Systemic mastocytosis in a child with t(8;21) acute myeloid leukemia

Mastocytosis is primarily limited to the cutaneous variant in pediatric patients. Systemic mastocytosis (SM) has been associated with t(8;21) acute myeloid leukemia (AML) in adults. We provide the first report of a child with t(8;21) AML, diagnosed with asymptomatic SM following four cycles of chemotherapy. Unlike most adults with SM/AML, she was not found to have a c-KIT (D816V) mutation. SM persisted in the bone marrow after completion of chemotherapy, and her AML relapsed 9 months off-treatment. Although she achieved a second remission, mastocytosis persists in the marrow. Pediatric patients with t(8;21) AML/SM may represent a high-risk group despite favorable cytogenetics.     

Allogeneic hematopoietic stem cell transplantation in congenital disorders: A single‐center experience

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is the treatment of choice for a variety of congenital disorders. We report the experience of children affected by congenital diseases other than bone marrow failure syndromes who received allo‐HSCT over a period of 25 years at G. Gaslini Paediatric Research Institute. HSCTs were performed in 57 children with congenital diseases (25 with congenital immunodeficiencies, 10 with severe combined immunodeficiencies, and 22 with metabolic diseases). Overall survival rate at 3 years in the whole group of patients was 76.9%, with a trend in favor of better outcome in children with metabolic diseases and in those who received cord blood cells (85.9%) vs bone marrow cells (72.4%).     

Unexpected acute renal injury after high‐dose etoposide phosphate and total body irradiation in children undergoing hematopoietic stem cell transplantation

High‐dose etoposide phosphate, a water‐soluble prodrug of etoposide, may be used after total body irradiation (TBI) in pediatric allogeneic bone marrow transplantation for lymphoblastic leukemia. In a retrospective study of 21 children treated at the Nancy University Hospital (2000–2014), we identified unprecedentedly an unexpectedly high incidence (57%) of acute renal injury following etoposide phosphate infusion. Patients who developed renal function impairment experienced more severe mucositis but had outcomes similar to those who did not. No risk factors were identified. We speculate that the etoposide phosphate diluent, dextran 40, may have been the causative agent in these post‐TBI renal toxicity cases.     

Hematopoietic stem cell transplantation without in vivo T‐cell depletion for pediatric aplastic anemia: A single‐center experience

For young patients, HLA‐MRD HSCT is the first‐line treatment of SAA. However, due to China's birth control policy, few patients could find suitable sibling donors and HLA‐MUD. More and more transplantation centers have used Haplo‐D as the donor source for young adult and pediatric patients. However, studies with larger amount of pediatric patients are rare. We retrospectively analyzed the data of children with AA who were treated with allogeneic HSCT and compared the therapeutic efficacy of Haplo‐HSCT and MRD/MUD group. A total of 62 patients were enrolled. Implantation was successfully performed in 58 patients. There was no significant difference in the time for reconstruction of hematopoietic function between patients in the two groups. Thirty‐two had grade I‐IV aGVHD with incidence of 51.61%. The incidence of aGVHD was 79.41% for patients in the Haplo‐HSCT, significantly higher than that of 17.86% for patients in the MRD/MUD group (P < .01). However, the incidence of cGVHD was not significantly different between patients in the two groups (26.47% vs 10.71%, P = .09), the incidence of CMV infection was 28.57% and 52.94% for patients in the MRD/MUD and Haplo group, respectively, showing no significant difference (P = .053). The incidence of EBV infection was 47.06% for patients in the Haplo group and 28.57% for patients in the MRD/MUD group, showing no significant difference (P = .11). However, the 3‐ and 5‐year cumulative OS and FFS rates showed statistically significant difference in the two groups, P = .012 and .045, respectively. Compared to Haplo‐HSCT, MRD/MUD is more economic. In this study, we achieved good Haplo transplantation results. The incidences of cGVHD and CMV/EBV were not significantly different between Haplo group and MRD/MUD group. Although OS and FFS of the Haplo group were not as good as those of the MRD/MUD group, it is still acceptable as an alternative treatment under emergency.     

Acute graft‐versus‐host disease in pediatric allogeneic hematopoietic stem cell transplantation. Single‐center experience during 10 yr

a‐GvHD may complicate allogeneic HSCT. In this retrospective single‐center study, we evaluated incidence and risk factors of a‐GvHD in 197 consecutive allogeneic pediatric HSCTs applying Glucksberg and NIH a‐GvHD classifications. Among 179 eligible transplants, the cumulative incidence of grade 0–I a‐GvHD was 48% and grade II–IV was 52%. None of the considered variables significantly influenced the incidence of grade II–IV a‐GvHD. Malignancy and myeloablation were associated with an increased risk of classic a‐GvHD (p < 0.01). Seventy‐two percentage of children are alive, with a significant difference in OS and TRM between grade 0 and I vs. grade II and IV a‐GvHD; this observation was reproduced in the non‐malignant setting, while only a disparity in TRM was evidenced in children with malignancy. In our experience, the incidence of a‐GvHD was similar, regardless of donor type. Myeloablation and malignant disease represented the only risk factors for classic a‐GvHD. Our results highlight the need for a better prevention of this complication in the non‐malignant setting.     

Detectable minimal residual disease before allogeneic hematopoietic stem cell transplantation predicts extremely poor prognosis in children with acute lymphoblastic leukemia

BACKGROUND: The level of minimal residual disease (MRD) prior to allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to be an independent prognostic factor for outcome of pediatric patients with high-risk acute lymphoblastic leukemia (ALL). Retrospective studies which used (semi-) quantitation of clone-specific immunoglobulin/T-cell receptor (Ig/TCR) rearrangements have documented the feasibility and practicality of this technique. This approach has also been disputed due to the occurrence of clonal evolution and generally high MRD levels prior to HSCT. PROCEDURE: In our prospective study, MRD before and after HSCT was monitored using quantitative real-time PCR in a cohort of 36 children with ALL consecutively transplanted in our center between VIII/2000 and VII/2004. RESULTS: In 25 of 36 patients, MRD level prior HSCT was assessed. Seventeen patients were classified as MRD-negative and eight were MRD-positive up to 9 x 10(-2). In MRD-positive subgroup, seven events (six relapses) occurred post-transplant in striking contrast to only one relapse in MRD-negative subgroup (event-free survival (EFS) log-rank P < 0.0001). MRD proved to be the only significant prognostic factor in a multivariate analysis (P < 0.0001). Adoptive immunotherapy including donor lymphocyte infusions in patients with adverse dynamics of MRD after HSCT had only limited and/or temporary effect. Clonal evolution did not present a problem precluding MRD monitoring in any of patients suffering a post-transplant relapse. CONCLUSIONS: We show that MRD quantitation using clonal Ig/TCR rearrangements successfully assesses the risk in pediatric ALL patients undergoing allogeneic HSCT. As our ability to treat detectable MRD levels after HSCT is very limited, alternative strategies for MRD-positive patients prior HSCT are necessary.     

Retrospective analysis of children with high‐risk acute myeloid leukemia who underwent allogeneic hematopoietic stem cell transplantation following complete remission with initial induction chemotherapy in the AML‐05 clinical trial

In the AML‐05 clinical trial conducted by the Japanese Pediatric Leukemia/Lymphoma Group from 2006 to 2010, children with high‐risk acute myeloid leukemia (HR AML) received allogeneic hematopoietic stem cell transplantation (allo‐HSCT) at first complete remission (CR1). The aim of this study was to investigate the impact of allo‐HSCT on the outcome of HR AML. Patients with either monosomy 7, 5q?, t(16;21), Ph1, FLT3‐ITD, or induction failure after the first course of chemotherapy were eligible for transplant. Of 53 children with HR AML, 51 received allo‐HSCT—45 in CR1, five in CR2, and one with non‐CR. t(8;21), t(9;11), and t(16;21) abnormalities were identified in eight, five, and four patients, respectively. The stem cell sources varied—bone marrow in 30 patients, peripheral blood in three, and cord blood in 18. The median follow‐up was 62 months. The overall survival (OS) rates at 3 years were 73% and 25% for patients who received transplant at CR1 and ≥CR2, respectively. Multivariable analysis showed that patients with chronic graft‐versus‐host disease (cGVHD) had better OS. This study supports that allo‐HSCT is a suitable treatment for HR AML in CR1. The favorable outcome associated with cGVHD indicates that a graft‐versus‐leukemia effect might be occurring.     

Infliximab for steroid refractory or dependent gastrointestinal acute graft‐versus‐host disease in children after allogeneic hematopoietic stem cell transplantation

Yang J, Cheuk DKL, Ha SY, Chiang AKS, Lee TL, Ho MHK, Chan GCF. Infliximab for steroid refractory or dependent gastrointestinal acute graft‐versus‐host disease in children after allogeneic hematopoietic stem cell transplantation. Abstract: aGVHD of the GI tract is common after allogeneic HSCT. Corticosteroids are the mainstay of treatment. Recent data suggest infliximab might be beneficial for steroid refractory aGVHD. We reviewed our experience in 10 pediatric patients who developed severe steroid refractory aGVHD (stage 3, n = 6; stage 4, n = 4), after an allogeneic matched unrelated HSCT for various hematological diseases (leukemia, n = 7; thalassemia, n = 3). The median age was 9.5 yr (range, 0.8–18.5 yr). All patients received 10 mg/kg infliximab weekly for 3–4 doses. Eight patients had CR and two had partial response. None of the patients developed therapy‐related adverse effects. All patients developed infections subsequently, which may or may not be related to infliximab. Five patients developed chronic GVHD (cGVHD) (four severe, one mild). Six patients died at 66–1451 days post‐transplant, from infection (n = 3), aGVHD (n = 1), lung cGVHD (n = 1), or idiopathic pneumonia (n = 1). Four patients were alive at 238–924 days post‐transplant, all of whom had an increase in BMI by six months post‐transplant. In conclusion, infliximab is well tolerated and appears effective in children with steroid refractory or dependent GI aGVHD. Infection is common and mortality remains high.     

The challenge of long‐term follow‐up of survivors of childhood acute leukemia after hematopoietic stem cell transplantation in resource‐limited countries: A single‐center report from Brazil

With the number of long‐term HSCT survivors steadily increasing, attention needs to be focused on the late complications and quality of life. We therefore analyzed the outcome of 101 pediatric patients (<18 years old at the time of HSCT) transplanted for acute leukemia between 1981 and 2015 at Complexo Hospital de Clínicas, Federal University of Paraná, Brazil, and who survived at least two years after HSCT. The median follow‐up was 5.9 years (2.0‐29.0); median age at follow‐up was 17.5 years (2.98‐39.0). The 5‐year cumulative incidence of relapse was 27.5% (95% CI 18.6%‐36.4%). Two‐year cumulative incidence of chronic GVHD was 21.8% (95% CI 13.7%‐29.8%). Of the 101 patients, 72 patients (71.3%) presented with late effects. Those surviving longer after HSCT experienced more complications. Patients who received TBI‐based regimen developed more late effects (P = .013) and more endocrinological complications (P = .024). Endocrinological complications were the most common late sequelae found in this study. For childhood survivors, quality of life was not influenced by age (at HSCT or at last visit), time from HSCT, gender, donor, or GVHD. For survivors that no longer were children, only age at last visit impacted financial domain measures, irrespective of gender, donor, or GVHD. The current study confirms the high burden late complications after pediatric HSCT have on the survivors and underlines the importance of extended follow‐up.     

Outcomes of children,adolescents, and young adults following allogeneic stem cell transplantation for secondary acute myeloid leukemia and myelodysplastic syndromes—The MD Anderson Cancer Center experience

We conducted a retrospective analysis of outcomes for children and young adults with sAML/sMDS who underwent HSCT at our institution. Thirty‐two patients (median age 20 years) with sAML (n=24) and sMDS (n=8) received HSCT between 1990 and 2013. The median time from sAML/sMDS diagnosis to HSCT was 4.1 months (range: 1.2‐27.2 months). The transplant regimens were primarily busulfan based (n=19). BM was the primary donor source (n=15). Eleven recipients were transplanted with residual disease. At a median follow‐up of 62.3 months (range: 0.4‐250.9 months), 14 patients had disease recurrence. Acute GVHD, grade III/IV, occurred in three patients. Causes of death were as follows: disease relapse (n=12), infection (n=2), pneumonia (n=1), pulmonary hemorrhage (n=1), acute GVHD (n=1), and graft failure (n=1). A PS of ≥90% at the time of HSCT had a significant impact on PFS (P=.02). Patients achieving pretransplant primary CR (n=8) and those with sMDS and RA (n=6) had prolonged PFS (P=.04). On multivariate analysis, shorter time to transplantation (≤6 months from diagnosis of sAML/sMDS) was associated with superior OS (P=.0018) and PFS (P=.0005).