Hepatic cirrhosis is a very rare complication of hematopoietic stem cell transplantation (SCT) and of neuroblastoma. We encountered two patients developing cirrhosis after SCT against neuroblastoma. A 6-year-old boy who had received allogeneic bone marrow transplantation developed cirrhosis 10 years after the SCT with the massive upper gastrointestinal hemorrhage. A 27-year-old man receiving allogeneic cord blood transplantation against recurrence of neuroblastoma, died of liver failure due to histological cirrhosis 1 year after the SCT. We could not detect the definite etiologic candidates of cirrhosis; however, careful monitoring appears warranted to avoid overlooking the onset and progression of cirrhosis after SCT.

Background. Therapy for relapsed or refractory (r/r) T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in children is challenging, and new treatment methods are needed. Previous studies have shown a promising response to the addition of nelarabine to chemotherapy for r/r T-ALL and T-LBL. Methods. We retrospectively analyzed the therapy of nelarabine in combination with etoposide, cyclophosphamide, and intrathecal therapy in eight pediatric patients with r/r T-ALL and T-LBL. The treatment regimen consisted of five consecutive days each of nelarabine (650mg/m 2/dose) and etoposide (100mg/m 2/dose)/cyclophosphamide (440mg/m 2/dose) separated by at least three days. Results. Five patients had T-ALL, and three patients had T-LBL. Of all patients, five achieved complete response, and the other three achieved partial response. All the patients underwent hematopoietic stem cell transplantation (HSCT) after two cycles of the treatment, except for one case with one course. Three patients who had previously received HSCT were treated with reduced-intensity conditioning regimens, including fludarabine, melphalan, and nelarabine; one of whom is still alive over five years after the second HSCT. Grade 2 neuropathy occurred in one patient, and other severe toxicities commonly associated with nelarabine were not observed during nelarabine-containing salvage therapy. With a median follow-up of 900 days for survivors, the 2-year overall survival and event-free survival rates were 60.0% and 36.5%, respectively. Conclusion. The addition of nelarabine to reinduction chemotherapy was useful for HSCT in remission and did not lead to excessive toxicity. In addition, a conditioning regimen including nelarabine appeared to be effective in previous HSCT patients.

Most cases of aplastic anemia (AA) complicated by nephrotic syndrome (NS) have been reported to be the effects of chronic graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). We describe a 16-year-old boy with AA with monosomy 7 who developed NS during immunosuppressive treatment for AA alone without HSCT. Recently, there appeared a report of MIRAGE syndrome caused by gain-of-function mutation of SAMD9 gene on chromosome 7 who developed NS. No such mutation was detected in our patient and thus the genetic factors leading to the complication of two diseases remain unknown at this time.

Background. One- or two-day intervals are generally inserted into scheduled conditioning regimens for allogeneic hematopoietic cell transplantation (HCT), primarily due to various social circumstances, such as unexpected natural adversities, abrupt deterioration of patient health, and delays in graft source arrival. We compared the clinical outcomes of patients with interrupted conditioning to those with ordinarily scheduled conditioning. Procedure. We retrospectively analyzed 83 patients (children and adolescents) with oncologic disease who underwent myeloablative conditioning with total body irradiation (TBI). Interruption of conditioning was defined as a regimen in which one or two vacant days (no chemotherapy drug administration or TBI) were added to the initially scheduled regimen. Results. Overall and event-free survival were similar between the scheduled conditioning group and the interrupted conditioning groups (P = 0.955, P = 0.908, respectively). Non-relapse mortality and relapse rates were similar between the groups (P = 0.923, P = 0.946, respectively). The engraftment rate was not affected by interruption (P = 1.000). In contrast, the incidence of grade II–IV acute graft-versus-host disease (GVHD) reached a marginally significant difference between the groups (31% vs. 11%; P = 0.083). Conditioning interruption was identified to be an independent risk factor for chronic GVHD by multivariate analysis (odds ratio: 3.72; 95% CI: 1.04–13.3; P = 0.043). Conclusion. Apart from the incidence of chronic GVHD, clinical outcomes were not affected by one- or two-day intervals during conditioning.

Few studies have investigated the association between severity of lymphopenia and clinical outcome during chemotherapy or hematopoietic stem cell transplantation (HSCT). We investigated this issue by retrospectively analyzing pediatric patients who received allogeneic-HSCT (allo-HSCT) using a newly developed parameter called the LD-index that combines both the duration and the intensity of lymphopenia. A total of 92 patients underwent allo-HSCT in our hospital from April 2007 to August 2019. The median age at HSCT was 10.3 years (range 0.4 – 28.1). The median LD-index was 9,285 (range 2,217 – 36,064). A significantly high association was observed between the LD-index and the incidence of chronic graft-versus-host disease (GvHD) (p = 0.0045). Analysis of predictive factors for chronic GvHD was carried out using univariate analysis. Lower LD-index, donor source and duration (days) of lymphopenia were found to be significant factors associated with chronic GvHD. Multivariate analysis, however, only identified an association between lower LD-index and increased incidence of chronic GvHD (p = 0.004). In conclusion, the duration and the intensity of lymphopenia after allo-HSCT have an effect on the development of chronic GvHD.

Background. Adolescents/young adults (AYAs) with acute lymphoblastic leukemia (ALL) are more likely to have chemotherapy-related complications than children. In addition, several reports have shown that infections account for most of the therapy-related mortality during cancer treatment in AYAs. Thus, we hypothesized that chemotherapy-induced myelosuppression is more severe in AYAs than in children, and the state of neutropenia was compared between children and AYAs using the D-index, a numerical value calculated from the duration and depth of neutropenia. Procedure. This study retrospectively analyzed 95 patients newly diagnosed with ALL at our institution between 2007 and 2019. Of these, 81 were children (< 15 years old) and 14 were AYAs (≥ 15 years old). The D-index and duration of neutropenia during induction chemotherapy for ALL were compared between children and AYAs. Results. The median D-index of children was significantly higher than that of AYAs (8,187 vs. 6,446, respectively, P = 0.017). Moreover, the median duration of neutropenia was also significantly longer in children than in AYAs (24.0 days vs. 11.5 days, respectively, P = 0.007). Conclusion. Contrary to our expectations, myelosuppressive toxicity during induction chemotherapy for ALL was more severe in children than in AYAs.