 2 groups (P = .030). After 2 treatment cycles, 16 patients achieved CR, 3 achieved PR, and 3 had NR. No patient experienced graft-versus-host disease (GVHD). With a median follow-up of 345 d (range, 129 to 784 d) post-transplantation, 18 patients remained alive and 4 had died (3 from primary disease relapse and 1 from cytomegalovirus pneumonia). The 2-year overall survival, disease-free survival, and cumulative incidence of tumor relapse post-transplantation were 75.2% ± 12.0%, 79.5% ± 9.4%, and 20.5% ± 9.4%, respectively. Our data indicate that the 2 strategies are effective for EF and do not result in GVHD or increase the risk of tumor relapse, but the MSC plus CB regimen has a superior effect on neutrophil reconstruction.

Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of patients with mixed-lineage-leukemia-rearranged acute leukemia: Results from a prospective, multi-center study.

The purpose of this study is to define the role for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in mixed-lineage-leukemia (MLL)-rearranged acute leukemia, which is now poorly understood. A prospective, multi-center cohort study to determine whether allo-HSCT could decrease relapse rates and improve long-term survival of MLL+ leukemia patients was performed. Fifty-six consecutive patients diagnosed with MLL-rearranged acute leukemia undergoing allo-HSCT from two transplant centers in China were enrolled between October 2007 and October 2012. The trial was registered at www.chictr.org as # ChiCTR-ONC-12002739. The incidences of grades II to IV acute graft versus host disease (aGVHD) and of grades III and IV aGVHD were 28.8% (CI, 16.87-40.8%), and 14.2% (CI, 5.4-23.0%), respectively. The cumulative incidences for chronic GVHD (cGVHD) at 2 years after HSCT were 35.2% (CI, 21.2-49.2%). Up to April 30, 2013, 12 patients had relapsed and 11 died from relapse, and 37 patients were still alive without disease recurrence. The relapse and NRM rates at 3 years were 25.3% (CI, 12.7-37.9%) and 18.0% (CI, 2.6-33.4%), respectively. The probalities of overall survival and leukemia free survival were 61.8% (CI, 46.0-77.6%) and 56.3% (CI, 38.1-74.5%) at 3 years, respectively. Patients transplanted during their hematological first complete remission (CR1) had a lower relapse rate (17.9% vs. 48.1%, P = 0.03) compared with patients transplanted beyond CR1. The median overall survival for the 29 patients not receiving allo-HSCT during the study period was 145 days from diagnosis. This study showed that allo-HSCT could be a valuable treatment choice for MLL+ acute leukemia.

Trafficking circuit of CD8+ T cells between the intestine and bone marrow governs antitumour immunity.

Immunotherapy elicits a systemic antitumour immune response in peripheral circulating T cells. However, the T cell trafficking circuit between organs and their contributions to antitumour immunity remain largely unknown. Here we show in multiple mouse leukaemia models that high infiltration of leukaemic cells in bone marrow (BM) stimulates the transition of CD8+CD44+CD62L+ central memory T cells into CD8+CD44-CD62L- T cells, designated as inter-organ migratory T cells (TIM cells). TIM cells move from the BM to the intestine by upregulating integrin ß7 and downregulating C-X-C motif chemokine receptor 3 during leukaemogenesis. Upon immunogenic chemotherapy, these BM-derived TIM cells return from the intestine to the BM through integrin α4-vascular cell adhesion molecule 1 interaction. Blocking C-X-C motif chemokine receptor 3 function boosts the immune response against leukaemia by enhancing T cell trafficking. This phenomenon can also be observed in patients with leukaemia. In summary, we identify an unrecognized intestine-BM trafficking circuit of T cells that contributes to the antitumour effects of immunogenic chemotherapy.

Hematopoietic stem cell transplantation activity in China 2022-2023. The proportions of peripheral blood for stem cell source continue to grow: a report from the Chinese Blood and Marrow Transplantation Registry Group.

Over past two years, a total of 39,918 hematopoietic stem cell transplantation (HSCT) cases were reported, with 18,194 and 21,714 transplants performed in 2022 and 2023, respectively. Autologous HSCT accounted for 6562 cases (31%) in 2022, while allogeneic HSCT comprised 12,632 cases (69%). In 2023, the number of allogeneic HSCTs exceeded 15,000, maintaining a 69% share. Participation in the 2022 and 2023 surveys included 193 and 212 transplantation teams, respectively, from 27 provinces, municipalities, or autonomous regions. The leading indication of HSCT was acute leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed phenotype acute leukemia, with a total of 17,421 cases. AML was the most common disease (10,339, 38%) for allogeneic HSCT, which was followed by ALL (5925 cases, 21%). Peripheral blood emerged as the primary source of stem cell grafts, utilized in 54% of matched sibling donor transplants and 77% of haploidentical donor transplants. The BuCy-based conditioning regimen was the most prevalent, used in 53% of allogeneic HSCT cases in the past two years. This survey offers a comprehensive overview of the current HSCT landscape and serves as a valuable resource for clinical practice.

Allo-HSCT for acute leukemia of ambiguous lineage in adults: the comparison between standard conditioning and intensified conditioning regimens.

Knowledge concerning the clinical and biological characteristics of acute leukemia of ambiguous lineage (ALAL) is limited so that there has been a lack of uniformity in treatment. In this report, we retrospectively investigated the effect of intensified conditioning on adult ALAL undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 59 patients with ALAL (male in 37 cases and female in 22 cases) were consecutively enrolled in the data analyses. Twenty-four patients received the standard conditioning (total body irradiation (TBI) + cyclophosphamide (CY) or busulfan + CY protocol) and 35 received the intensified conditioning (TBI + CY + etoposide or fludarabine + cytarabine plus TBI + CY + etoposide protocol). Five-year transplant-related mortality was 17.6 ± 9.6 % and 25.5 ± 8.0 %, the 5-year overall survival (OS) post-transplantation was 23.8 ± 8.9 % and 64.0 ± 8.4 %, disease-free survival was 16.7 ± 7.6 % and 55.8 ± 9.4 %, the 5-year cumulative incidence of relapse was 80.8 ± 8.5 % and 28.8 ± 9.9 %, respectively, in the standard and the intensified group (P = 0.380, P = 0.029, P = 0.005, and P < 0.001). Both univariate and multivariate analysis indicated that the intensified conditioning regimen and acute graft-versus-host disease were favorable factors to reduce the relapse. The younger patients, patients with CR at the time of transplantation, and the intensified conditioning regimen were favorable factors to elevate the survival. In conclusion, intensified conditioning regimens followed by allo-HSCT might improve long-term survival and decrease relapse of leukemia in adult ALAL compared to the standard conditioning regimens.

[Treatment efficacy of imatinib mesylate versus allogeneic hematopoietic stem cell transplantation for patients with chronic myeloid leukemia in chronic phase].

OBJECTIVE: To compare the treatment efficacy of imatinib mesylate versus allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with chronic myeloid leukemia in chronic phase. METHODS: The efficacy, overall survival, progression-free survival and adverse events were evaluated in 198 patients on these two therapies from February 2002 to December 2012 at our hospital. One hundred and fifteen cases in imatinib group (n = 115) received imatinib at an initial daily dose of 400 mg and then dose was adjusted according to blood routine test and therapy response. All patients were evaluated for hematologic, cytogenetic and molecular responses every 1-3 months. The allo-HSCT group (n = 83) received myeloablative preconditioning regimen and methotrexate (MTX) and cyclosporine A (CsA) were used for graft-versus-host disease (GVHD) partially plus mycophenolate mofetil (MMF) and antihuman thymocyte globulin (ATG). The engraftment evidence and evolution of cytogenetic and molecular response was conventionally detected after allo-HSCT. RESULTS: In imatinib group, 59 of 86 (68.6%) cases achieved complete cytogenetic response (CCyR) in the 12 months after therapy, while 67 of 70 (95.7%) cases achieved CCyR in allo-HSCT group. The relapse rates of two groups were 14.8% (17/115) , 12.3% (10/81) respectively. The adverse reaction of imatinib in imatinib group was obviously much more tolerable for patients compared with frequently occurred GVHD and infection in allo-HSCT group. The 10-year cumulative overall survival (OS) rate was 93.9% in imatinib group and 77.1% in allo-HSCT group (P = 0.015). And the 10-year cumulative progression-free survival (PFS) rate was 86.1% in imatinib group versus 88.0% in allo-HSCT group (P = 0.508) . For Sokal rating stratified analysis, the cumulative OS rates of two groups were 96.4% and 68.0% (P = 0.049) for intermediate-risk patients, 92.6% and 57.1% (P = 0.017) for high-risk patients while the cumulative PFS rates of two groups were 89.3% and 88.0% for intermediate-risk patients (P = 0.942), 70.4% and 85.7% for high-risk patients (P = 0.405). The rates of OS and PFS were not significantly different for low-risk patients. The cumulative OS rates of two groups were 94.7% and 73.5% (P = 0.009) for those ≥ 30 years old and the cumulative PFS rates of two groups 84.2% and 94.1% respectively (P = 0.147). CONCLUSION: Imatinib mesylate is superior to allo-HSCT for patients with chronic myeloid leukemia in chronic phase.

The novel HLA-B*40:01:78 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*40:01:78 differs from HLA-B*40:01:02:01 by one nucleotide in exon 3.