Clinical Significance of Pulmonary Function Tests in Long-Term Survivors after Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation

We retrospectively assessed long-term pulmonary function in adults surviving for ≥5 years after myeloablative allogeneic hematopoietic stem cell transplantation and identified risk factors for late-onset noninfectious pulmonary complications. Among 174 patients undergoing transplantation for hematologic malignancies between May 1994 and December 2004, 81 long-term survivors were evaluated. Pulmonary function tests (PFTs) were performed before conditioning, 3 months and 1 year after transplantation, and then annually. Eight patients (10%) had abnormal pulmonary function before transplantation, but this was not associated with late changes in PFTs. Patients with chronic graft-versus-host disease (GVHD) showed a significant decline of lung function after 3 years when compared with patients without chronic GVHD. Abnormal pretransplantation lung function was associated with pulmonary chronic GVHD according to National Institutes of Health criteria (score 0, n = 58;score 1, n = 14;score 2, n = 6;score 3, n = 3). Five patients with late-onset noninfectious pulmonary complications showed a decline of lung function at 1 year after transplantation. Only chronic GVHD was significantly related to late-onset noninfectious pulmonary complications. In conclusion, abnormal lung function before transplantation may be associated with a decline in pulmonary function within 1 year after transplantation, but late-onset noninfectious pulmonary complications could not be predicted from pretransplantation lung function.

Comparison of the clinical outcomes of hematologic malignancies after myeloablative haploidentical transplantation with G-CSF/ATG and posttransplant cyclophosphamide:results from the Chinese Bone Marrow Transplantation Registry Group(CBMTRG)

This study compared G-CSF/ATG and PTCy in myeloablative haploidentical hematopoietic stem cell transplantation(haploHSCT)for hematologic malignancies between January 2013 and March 2018 reporting to the Chinese Bone Marrow Transplantation Registry Group(CBMTRG).For each PTCy,G-CSF/ATG subjects(1:4)were selected using the nested case-pair method.In total,220 patients including 176 in G-CSF/ATG group and 44 in PTCy group were analyzed.The incidences of 30-day neutrophil engraftment(88.6%vs.96.6%,P=0.001),90-day platelet engraftment(84.1%vs.94.2%,P=0.04),the median time to neutrophil engraftment(17 days vs.12 days,P=0.000)and platelet engraftment(22 days vs.17 days,P=0.001)were significantly inferior in PTCy group.The incidences of grades 2–4 and 3–4 acute graft-versus-host disease(GVHD),chronic GVHD and severe chronic GVHD were comparable.Among G-CSF/ATG and PTCy groups,the 3-year progression-free survival,overall survival,cumulative incidences of nonrelapse mortality and relapse was 74.3%vs.61%(P=0.045),78.3%vs.65.2%(P=0.039),12%vs.27.3%(P=0.008),and 14.9%vs.11.7%(P=0.61),respectively.G-CSF/ATG can achieve better engraftment,PFS and OS,and lower incidence of NRM compared to PTCy in myeloablative haplo-HSCT for hematologic malignancies.

Allogeneic hematopoietic stem cell transplantation with the modified myeloablative conditioning regimen for children with chronic active Epstein–Barr virus infection

Importance:Allogeneic hematopoietic stem cell transplantation(alloHSCT)is considered the only effective treatment for chronic active Epstein–Barr virus infection(CAEBV).The clinical efficacy and safety of allo-HSCT with different conditioning regimens in children with CAEBV remain unclear.Objective:To evaluate the effectiveness and safety of allo-HSCT with the modified myeloablative conditioning(MAC)regimen for children with CAEBV and also the factors affecting the outcomes.Methods:We retrospectively analyzed children with CAEBV who underwent allo-HSCT with the modified MAC regimen at Beijing Children’s Hospital,Capital Medical University from October 2016 to June 2021.Data related to the clinical manifestations,engraftment,and outcome were extracted from the medical records.Results:The cohort comprised 41 patients(24 males,17 females)with a median transplantation age of 92.6(60.4,120.7)months and a median follow-up time of 28.2(15.3,40.2)months.Four patients(9.8%)died,among which three died from primary disease relapse,and one died from grade IV acute graft-versus-host diseases(aGVHD)after stopping treatment.The 3-year overall survival(OS)and 3-year event-free survival(EFS)rates were 88.8%±5.4%and 85.0%±5.7%,respectively.The 3-year OS and EFS did not significantly differ between the patients with hemophagocytic lymphohistiocytosis(HLH)and the patient without HLH(87.7%±6.8%vs.91.7%±8.0%,P=0.790;85.0%±6.9%vs.84.6%±10.0%,P=0.921),or among the patients with complete remission,partial remission,and activity disease before HSCT(all P>0.05).Multivariate analysis showed that grade III–IV aGVHD was a risk factor for mortality(Hazards ratio:11.65,95%confidence interval:1.00,136.06;P=0.050).Interpretation:Allo-HSCT with the modified MAC regimen is safe and effective for pediatric CAEBV.This treatment benefits patients with HLH or active disease.Patients with Grade III–IV aGVHD may be associated with worse outcomes.

WJSC 6^(th) Anniversary Special Issues(1):Hematopoietic stem cell transplantation Allogeneic hematopoietic cell transplant for acute myeloid leukemia:Current state in 2013 and future directions

Acute myeloid leukemia(AML)represents a heterogeneous group of high-grade myeloid neoplasms of the elderly with variable outcomes.Though remissioninduction is an important first step in the management of AML,additional treatment strategies are essential to ensure long-term disease-free survival.Recent pivotal advances in understanding the genetics and molecular biology of AML have allowed for a risk-adapted approach in its management based on relapse-risk.Allogeneic hematopoietic cell transplantation(allo-HCT)represents an effective therapeutic strategy in AML providing the possibility of cure with potent graft-versus-leukemia reactions,with a demonstrable survival advantage in younger patients with intermediate-or poor-risk cytogenetics.Herein we review the published data regarding the role of allo-HCT in adults with AML.We searched MEDLINE/PubMed and EMBASE/Ovid.In addition,we searched reference lists of relevant articles,conference proceedings and ongoing trial databases.We discuss the role of allo-HCT in AML patients stratified by cytogenetic-and molecular-risk in first complete remission,as well as allo-HCT as an option in relapsed/refractory AML.Besides the conventional sibling and unrelated donor allografts,we review the available data and recent advances for alternative donor sources such as haploidentical grafts and umbilical cord blood.We also discuss conditioning regimens,including reduced intensity conditioning which has broadened the applicability of allo-HCT.Finally we explore recent advances and future possibilities and directions of allo-HCT in AML.Practical therapeutic recommendations have been made where possible based on available data and expert opinion.