Efficacy and safety of allogeneic hematopoietic stem cell transplantation in the treatment of 28 patients with hepatitis-related aplastic anemia / 中华血液学杂志

Objective: To evaluate the efficacy and safety of HLA-haploidentical hematopoietic stem cell transplantation (allo-HSCT) for hepatitis-related aplastic anemia (HRAA) patients. Methods: Retrospective analysis was performed on hepatitis-associated aplastic anemia patients who received haplo-HSCT at our center between January 2012 and June 2022. October 30, 2022 was the final date of follow-up. Results: This study included 28 HRAA patients receiving allo-HSCT, including 18 males (64.3% ) and 10 females (35.7% ), with a median age of 25.5 (9-44) years. About 17 cases of severe aplastic anemia (SAA), 10 cases of very severe aplastic anemia (VSAA), and 1 case of transfusion-dependent aplastic anemia (TD-NSAA) were identified. Among 28 patients, 15 patients received haplo-HSCT, and 13 received MSD-HSCT. The 2-year overall survival (OS) rate, the 2-year failure-free survival (FFS) rate, the 2-year transplant-related mortality (TRM) rate, the 100-day grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) cumulative incidence rate, and the 2-year chronic graft-versus-host disease (cGVHD) cumulative incidence rate were 81.4%, 81.4% (95% CI 10.5% -20.6% ), 14.6% (95% CI 5.7% -34.3% ), 25.0% (95% CI 12.8% -45.4% ), and 4.2% (95% CI 0.6% -25.4% ), respectively. After transplantation, all patients had no significant liver function damage. Compared with the MSD-HSCT group, only the incidence of cytomegaloviremia was significantly higher in the haplo-HSCT group [60.0% (95% CI 35.2% -84.8% ) vs 7.7% (95% CI 0-22.2% ), P=0.004]. No statistically significant difference in the Epstein-Barr virus was found in the 2-year OS, 2-year FFS, 2-year TRM, and 100-day grade Ⅱ-Ⅳ aGVHD cumulative incidence rates and 2-year cGVHD cumulative incidence rate. Conclusion: Allo-HSCT is safe and effective for HRAA, and haplo-HSCT can be used as a safe and effective alternative for newly diagnosed HRAA patients who cannot obtain HLA-matched sibling donors.

Effect and safety of 10-day decitabine-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation in 31 patients with acute myeloid leukemia/myelodysplastic syndrome / 中华血液学杂志

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.

Efficacy of basiliximab in the treatment of 87 cases of steroid-refractory or steroid-dependent acute graft-versus-host disease / 中华血液学杂志

Objective: To evaluate the efficacy and prognosis of basiliximab in the treatment of steroid-refractory or steroid-dependent acute graft-versus-host disease (SR/SD-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Clinical data of 87 patients with SR/SD-aGVHD in the skin, intestine, and liver after allo-HSCT at the Institute of Hematology & Blood Diseases Hospital Transplantation Center from January 2015 to December 2018 were retrospectively analyzed. The administration plan of basiliximab was as follows: 20 mg for adults and children weighing ≥35 kg and 10 mg for children weighing<35 kg. The drug was administered once on the 1st, 4th, and 8th days, respectively, and then once weekly. The efficacy was evaluated on the 7th, 14th, 21st, and 28th days after basiliximab treatment. Results: ①There were 51 males (58.6%) and 36 females (41.4%) , with a median (range) age of 34 (4-63) years. There were 54 cases of classic aGVHD, 33 of late aGVHD, 49 of steroid-refractory aGVHD, and 38 of steroid-dependent aGVHD. ②Thirty-five patients (40.2%) achieved complete remission (CR) , 23 (26.4%) achieved partial remission (PR) , and 29 had no remission (NR) . The total effective rate[overall response rate (ORR) ] was 66.7% (58/87) . ③The ORR of the classic and late aGVHD groups was 77.8% (42/54) and 48.5% (16/33) , respectively. ④The median (range) follow-up time was 154 (4-1813) days, the 6-month overall survival (OS) rate of the 87 patients was 44.8% (95% CI 39.5%-50.1%) and the 1-year OS was 39.4% (95%CI 34.2%-44.3%) . ⑤After treatment with basiliximab, the 6-month OS in the CR (35 cases) , PR (23 cases) , and NR (29 cases) groups was 80.0% (95%CI 73.2%-86.8%) , 39.1% (95%CI 28.9%-49.3%) , and 6.9% (95%CI 2.2%-11.6%) , respectively (χ(2)=34.679, P<0.001) , and the 1-year OS was 74.3% (95%CI 66.9%-81.7%) , 30.4% (95%CI 20.8%-40.0%) , and 3.4% (95%CI 0%-6.8%) , respectively (χ(2)=43.339, P<0.001) . The OS of the classic and late aGVHD groups was 57.4% (95%CI 50.7%-64.1%) and 24.2% (95%CI 16.7%-31.7%) , respectively (χ(2)=9.109, P=0.004) , and the 1-year OS was 51.9% (95%CI 45.1%-58.7%) and 18.2% (95%CI 11.5%-24.9%) , respectively (χ(2)=9.753, P=0.003) . ⑥Univariate and multivariate analyses showed that late aGVHD (OR=3.121, 95%CI 1.770-5.503, P<0.001) , Minnesota score high-risk group before medication (OR=3.591, 95%CI 1.931-6.679, P<0.001) , active infection before medication (OR=1.881, 95%CI 1.029-3.438, P=0.040) , and impairment of important organ function caused by non-GVHD (OR=3.100, 95%CI 1.570-6.121, P=0.001) were independent risk factors affecting the efficacy of basiliximab. Conclusion: Basiliximab has good efficacy and safety for SR/SD-aGVHD, but not in patients with late aGVHD, high-risk group of Minnesota score, and infection or impaired function of important organs.

Outcomes of 138 myelodysplastic syndrome patients with HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: ①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ(2)=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ(2)=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ(2)=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ(2)=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions: HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.

Outcomes and prognostic factors of myelodysplastic syndrome patients with allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To evaluate the outcomes and prognostic factors of myelodysplasia syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: 165 cases of MDS who underwent allo-HSCT from Jan. 2010 to Mar. 2018 were analyzed retrospectively, focusing on the overall survival (OS) , disease free survival (DFS) , relapse, non-relapse mortality (NRM) and their related risk factors. Results: Of all the 165 cases, 105 were male and 60 were female. The 3-year OS and DFS rate were 72.5% (95%CI 64.9%-80.1%) and 67.4% (95%CI 59.17%-75.63%) , respectively. The 3-year cumulative incidence of relapse and NRM were 12.11% (95%CI 7.03%-18.65%) and 20.44% (95%CI 14.15%-27.56%) , respectively. HCT-comorbidity index (P=0.042, HR=2.094, 95%CI 1.026-4.274) was identified as independent risk factor for OS by the multivariate analysis. Intensive chemotherapy before HSCT or hypomethylation agents treatment had no effects on OS[ (67.0±7.5) %vs (57.7±10.9) %, χ(2)=0.025, P=0.874]. Conclusions: allo-HSCT is a promising means for MDS, and NRM is the major cause of treatment failure. MDS with refractory anemia with excess blasts and secondary acute myeloid leukemia patients may not benefit from intensive chemotherapy or hypomethylation agents treatment before HSCT.

Decitabine-based conditioning regimen is feasible and effective in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia / 中华血液学杂志

Objective: To assess the efficacy and toxicity of decitabine-based conditioning regimen in patients with myelodysplastic syndrome (MDS) , acute myeloid leukemia secondary to MDS (MDS-AML) or chronic myelomonocytic leukemia (CMML) . Methods: From March 1, 2013 to May 25, 2015, 22 patients who underwent allogenic hematopoietic stem cell transplantation (allo-HSCT) with decitabine-based conditioning regimen were analyzed retrospectively. Results: ①22 patients, 14 males and 8 females with a median age of 42.5 (24-56) years old, were diagnosed as MDS (n=14) , CMML (n=4) , MDS-AML (n=4) . ②15 patients were treated with the conditioning regimen of decitabine combined with busulfan, cyclophosphamide, fludarabine, and cytarabine, the other 7 cases were treated with decitabine, busulfan, fludarabine, and cytarabine. The dose of decitabine was 20 mg·m(-2)·d(-1) for 5 days.Rabbit anti-human anti-thymocyte globulin (2.5 mg·kg(-1)·d(-1) for 4 days) was involved in conditioning regimen in patients with unrelated donor or haploidentical transplantation. ③Except 1 patient died of infection in 2 months after transplantation, the other patients were engrafted successfully. The median time of granulocyte engraftment was 13 (12-18) days, and the median time of platelet engraftment was 16 (13-81) days. ④The incidence of acute graft versus host disease (aGVHD) was (41.3±10.6) %, and severe aGVHD (grade of III-IV) was (18.4±9.7) %. The incidence of chronic graft versus host disease (cGVHD) was (56.4±11.3) %, and extensive cGVHD was (36.4±12.1) %. ⑤8 patients were suffered with cytomegalovirus (CMV) viremia. Among the 18 patients with definitely infection, 6 occurred during myelosuppression and 12 cases occurred after hematopoietic reconstruction. The 2-year and 3-year non-relapse mortality was (13.9±7.4) % and (24.3±9.5) %, respectively. ⑥The 2-year and 3-year overall survival (OS) was (77.3±8.9) % and (67.9±10.0) %, respectively. The 2-year and 3-year relapse-free survival (RFS) was (72.7±9.5) % and (63.6±10.3) %, respectively. Conclusions: allo-HSCT with decitabine-based conditioning regimen is feasible in the treatment of MDS, MDS-AML or CMML.

HLA-10/10 matched unrelated donor versus sibling donor hematopoietic stem cell transplantation for adult acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate the outcomes of human leukocyte antigen (HLA) matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT) for adult acute myeloid leukemia (AML) in a single center. Methods: Consecutive adult AML who received MUD-HSCT in our center from January 2008 to April 2017 were studied retrospectively, comparing with patients undergoing matched sibling donor (MSD) -HSCT in the same period. The rates of overall survival (OS) , disease free survival (DFS) , relapse, non-relapse mortality (NRM) , engraftment, acute and chronic graft-versus-host disease (aGVHD and cGVHD) were analyzed. Results: A total of 247 consecutive cases were enrolled, including 46 patients with MUD-HSCT and 201 with MSD-HSCT. All the patients experienced neutrophil engraftment except for one patient who died early in the MSD group, but the median day of engraftment was longer in the MUD group (15.0 vs 14.0, P=0.017) . The accumulative engraftment rate of platelet was comparable between the two groups (93.5%vs 98.0%, P=0.128) . The accumulative incidences of aGVHD (50.0%vs 46.3%, P=0.421) and cGVHD (37.8%vs 43.0%, P=0.581) were not statistically different between the two groups. Compared with the MSD group, the accumulative NRM rate at+36 months after transplantation was significantly higher in the MUD group (22.0%vs 10.4%, P=0.049) , while the relapse rate was not statistical difference (20.5 vs 28.3%, P=0.189) . Both the 3-year OS (61.6%vs 63.3%, P=0.867) and DFS (57.5%vs 61.6%, P=0.760) were comparable between the two groups. Four independent risk factors were confirmed by the multivariate analysis: patient age ≥45 years old, CR2 or NR before transplantation, a history of extramedullary infiltration and the occurrence of grade Ⅲ-Ⅳ aGVHD. No statistical differences were demonstrated in the survival rate between MUD-and MSD-HSCT in different subgroups. Conclusions: The outcomes, such as GVHD, relapse, OS and DFS, were comparable between MUD-and MSD-HSCT for adult AML, but higher incidence of NRM and longer time to neutrophil engraftment in the MUD group. MUD-HSCT is practical and feasible for adult AML who are lack of MSD.

The Effect of Serum Cytokine Levels prior Transplantation on the Outcome of Severe Aplastic Anemia Patients Received Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To identify the role of serum cytokine levels prior allogeneic hematopoietic stem cell trans-plantation (allo-HSCT) in the outcome of severe aplastic anemia (SAA) patients received allo-HSCT treatment.</p><p><b>METHODS</b>The clinical data of 117 SAA patients received allo-HSCT were enrolled in this study. The overall survival (OS), graft versus host disease (GVHD) incidence and relationship of serum cytokines with OS and major transplantation complications were retrospectively analyzed.</p><p><b>RESULTS</b>The patients enrolled in this study included 78(66.7%) cases received HSCT matched sibling donors (MSD), 12(10.2%) HSCT of unrelated donors (MUD) and 27 cases received HSCT of haploidentical donors (HID). The 5-years OS was 76.0%(95% CI: 64.4-87.5%); aGVHD cumulative incidence was 49.6%(95% CI: 40.4%-58.8%) and cumulative incidence cGVHD was 31.6%(95% CI:23.1%-40.2%). MSD allo-HSCT had a significantly higher 5-years OS as compared with the other donors(82.3%±6.6% vs 61.3%±11.7%, P<0.05). HLA matching, donor's age, cytomegalovirus/ Epstein-Barr virus (CMV/EBV) infection were important factors of affecting occurence of aGVHD. The patients with higher serum IL-6 had reduced platelet recovery time after transplantation (14.6±1.8 vs 18.3±2.6 d)(P=0.050) and higher serum TNF-α level accompanied by a lower incidence of CMV/EBV infection (37.8%±11.1% vs 58.8±16.8%)(P<0.05).</p><p><b>CONCLUSION</b>MSD allo-HSCT is the effective treatment for SAA patients. Donor's type remains the strong predictor of survival. The serum levels IL-6 and TNF-α before transplantation associate with platelet recovery and CMV/EBV infection.</p>

Prognostic significance of early phase donor chimerism after allogeneic peripheral blood stem cell transplantation / 中华血液学杂志

Objective: To evaluate the prognostic significance of early phase full donor chimerism (FDC) after myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: The clinical data of 72 hematological patients received myeloablative allo-PBSCT from Feb. 2016 to Jul. 2017 were analyzed retrospectively. The median age was 36.5 years (range 4-59), 44 were males and 28 females. Of the donors, there were 35 HLA matched sibling donors, 27 haploidentical donors and 10 unrelated donors. Polymerase chain reaction amplification of short tandem repeat sequence (PCR-STR) was used to detect donor cell chimerism (DC) rate of recipient bone marrow at one, two and three months after transplantation. Results: The median follow-up was 462 d (range: 47-805 d), 55 cases were still alive, and 45 cases were disease-free survival (DFS) at the end of follow-up. The 2-year overall survival (OS) and DFS were (68.9±7.7)% and (59.5±6.3)%, respectively. A number of 16 cases underwent relapses, with 2-year cumulative incidence of (24.1±5.3)%. The median time of recurrence was 157(32-374) d. Forty cases (55.6%) developed acute graft-versus-host diseases (aGVHD), with median time of 35.5 (13-90) d. Chronic GVHD (cGVHD) occurred in 23 patients (31.9%), with median time of 169 (94-475) d. Univariate analysis found the following factors were not related to OS, DFS or relapse rate (RR), including age, sex, blood type and sex of donor-recipient, occurrence of aGVHD and cGVHD. The OS and DFS in cases reached FDC and no FDC at two months after transplantation were (85.2±6.9)% vs (66.1±7.7)% (P=0.051) and (76.7±7.7)% vs (48.9±8.1)% (P=0.021), respectively. The RR rate in FDC group was lower than that in no FDC group [(16.6±6.8)% vs (30.4±7.8)%, P=0.187, respectively]. Conclusion: The present study confirmed the important value for predicting the prognosis with whether or not the patients reached FDC at the early phase after allo-PBSCT. The OS and DFS in cases with FDC at two months after transplantation were significantly higher than those of no FDC patients.

Outcome of acute myeloid leukemia with FLT3-ITD mutation treated by allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of acute myeloid leukemia (AML) patients with FLT3-ITD mutation. Methods: From September 2008 to December 2016, 40 AML patients with FLT3-ITD mutation were enrolled in the study. The therapeutic process, outcomes and prognostic factors were retrospectively analyzed. Results: The median of WBC at initial diagnosis was 35.0 (range 1.7-185.0) ×10(9)/L. The median course number of chemotherapy was 4 (range 2-7). At the time of transplantation, 34 patients were at the first complete remission (CR(1)) stage, and the other 6 ones were non-remission after chemotherapy. 24 patients received allogeneic transplants from an HLA-matched sibling donor, 7 cases from a HLA-matched unrelated donor, the remaining 9 ones received allograft from a haploidentical donor. The rate of 3-year overall survival (OS) and disease free survival (DFS) in all patients were both 74.3% (95% CI 60.4%-88.2%). The 3-year cumulative incidences of disease relapse and non-relapse mortality were 7.5% (95%CI 1.9%-18.4%) and 18.2% (95% CI 7.9%-32.0%), respectively. More than one course of chemotherapy before achieving CR(1) and the occurrence of acute GVHD after transplantation were associated with poor outcome in terms of OS and DFS. The relapse rates were significantly lower in patients receiving transplantation at CR(1) stage [0 vs 50.0% (95%CI 77.7%-82.9%) , P<0.001] and achieving CR(1) after one course induction therapy [0 vs 16.7% (95%CI 3.9%-37.3%) , P=0.020]. Conclusions: Allo-HSCT was an efficient approach for AML patients with FLT3-ITD mutation. Patients obtained better survival, especially for those achieving CR after one course induction therapy and receiving transplantation at CR(1) stage.

Application of low-dose ATG for GVHD prophylaxis in patients undergoing PBSCT aged over forty years old / 中华血液学杂志

Objective: To explore the effectiveness of a novel GVHD prophylaxis regimen containing low-dose anti-T lymphocyte globulin (ATG) in patients undergoing peripheral blood stem cell transplantation (PBSCT) from HLA-matched sibling donors (MSD) given both the patients and donors were aged over forty years old. Methods: From March 2013 to April 2017, 98 patients with hematologic malignancies were enrolled in the study. Standard GVHD prophylaxis consisted of the administration of cyclosporine A/tacrolimus and a short course of methotrexate. In ATG group, 43 patients received low-dose rabbit ATG (Sanofi, 1.5 mg/kg per day for 3 consecutive days) before PBSCT. A retrospective matched-pair analysis was performed and 55 matched controls were available. The therapeutic process and clinical outcome were retrospectively analyzed. Results: ①Neutrophil engraftment was achieved earlier in ATG group than the control one [13(11-17)d vs 14(12-24)d, P=0.001]. The time to platelet engraftment was similar between the two groups [14(11-43)d vs 15(11-42)d, P=0.071]. ②The cumulative incidence of aGVHD was significantly lower in ATG group [25.6% (95%CI 13.7%-39.3%) vs 49.1% (95%CI 35.2%-61.6%), P=0.018]. The incidences of grade Ⅱ-Ⅳ aGVHD [18.6% (95%CI 8.6%-31.5%) vs 23.6% (95%CI 13.4%-35.6%), P=0.509] and cGVHD [49.6% (95% CI 31.6%-65.3%) vs 56.4% (95% CI 41.4%-69.0%), P=0.221] were not significantly different between the two groups. ③The 1-year cumulative incidence of CMV viremia was similar between the two groups [21.1%(95%CI 10.3%-34.5%) vs 31.1% (95%CI 18.8%-44.2%), P=0.429]. ④The cumulative incidences of disease relapse [24.0%(95%CI 11.5%-38.9%) vs 24.0% (95% CI 12.1%-38.2%), P=0.608), non-relapse mortality [10.2% (95% CI 3.1%-22.1%) vs 21.6% (95% CI 9.4%-37.0%), P=0.411] and DFS [65.8% (95%CI 50.3%-81.3%) vs 54.4% (95%CI 37.7%-71.1%), P=0.955] were comparable between the two groups. 2-year overall survival (OS) was significantly better in ATG group than the control one [83.8% (95% CI 71.8%-90.0%) vs 58.0% (95% CI 42.2%-73.9%), P=0.019]. Conclusion: The addition of low-dose ATG decreased the incidence of aGVHD and improved OS. The incidences of viral infections and disease relapse remained to be similar between the two groups. These results suggested that elderly patients undergoing MSD-PBSCT may benefit from this low-dose ATG containing GVHD prophylaxis regimen.

Effects of preexisting donor-specific HLA antibodies for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To investigate the effects of donor-specific HLA antibodies(DSA) for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT) and the feasible treatment for DSA. Methods: HLA antibodies were examined using the Luminex-based single Ag assay for 92 patients who were going on haplo-SCT and the correlations of graft failure and DSA among the patients who had finished SCT were analyzed. Results: Of the total 92 patients who were going on haplo-HSCT, sixteen (17.4%) patients were HLA Ab-positive, including six (6.5%) patients with antibodies corresponding to donor HLA Ags (DSA-positive). Among the patients who had finished the haplo-HSCT with conventional myeloablative conditioning regimen, the engraftment rate was significantly higher in DSA (-) patients than that in DSA (+) patients [92.3% (24/26) vs 25.0%(1/4), χ2=8.433, P=0.004] and DSA was the only factor relevant with graft failure in multiple-factor analysis [OR=12.0(95% CI 1.39-103.5), P=0.024]. Strategies to decrease antibody levels were taken for 4 patients, two were their first transplantations, and the other two patients were their second haplo-HSCT. Three of the four patients were HLA-I-DSA positive and had gained donor engraftment by means of donor platelet transfusions to decreased the level of DSA, the fourth patient with both HLA-I and HLA-II DSA also gained engraftment with the treatments of TBI, rituximab and donor platelet transfusion. Conclusion: DSA is one of the key factors of graft failure in haplo-HSCT. Donors should be selected on the basis of an evaluation of HLA antibodies before transplantation. If haplo-HSCT from donors with DSA must be performed, then recipients should be treated for DSA to improve the chances of successful engraftment.

Clinical efficacy and safety of porcine antihuman lymphocyte immunoglobulin in alternative donor allogeneic hematopoietic cell transplantation for severe aplastic anemia / 中华血液学杂志

Objective: To compare eficacy and safety of porcine antihuman lymphocyte immunoglobulin (pALG) and rabbit antithymocyte immunoglobulin (rATG) as a part of alternative donor allogeneic hematopoietic stem cell transplantation (AD allo-HSCT) for severe aplastic anemia (SAA). Methods: The clinical data of 46 SAA patients received AD allo-HSCT from January 2006 to November 2016 were retrospectively analyzed. The cohort of patients were divided into two groups based on rATG or pALG as a part of conditioning regimen to compare implantation rate, transplantation related complications and outcome. Results: In rATG group 30 patients achieved ANC reconstitution, 27 patients achieved PLT reconstitution. In pALG group all 16 patients achieved ANC and PLT reconstitutions. There were no significant differences between the two groups in terms of acute graft-versus-host disease (aGVHD) (P=0.475), Ⅲ-Ⅳ grade aGVHD (P=0.876), chronic GVHD (cGVHD) (P=0.309), extensive cGVHD (P=0.687), graft rejection (GR) (P=0.928), bloodstream infection (P=0.443), invasive fungal disease (P=0.829), cytomegalovirus viremia (P=0.095) respectively. Prospective 5-year overall survival (OS) in rATG and pALG groups were (75.1±8.2)% and (53.6±13.3)% with median follow-up of 14(2-102) and 23(4-63) months, respectively (P=0.190). Conclusion: As a part of conditioning regimen, pALG could achieve similar efficacy as rATG, without increasing the incidences of transplantation complications such as GVHD, GR and infection, in the setting of AD allo-HSCT for SAA patients.

Outcomes of Adults with Acute Lymphoblastic Leukemia After Autologous Hematopoietic Stem Cell Transplantation and the Significance of Pretransplantation Minimal Residual Disease: Analysis from a Single Center of China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The postremission therapies for adult patients generally contain consolidation chemotherapy, allogeneic hematopoietic stem cell transplantation and autologous hematopoietic stem cell transplantation (auto-HSCT). Because of the various results from different centers, the optimal therapy for adult acute lymphoblastic leukemia (ALL) patients is still uncertain. This study aimed to better understand predictive factors and role of auto-HSCT in the postremission therapy for adult ALL patients.</p><p><b>METHODS</b>The outcomes of 135 adult patients with ALL, who received the first auto-HSCT in Hematopoietic Stem Cell Transplantation Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 1994 to February 28, 2014, were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method and simultaneous effects of multiple covariates were estimated with the Cox model.</p><p><b>RESULTS</b>Overall survival (OS) and disease-free survival (DFS) at 5 years for the whole cohort were 59.1 ± 4.5% and 59.0 ± 4.4%, respectively. The cumulative nonrelapse mortality and relapse rate at 5 years were 4.5 ± 0.03% and 36.6 ± 0.19%. For both OS and DFS, acute T-cell lymphoblastic leukemia, high lactate dehydrogenase (LDH) at diagnosis, blast cell proportion ≥5% on the 15 th day of induction therapy, and extramedullary infiltration before HSCT were the poor prognosis factors. In addition, age ≥35 years predicted poor DFS. Only T-ALL and high LDH were the independent undesirable factors associated with OS and DFS in Cox regression model. For 44 patients who had results of pretransplantation minimal residual disease (MRD), positive MRD (MRD ≥0.01%) indicated poor OS (P = 0.044) and DFS (P = 0.008). Furthermore, for the standard risk group, the patients with negative MRD (MRD <0.01%) had better results (OS at 18 months was 90.0 ± 9.5%, while for the patients with positive MRD OS was 50.0 ± 35.4%, P = 0.003; DFS at 18 months was 90.0 ± 9.5%, while for the positive MRD group DFS was 0%, P < 0.001).</p><p><b>CONCLUSIONS</b>This study confirmed that auto-HSCT combined with posttransplantation maintenance chemotherapy could be an option for adult ALL patients and pretransplantation MRD may play a significant role in the direction of therapy for adult ALL patients.</p>

Analyses of risk factors for intestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the risk factors of intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The clinical data of 534 cases of 533 patients undergoing allo-HSCT during Jan 2004 and Sep 2012 were retrospectively analyzed. The effects of donor-recipient HLA mismatching, recipient age, donor age, donor-recipient sex combination, donor-recipient relationship, HSC source, conditioning regimen with or without total body irradiation (TBI) and HLA loci on intestinal aGVHD with different severity were analyzed by Logistic regression.</p><p><b>RESULTS</b>Intestinal aGVHD occurred in 123(23.0%) cases, with 86(16.1%) cases of stage 1 intestinal aGVHD(16.1%) and 37(6.9%) cases of stage 2 to 4 intestinal aGVHD. Multivariate analysis showed that donor-recipient HLA mismatching (OR=2.519, P=0.002), increasing donor age (OR=1.034, P=0.003), female donor for male recipient (OR=1.855, P=0.007) were risk factors for intestinal aGVHD, HLA-B38 (OR=0.256, P=0.032) was its protective factor. Donor-recipient HLA mismatching (OR=2.799, P=0.011), increasing donor age (OR=1.045, P=0.012), HLA-A1 (OR=4.157, P=0.002), A30 (OR=3.143, P=0.005) were risk factors for stage 2 to 4 intestinal aGVHD.</p><p><b>CONCLUSION</b>Occurrence of intestinal aGVHD and its severity are associated with donor-recipient HLA mismatching, donor age, donor-recipient sex relationships and some HLA loci.</p>

Prophylaxis of invasive fungal infection with different administration regimens of itraconazole in patients with acute myeloid leukemia: a report from a randomized, controlled trial / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of antifungal prophylaxis of itraconazole in patients with acute myeloid leukemia (AML) to probe the relationship of the antifungal effect and the adverse events with serum concentration.</p><p><b>METHODS</b>From April 2009 to May 2011, a total of 310 courses from 112 patients referred to our institute were enrolled in this study; of them, 297 courses were eligible for analysis. Eligible cases were randomized into oral group and injection/oral group according to different chemotherapy of induction and consolidation. Blood samples were collected at different time points for measurements of serum itraconazole levels. The morbidity of IFI and the adverse events were analyzed.</p><p><b>RESULTS</b>The morbidities of IFI in injection/oral and oral groups were 10.1% and 20.9%, respectively (P=0.010). 7 and 9 cases in injection/oral and oral groups, respectively were withdrawn from the study because of adverse events, and the difference between these two groups was of no significance. Serum itraconazole levels of injection/oral and oral groups were 672(299-1097) μg/L and 534(210-936) μg/L, respectively (P<0.01).</p><p><b>CONCLUSION</b>Antifungal prophylaxis with itraconazole in AML patients was effective and safe. Prophylactic effect with injection/oral itraconazole was superior to oral itraconazole solution; moreover, prophylactic effect of itraconazole was highly correlated with its serum level.</p>

Outcome of allogeneic hematopoietic stem cell transplantation from HLA-matched sibling donor for 41 cases of severe aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched sibling donor (MSD allo-HSCT) for severe aplastic anemia (SAA).</p><p><b>METHODS</b>The clinical data of 41 SAA patients received MSD allo-HSCT from May. 2003 to Aug. 2011 were analyzed retrospectively. 24 patients were male, 17 were female. Median age was 23 (5 - 43) years old. 28 patients had SAA-I, 9 had SAA-II, and 4 had post-hepatitis aplastic anemia. 17 patients received allogeneic bone marrow (BM) transplantation (allo-BMT), and 24 received allogeneic peripheral blood stem cell (PBSC) transplantation (allo-PBSCT). The conditioning regimens: 20 patients received cyclophosphamide (CY) + anti-thymocyte globulin (ATG) + fludarabine (Flu), 21 received CY + ATG + Flu+ cytarabine (Ara-C) ± busulfan (Bu)/melphalan (Mel). Prophylaxis for graft-versus-host disease (GVHD): 25 patients received cyclosporine (CSA) plus short-term methotrexate (MTX), 16 received tacrolimus (FK506) plus short-term MTX. The median number of infused CD34(+) cells were 3.48 (2.39 - 4.80)×10(6)/kg in allo-BMT and 2.95 (1.27 - 5.98)×10(6)/kg in allo-PBSCT, respectively.</p><p><b>RESULTS</b>Hematopoietic reconstitution was observed in all 41 patients (100%). The median time of neutrophils (ANC) reached to 0.5×10(9)/L and platelets (PLT) reached to 20×10(9)/L were 14 (10 - 23) days and 19 (8 - 38) days, respectively. 12 patients developed acute GVHD (aGVHD), out of which 11 developed grade I-II aGVHD, and one developed grade IV. 2 patients occurred chronic GVHD (cGVHD), out of which one with local cGVHD and the other with extensive. 4 patients occurred graft rejection (GR), all of them recovered haemopoiesis and survived after donor PBSC infusion. 5 patients (12.2%) died, out of which one died of extensive cGVHD, and 4 died of invasive fungal infections (IFI). Median follow-up time was 23 (3 - 79) months. 36 patients survived. 5-year estimated overall survival (OS), disease free survival (DFS), and transplant-related mortality (TRM) was (81.1 ± 9.0)%, (68.4 ± 11.0)%, and (18.9 ± 9.0)%, respectively. Univariate analysis showed that lover OS had significant correlation with receiving PBSCT, occurrence of aGVHD, the number of infused CD34(+) cells no more than 2.5×10(6)/kg, the number of red blood cell (RBC) transfusion before transplant more than 30 U and occurrence of IFI after transplantation (P = 0.034, 0.001, 0.006, 0.000, 0.001, respectively). Occurrence of aGVHD had significant correlation with the disparity between donor and recipient ABO blood groups, the number of PLT transfusion more than 100 U, and the number of RBC transfusion more than 30 U before transplantation, the number of infused CD34(+) cells no more than 2.5× 10(6)/kg (P = 0.019, 0.038, 0.005, 0.005, respectively). The occurrence of GR had significant correlation with the number of PLT transfusion more than 100 U before transplantation (P = 0.038).</p><p><b>CONCLUSION</b>MSD allo-HSCT is an effective therapy for patients with SAA. Lower number of blood transfusion before transplantation, use of BMT, more number of infused CD34(+) cells can effectively prevent and treat aGVHD and IFI after transplantation, which may improve the efficacy of MSD allo-HSCT for SAA.</p>

Role of IFN-γ + 874 genetic polymorphisms in allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the impact of IFN-γ + 874 polymorphisms on the outcome in HLA matched sibling HSCT.</p><p><b>METHODS</b>We used PCR-sequence-specific primer analysis (PCR-SSP) to analyze the polymorphisms of IFN-γ + 874 T/A in 80 recipient and donor pairs from October 2005 to March 2008.</p><p><b>RESULTS</b>Recipients having donors who possessed IFN-γ + 874 A/A genotype had significantly earlier neutrophil recovery compared with those having donors with non-A/A genotype (15 (11 - 27) days vs 18 (12 - 30) days, P = 0.029). And IFN-γ + 874 A/A in both recipients and donors further facilitated neutrophil recovery compared with others (13 (11 - 25) days and 19 (12 - 31) days, P = 0.019). Besides, IFN-γ + 874 A/A in recipients increased the probability of grade II-IV acute graft versus disease (aGVHD) and cytomegalovirus viraemia compared with IFN-γ + 874 T/A or T/T genotype (20% vs 4% P = 0.041, 43.6% vs 16.0% P = 0.032), which lead to increased 5-year transplant-related mortality (TRM) (33.7% ± 6.8% vs 12.0% ± 6.5%, P = 0.050) and decreased 5-year event free survival (EFS) \[(58.2 ± 6.7)% vs (84.0 ± 7.3)%, P = 0.032\] compared with the latter. IFN-γ + 874 A/A in both recipients and donors also significantly increased the probability of grade II-IV aGVHD and cytomegalovirus viraemia compared with the other (21.7% vs 5.9%, P = 0.050; 45.7% vs 20.6%, P = 0.020), which caused increased 5-year TRM \[(31.6 ± 7.5)% vs (13.6 ± 6.5)%, P = 0.048\] and decreased 5-year EFS \[(56.8 ± 7.3)% vs (79.4 ± 6.9)%, P = 0.037\] compared with the other.</p><p><b>CONCLUSION</b>In HLA-matched sibling HSCT setting, the presence of IFN-γ + 874 T allele in recipients or in both recipients and donors significantly decreased the risk of grade II-IV aGVHD and CMV infection and increased EFS. While IFN-γ + 874 A/A in donors or in both recipients and donors was associated with shorter duration to neutrophil recovery.</p>

Risk factors and prognosis of invasive fungal infections in patients with hematological diseases / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the incidence, risk factors, prognosis and high risk patients of invasive fungal infections (IFI) in patients with hematological diseases.</p><p><b>METHODS</b>: Over 2-week hospitalized patients from January 2007 to December 2008 were retrospectively reviewed. Logistic regression was used to analyze the risk factors of IFI, and recursive partitioning to reveal high risk patients. Incidence of IFI was estimated by cumulative incidence function, and the prognosis by Kaplan-Meier method.</p><p><b>RESULTS</b>A total of 1048 assessable treatment cycles were recorded and 93 cases of IFI were diagnosed, with an incidence of 8.87 per 100 treatment cycles. Multivariate logistic regression revealed the following risk factors: age (OR 1.025, 95% CI 1.010-1.041, P = 0.002), duration of neutropenia (OR 1.028, 95% CI 1.014-1.042, P < 0.0001) and uncontrolled underlying diseases (OR 2.620, 95% CI 1.608-4.268, P = 0.0001). Recursive partitioning found two groups of high risk patients: (1) patients with uncontrolled underlying diseases and neutropenia duration > or = 58 days (7/12, 58.3%), (2) patients with uncontrolled underlying diseases and age > or = 33 years (40/208, 19.2%). At the end of follow-up, 111 cases of IFI were recorded in 451 patients, with a 1-year cumulative incidence of 27.1%. In patients with established IFI, overall survival rate and IFI related mortality rate at 12 weeks after diagnosis were 83.4% and 13.5% respectively.</p><p><b>CONCLUSION</b>Age, duration of neutropenia and uncontrolled underlying diseases are risk factors of IFI; patients with uncontrolled underlying diseases and age > or = 33 years were at high risk of IFI and need major concern. IFI has a better prognosis and a lower related mortality in this study.</p>

Preliminary analysis of therapeutic efficacy and prognosis of allogeneic hematopoietic stem cell transplantation in patients with advanced chronic myeloid leukemia / 中国实验血液学杂志

Chronic myeloid leukemia (CML) at advanced and blastic phase is a disease with poor prognosis, for which allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment choice with curative potential. This study was purposed to investigate the therapeutic efficacy of allo-HSCT and prognosis of advanced CML patients. The 28 cases of CML in accelerated phase or blast crisis received allo-HSCT were analysed retrospectively in terms curative efficacy, basic characteristics before transplant and prognosis, therapeutic strategy before transplant and prognosis, events after transplant and prognosis. The results indicated that 10 out of 28 patients were in complete remission, showing a 3-year overall survival and disease-free survival rate of 34.9% and 35.7% respectively; 18 patients died. Univariate analysis revealed that the clonal evolution and blast amount are baseline risk factor of poor prognosis, and combination of them can be used to predict the outcome of patients; application of imatinib before transplant and achievement of complete hematologic remission could not improve the prognosis; severe aGVHD among post-transplant events was proven to be a negative prognostic factor. It is concluded that for advanced CML patients received allo-HSCT, clonal evolution and blast percentage are prognostic factors, and the pre-transplant use of imatinib did not influence the outcome.