Search

Using traditional statistical methods, we previously analyzed the risk factors and treatment outcomes of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after allogeneic hematopoietic cell transplantation. Within the same cohort, we applied machine learning to create prediction and recommendation models. We analyzed 2572 transplants using eXtreme Gradient Boosting (XGBoost) to predict post-transplant VOD/SOS and early death. Using the XGBoost and SHapley Additive exPlanations (SHAP), we found influential factors and devised recommendation models, which were internally verified by repetitive ten-fold cross-validation. SHAP values suggested that gender, busulfan dosage, age, forced expiratory volume, and Disease Risk Index were significant factors for VOD/SOS. The areas under the receiver operating characteristic curves and the areas under the precision-recall curve of the models were 0.740, 0.144 for all VOD/SOS, 0.793, 0.793 for severe to very severe VOD/SOS, and 0.746, 0.304 for early death. According to our single feature recommendation, following the busulfan dosage was the most effective for preventing VOD/SOS. The recommendation method for six adjustable feature sets was also validated, and a subgroup corresponding to five to six features showed significant preventive power for VOD/SOS and early death. Our personalized treatment set recommendation showed reproducibility in repetitive internal validation, but large external cohorts should prospectively validate our model.

Given the controversies in the prognostic value of KIT mutations and optimal thresholds and time points of MRD monitoring for AML with CBFB-MYH11, we retrospectively evaluated 88 patients who underwent allogeneic hematopoietic stem cell transplantation (Allo-HSCT, n = 60) or autologous HSCT (Auto-HSCT, n = 28). The D816V KIT mutation was significantly associated with post-transplant relapse, contrasting with other types of mutations in KIT. Pre- and post-transplant (3 months after transplant) CBFB-MYH11 MRD assessments were useful in predicting post-transplant relapse and poor survival. The optimal threshold was determined as a 2 log reduction at both time points. In multivariate analysis, the D816V KIT mutation and CBFB-MYH11 MRD assessments were independently associated with post-transplant relapse and survival. Stratification by D816V KIT and pre-transplant CBFB-MYH11 MRD status further distinguished the risk of relapse and survival. Auto-HSCT was superior to Allo-HSCT in MRD negative patients without D816V KIT, while Allo-HSCT trended to be superior to Auto-HSCT in patients with MRD positivity or the D816V KIT mutation. In conclusion, this study demonstrated the differentiated prognostic value of the D816V KIT mutation in AML with CBFB-MYH11 and clarified optimal time points and thresholds for CBFB-MYH11 MRD monitoring in the setting of HSCT.

We attempted to identify the incidence and survival outcome of hepatic sinusoidal obstruction syndrome/veno-occlusive disease (VOD/SOS) after hematopoietic cell transplantation (HCT) under strategy of prophylactic ursodiol and intravenous heparin or prostaglandin E1 (PGE1). From 2009 to 2018, 2572 consecutive allogeneic-HCT cases were reviewed. We used oral ursodiol for all transplants, and most were administered low-dose heparin, while PGE1 in selected cases with low platelet count at the time of preconditioning. Diagnosis and severity grades were reassessed by revised EBMT criteria. The overall incidence of hepatic VOD/SOS was 3.4% (Mild 0.9%, Moderate 0.6%, Severe 0.7%, Very severe 1.2%) after allogeneic-HCT under strategy of intravenous prophylaxis. The 1-year overall survival of VOD/SOS was 41.4% which was divided into 73.9% for mild, 66.7% for moderate, 38.9% for severe, and 6.5% for very severe grade. Very high disease risk index, male gender, donor other than matched sibling donor, and busulfex > 9 mg/kg were affecting factors for development of VOD/SOS. For severe to very severe VOD/SOS, history of pre-HCT liver dysfunction was an additionally affecting factor. Allogeneic-HCT using ursodiol and intravenous prophylaxis was considered safe without significant bleeding complications and should be evaluated in future clinical trials. For those with high-risk of VOD/SOS, early intervention and management is important.

We assessed the impact of donor type on long-term outcomes of allogeneic hematopoietic cell transplantation (HCT) in 440 consecutive adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1), particularly focusing on the donor type-specific difference in graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS). Donor sources were matched sibling donor (MSD; n = 199), matched unrelated donor (MUD; n = 110), 1-allele-mismatched unrelated donor (1-MMUD; n = 83), and cord blood (CB; n = 48). Cumulative incidence of severe chronic GVHD was 14.8% for MSD-HCT, 30.1% for MUD-HCT, 9.6% for 1-MMUD-HCT, and 4.2% for CBT, respectively (P

The recent improvements in the outcomes of severe aplastic anemia (SAA) patients who received allogeneic stem cell transplantation (SCT) from unrelated donors (URD) suggest the possibility of its alternative first-line treatment. To address this issue, results of adult SAA patients receiving allogeneic SCT were compared between the following three donor-type groups: 8/8–matched sibling (MSD; n = 153), 8/8 well-matched unrelated (WM-URD; n = 72), and 6–7/8 partially matched unrelated (PM-URD; n = 33). Proportion of patients who experienced immunosuppressive treatment failures was significantly higher in the URD groups than in the MSD group (P

Data regarding the optimal approach for second allogeneic hematopoietic stem cell transplantation (HSCT) after graft failure (GF) in acquired severe aplastic anemia (SAA) are still limited and heterogeneous. We examined 24 patients who underwent second HLA-matched sibling donor (MSD) peripheral blood HSCT for GF. The reconditioning regimen (TNI-750/ATG) consisted of a single dose of total nodal irradiation (TNI, 750 cGy) and antithymocyte globulin (ATG; Thymoglobulin®, 1.25 mg/kg/day for 3 days). All but one patient achieved successful engraftment of neutrophils (median 12 days, range 5–21) and platelets (median 15 days, range 9–316). Two patients with subsequent secondary GF achieved successful engraftment after a third HSCT from the same MSD. After a median follow-up of 57.4 months (range, 11.2–155.2), the 5-year overall survival and failure-free survival were 95.7% (95% confidence interval [CI] 87.7–100%) and 87.5% (95% CI 75.2–100%), respectively. One patient developed grade II acute graft-versus-host disease (GVHD), and the 2-year cumulative incidence of chronic GVHD was 23.5% (95% CI 8.1–43.5%). This study demonstrated successful outcomes following a second MSD HSCT in SAA after GF, and the results suggest TNI-750/ATG is a feasible reconditioning option. Future studies with larger cohorts will validate our results.

Hemolytic anemia with null PKLR mutations identified using whole exome sequencing and cured by hematopoietic stem cell transplantation combined with splenectomy

Low bone mineral density in adolescents with leukemia after hematopoietic stem cell transplantation: prolonged steroid therapy for GvHD and endocrinopathy after hematopoietic stem cell transplantation might be major concerns?

PBSCs are increasingly being chosen as the mode of donation among unrelated donors. Pediatric patients, in particular, may receive very high CD34(+) and CD3(+) doses during unrelated PBSCT. In this work, we analyzed survival and GVHD outcomes in a cohort of 81 children who received unrelated PBSCT with uniform antithymocyte globulin (ATG)-based in vivo T-cell depletion for treatment of hematologic malignancy, with emphasis on the impact of cell dose on transplant outcomes. EFS was 61.5±5.6%, with higher CD34(+) dose (>10.0 × 10(6)/kg) and lower patient risk status predicting improved survival in multivariate study. Cumulative incidence of relapse was 30.2±5.2%; a low CD34(+) dose was the only significant factor for relapse. Neither CD34(+) nor CD3(+) dose was a significant determinant of acute or chronic GVHD. Importance of CD34(+) dose was reaffirmed in a subcohort of younger patients who received greater median cell doses than the overall cohort. In summary, for children who received unrelated PBSCT with ATG-based T-cell depletion for treatment of hematologic malignancy, the CD34(+) dose was the most important factor for relapse and EFS, and neither the CD34(+) nor the CD3(+) dose influenced incidence of acute or chronic GVHD.

The objective of this study was to evaluate the efficacy and safety of micafungin for the prevention of invasive fungal infection (IFI) during the neutropenic phase of allogeneic hematopoietic SCT (allo-HSCT) in children and adolescents. This was a prospective, multicenter, open-label, single-arm study. Micafungin was administered i.v. at a dose of 1 mg/kg/day (max 50 mg) from the beginning of conditioning until neutrophil engraftment. Treatment success was defined as the absence of proven, probable, possible or suspected IFI through to 4 weeks after therapy. From April 2010 to December 2011, 155 patients were enrolled from 11 institutions in Korea, and 147 patients were analyzed. Of the 147 patients, 121 (82.3%) completed the protocol without premature interruption. Of the 132 patients in whom micafungin efficacy could be evaluated, treatment success was achieved in 119 patients (90.2%). There was no proven fungal infection in any patient. The number of patients with probable, possible and suspected IFI was two, two and nine, respectively. Thirty-five patients (23.8%) experienced 109 adverse events (AEs) possibly related to micafungin. No patients experienced grade IV AEs. Two patients (1.4%) discontinued micafungin administration due to adverse effects. None of the deaths were related to the study drug.