BACKGROUND: The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis. RESULTS: Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity ( P  <0.001 for all). Disease status (complete remission 1 [CR1] vs . ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups ( P  = 0.027; P  = 0.003; P  = 0.035; P  = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively ( P  <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival. CONCLUSION Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology* ; Neoplasm, Residual ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; Risk Factors ; Adolescent ; Adult ; Child ; Child, Preschool ; Young Adult ; Middle Aged ; Infant ; Transplantation, Homologous ; Proportional Hazards Models ; Retrospective Studies

Here we report the case of a CBF-AML patient with KIT p.D816V mutation who failed avapritinib induction therapy and subsequently underwent bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT), along with a literature review. The patient was a 64-year-old male who did not achieve remission after induction therapy with the DA regimen (Daunorubicin + Cytarabine). After reinduction with avapritinib combined with the DCHG regimen (Decitabine + Homoharringtonine + Cytarabine + Granulocyte colony-stimulating factor), he attained complete remission (CR) and flow cytometry minimal residual disease (MRD) negativity, but the RUNX1::RUNX1T1 fusion gene remained positive. During consolidation therapy, flow MRD reappeared, and the fusion gene level progressively increased. The patient then underwent a 9/10 HLA-matched unrelated donor allo-HSCT. Post-transplant, the fusion gene persisted, prompting treatment with the "ITI" regimen (with dose adjustments, including sequential addition of interferon and interleukin-2, pomalidomide incorporation, and standard vs. escalated dosing of "ITI" regimen). Currently, MRD negativity has been maintained for over 5 months, with good treatment tolerance. This finding suggest that the "ITI" regimen may serve as a novel and well-tolerated therapeutic option for CBF-AML patients with persistent RUNX1::RUNX1T1 fusion gene positivity after allo-HSCT and KIT p.D816V mutation, particularly in cases of avapritinib treatment failure.

Here we report the case of a CBF-AML patient with KIT p.D816V mutation who failed avapritinib induction therapy and subsequently underwent bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT), along with a literature review. The patient was a 64-year-old male who did not achieve remission after induction therapy with the DA regimen (Daunorubicin + Cytarabine). After reinduction with avapritinib combined with the DCHG regimen (Decitabine + Homoharringtonine + Cytarabine + Granulocyte colony-stimulating factor), he attained complete remission (CR) and flow cytometry minimal residual disease (MRD) negativity, but the RUNX1::RUNX1T1 fusion gene remained positive. During consolidation therapy, flow MRD reappeared, and the fusion gene level progressively increased. The patient then underwent a 9/10 HLA-matched unrelated donor allo-HSCT. Post-transplant, the fusion gene persisted, prompting treatment with the "ITI" regimen (with dose adjustments, including sequential addition of interferon and interleukin-2, pomalidomide incorporation, and standard vs. escalated dosing of "ITI" regimen). Currently, MRD negativity has been maintained for over 5 months, with good treatment tolerance. This finding suggest that the "ITI" regimen may serve as a novel and well-tolerated therapeutic option for CBF-AML patients with persistent RUNX1::RUNX1T1 fusion gene positivity after allo-HSCT and KIT p.D816V mutation, particularly in cases of avapritinib treatment failure.

Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.

Objective To investigate the correlation of peripheral blood lymphocyte, T-cell, Th-cell, and Ts-cell counts with the development of checkpoint-inhibitor-related pneumonitis in NSCLC. Methods The clinical data of 85 patients with NSCLC treated with immune checkpoint inhibitors (ICIs) were retrospectively analyzed.Paired t-test was used to analyze lymphocyte changes.ROC curves were utilized to analyze predictive performance.The Spearman correlation coefficient test was conducted to analyze the linear relationship between lymphocyte changes and CIP grade. Results A statistically significant decrease in lymphocyte, T-cell, Th-cell, and Ts-cell counts from the baseline was observed in patients at the onset of CIP (P < 0.05), whereas no such change was observed in the control group.ROC curve analysis revealed AUCs of 0.867, 0.843, 0.865, and 0.843 for lymphocyte, T-cell, Th-cell, and Ts-cell counts, respectively.A linear relationship was found between the percentage decrease in lymphocyte, T-cell, and Ts-cell counts from the baseline and the severity of CIP (P < 0.05). Conclusion Decreased lymphocyte, T-cell, Th-cell, and Ts-cell counts have a predictive value for the development of CIP, and the lymphocyte count change has the greatest predictive value.The percentage decrease in lymphocyte, T-cell, and Ts-cell counts from the baseline is correlated with the severity of CIP.

Objective:To investigate the long-term efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) as the first-line consolidation therapy for high-risk diffuse large B-cell lymphoma (DLBCL) in the rituximab era.Methods:From January 2010 to June 2017, 113 DLBCL patients admitted to Henan Cancer Hospital who had complete remission (CR) after rituximab combined with chemotherapy were enrolled. Among 113 patients, 40 cases received auto-HSCT as the first-line consolidation treatment after chemotherapy (transplantation group) and 73 cases received chemotherapy only (non-transplantation group). The clinical data of 113 patients were retrospectively analyzed. The overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method, and OS and PFS were compared between both groups.Results:The 2-, 3- and 5-year OS rates of transplantation group and non-transplantation group were 90.0% vs. 91.8%, 84.9% vs. 80.1%, 80.9% vs. 72.8%, respectively, and the difference in OS was statistically significant of both groups ( P = 0.457); the 2-, 3- and 5-year PFS rates were 85.0% vs. 85.0%, 82.2% vs. 61.8%, 82.2% vs. 60.0%, respectively, and the difference in PFS was statistically significant of both groups ( P = 0.046). None of the patients in the transplantation group experienced early transplantation-related death. Conclusions:In the era of rituximab treatment, the first-line auto-HSCT consolidation therapy could improve the PFS of high-risk DLBCL patients who are sensitive to chemotherapy, and it may improve the OS with a good safety.

Objective:To evaluate the efficacy and safety of upfront autologous hematopoietic stem cell transplantation(auto-HSCT)as a consolidation therapy of progressive nasal type extranodal NK/T-cell lymphoma, (ENKL).Methods:From January 2012 to June 2021, clinical data were retrospectively reviewed for 28 patients with advanced-stage ENKL on chemotherapy of asparaginase-containing regimen followed by upfront auto-HSCT as a consolidation therapy.The median age at transplantation was 34.5(14-61)years.There were 19 males and 9 females.Clinical types were nasal(n=22)and non-nasal(n=6). Clinical stages were Ann Arbor III(n=15)and IV(n=13). Clinical risks were intermediate(n=8)and high(n=20)according to the Prognostic Index for Natural-Killer cell lymphoma-Epstein-Barr virus(PINK-E).Results:Hematopoietic reconstruction was performed.Median time of neutrophil engraftment was 10(8-17)days and 13(10-22)days for platelet.Median follow-up time was 59.5 months and 5-year OS/PFS 70.0%(95% CI: 50.60%-89.40%)and 59.1%(95% CI: 39.11%-79.10%). And 5-year cumulative recurrence and non-recurrence mortality rates were 35.42%(95% CI: 19.11%-59.39%)and 4.2%(95% CI: 2.16%-29.87%). Conclusions:Asparaginase-based chemotherapy followed by auto-HSCT is both safe and efficacious for progressive ENKTL.

Objective:To evaluate risk factors and available treatments of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia.Methods:A total of 280 patients were retrospectively analyzed from January 2008 to December 2018 in Affiliated Cancer Hospital of Zhengzhou University. Clinical data were collected including disease patterns, pre-transplantation status, chromosome karyotype, conditioning regimen, types of donor, extramedullary disease before transplantation and graft-versus-host disease (GVHD). The log-rank test and Cox proportional hazard model were uesd for univariate analysis and multivariate analysis, respectively.Results:Twenty patients developed EMR (7.14%). The median time of EMR was 7.5 (1-123) months after allo-HSCT. The mortality of EMR was 80% (16/20). Univariate analysis identified disease patterns, second complete remission (CR2) or progressive disease before transplantation, extramedullary disease, abnormal karyotype and conditioning regimen without total body radiation as significant factors correlated to EMR ( P<0.05). Multi-variable analysis revealed that CR2 or progressive disease ( RR=3.468,95% CI 2.189-7.786), abnormal karyotype ( RR=1.494,95% CI 1.020-2.189) and extramedullary disease before transplantation ( RR=8.627,95% CI 3.921-18.452) were independent risk factors of EMR. Conclusions:The clinical outcome of EMR after allo-HSCT is poor.It is crucial to comprehensively assess and identify EMR as early as possible.

Objective:To explore the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed/refractory acute myeloid leukemia (AML).Methods:The clinical data of 35 patients with relapsed/refractory AML treated with allo-HSCT in the Affiliated Cancer Hospital of Zhengzhou University from June 2011 to October 2018 was retrospectively analyzed. The overall survival (OS), disease-free survival (DFS), graft versus host disease (GVHD) incidence, transplantation related mortality and recurrence rate were calculated, and the risk factors affecting prognosis were analyzed.Results:Hematopoietic reconstitution was obtained in all patients after transplantation. The 100 d incidence of grade Ⅱ-Ⅳ acute GVHD was (22.9±7.7)%, and the 3-year incidence of chronic GVHD was (49.5±10.60)%. The median follow-up time after transplantation was 14.1 months (4.2-89.4 months). In all cases, 18 cases survived (including 16 cases of DFS), and 17 cases died. Fourteen cases relapsed, and the median recurrence time was 4.7 months (2.9-32.4 months). The 3-year OS rate and DFS rate were (44.4±9.3)% and (43.0±9.5)%, respectively. Univariate analysis showed that the non-remission disease before transplantation, poor genetic risk grade before transplantation and recurrence after transplantation were the risk factors for OS (all P < 0.05). The 3-year OS rates in complete remission before transplantation group and non-remission before transplantation group were (63.2±12.0)% and (15.7±12.8)% ( P = 0.025), the 3-year DFS rates were (62.2±12.3)% and (15.3±12.7)% ( P = 0.028), and the 3-year recurrence rates were (28.2±10.7)% and (80.6±15.7)% ( P = 0.057). The 3-year recurrence rate in genetic high-risk group was higher than that in middle-risk group and low-risk group [100.0%, (45.0±12.1)% and (14.3±13.2)%, P = 0.045]. The 3-year tansplantation related mortality was (18.7±7.7)%. Conclusions:Allo-HSCT is an effective method for salvage treatment of relapsed/refractory AML, and recurrence is the main factor affecting survival. Reducing tumor load before transplantation is very important for reducing recurrence and improving curative effect.

Objective: To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) containing cladribine sequential busulfan regimen for refractory/relapsed acute myeloid leukemia (AML) . Methods: The clinical data of 12 refractory/relapsed AML patients received allo-HSCT with cladribine sequential busulfan regimen. Results: ① Of the 12 patients, 9 were males and 3 females, with a median age of 36 (27-50) years. The donors were identical sibling (3) , matched unrelated (1) and haploidentical family member (9) respectively. Nine patients reached partial remission and other remained no remission after chemotherapy before allo-HSCT. The median previous chemotherapy courses before allo-HSCT were 6 (2-13) . ② Conditioning regimen: Smostine 250 mg·m^-2·d^-1, d-7; Cladribine 5 mg·m^-2·d^-1, d-6 to d-2; Cytarabine Arabinoside 2 g·m^-2·d^-1, d-6 to d-2; Busulfan 3.2 mg·m^-2·d^-1, d-6 to d-3; Rabbit anti-human thymocyte immunoglobulin (ATG) 1.5 mg·m^-2·d^-1 (unrelated donor transplantation) or 2.0-2.5 mg·m^-2·d^-1 (haplo-HSCT) , d-4 to d-1. ③ Of the 12 patients, 11 patients attained complete haploidentical engraftment, one case occurred primary graft failure. The median durations for neutrophils and platelet implantations were 15 (15-21) and 19 (17-30) days respectively. ④After conditioning, no hepatic veno-occlusive diseases were observed, hemorrhagic cystitis occurred in 2 patients, 8 patients had fever, 3 cases experienced acute GVHD grade II, localized chronic GVHD occurred in 8 patients. ⑤The median follow-up was 8 (4-12) months. Leukemia relapse occurred in 2 patients at time of 6, 12 months after allo-HSCT. The estimated 1-year OS and DFS were (71.1±1.8) % and (62.2±1.8) %, respectively. Conclusions allo-HSCT with cladribine sequential busulfan regimen was a feasible choice with favorable outcome for refractory/relapsed AML.