The relationship between regulatory T cells (Tregs) and acute graft-versus-host disease (GVHD) in clinical allogeneic bone marrow transplantation (BMT) recipients is not well established. We conducted a prospective analysis of peripheral blood Tregs as determined by the frequency of CD4+CD25hiFOXP3+ lymphocytes in 215 BMT patients. Autologous BMT patients (N=90) and allogeneic BMT patients without GVHD (N=65) had similar Treg frequencies, whereas allogeneic patients with GVHD (N=60) had Treg frequencies that were 40% less than those without GVHD. Treg frequencies decreased linearly with increasing grades of GVHD at onset and correlated with eventual maximum grade of GVHD (p<0.001). In addition, frequency of Tregs at onset of GVHD predicted the response to GVHD treatment (p=0.003). Patients with Treg frequencies less than the median had higher non-relapse mortality than patients with Tregs greater than the median, but experienced equivalent relapse mortality, resulting in an inferior survival at two years (38% vs. 63%, p=0.03). Treg frequency may therefore have important prognostic value as a biomarker of acute GVHD.

BackgroundAcute colonic pseudo-obstruction (ACPO) refers to dilatation of the colon and decreased bowel motility without evidence of mechanical obstruction. Neostigmine, an acetylcholinesterase inhibitor, has been used in patients in whom supportive therapy failed to resolve ACPO. Here, we report the results of administering neostigmine to treat ACPO in children with hematologic malignancies.MethodsBetween September 2005 and December 2009, 10 patients (8 male and 2 female) were diagnosed with ACPO at the Department of Pediatrics, Catholic University of Korea. Diagnosis of ACPO was based on typical clinical features as well as colonic dilatation found on abdominal CT imaging. Neostigmine was administered subcutaneously at a dosage of 0.01 mg/kg/dose (maximum 0.5 mg) twice daily for a maximum of 5 total doses. ACPO was determined to be responsive to neostigmine if the patient showed both stool passage and improvement of clinical symptoms.ResultsThe study group included 8 acute lymphoblastic leukemia patients, 1 patient with malignant lymphoma, and 1 patient with juvenile myelomonocytic leukemia. The median age at ACPO diagnosis was 8.5 years (range, 3-14). Overall, 8 patients (80%) showed therapeutic response to neostigmine at a median of 29 hours after the initial administration (range, 1-70). Two patients (20%) showed side effects of grade 2 or above, but none complained of cardiovascular symptoms that required treatment.ConclusionIn this study, ACPO was diagnosed most often in late-childhood ALL patients. Subcutaneous neostigmine can be used to effectively treat ACPO diagnosed in children with hematologic malignancies without major cardiovascular complications.

BackgroundAutoimmune cytopenia (AIC) is a rare complication of allogeneic hematopoietic cell transplantation (HCT). In this study, we reviewed the diagnosis, treatment and response to therapy for pediatric patients with post-HCT AIC at our institution.MethodsOf the 292 allogeneic HCTs performed from January, 2011 to December, 2015 at the Department of Pediatrics, The Catholic University of Korea, seven were complicated by post-HCT AIC, resulting in an incidence of 2.4%.ResultsAll seven patients with post-HCT AIC had received unrelated donor transplant. Six of seven patients had a major donor-recipient blood type mismatch. The subtypes of AIC were as follows: immune thrombocytopenia (ITP) 2, autoimmune hemolytic anemia (AIHA) 2, Evans syndrome 3. Median time from HCT to AIC diagnosis was 3.6 months. All but one patient responded to first line therapy of steroid±intravenous immunoglobulin (IVIG), but none achieved complete response (CR) with this treatment. After a median duration of treatment of 15.3 months, two patients with ITP achieved CR and five had partial response (PR) of AIC. Five patients were treated with rituximab, resulting in the following response: 2 CR, 2 PR, 1 no response (NR). Median time to response to rituximab was 26 days from first infusion. All patients are alive without event.ConclusionPost-HCT AIC is a rare complication that may not resolve despite prolonged therapy. Rapid initiation of second line agents including but not limited to B cell depleting treatment should be considered for those that fail to achieve CR with first line therapy.

In this single-institution study of Korean pediatric ALL patients, risk group based intensification with omission of cranial irradiation resulted in EFS comparable to previous studies, excellent survival of low- and standard-risk patients, and a low rate of CNS relapse.