Outcomes after Second Hematopoietic Cell Transplantation in Children and Young Adults with Relapsed Acute Leukemia.

Children with acute leukemia who relapse after hematopoietic cell transplantation (HCT) have few therapeutic options. We studied 251 children and young adults with acute myelogenous or lymphoblastic leukemia who underwent a second HCT for relapse after their first HCT. The median age at second HCT was 11 years, and the median interval between first and second HCT was 17 months. Most of the patients (n = 187; 75%) were in remission, received a myeloablative conditioning regimen (n = 157; 63%), and underwent unrelated donor HCT (n = 230; 92%). The 2-year probability of leukemia-free survival (LFS) was 33% after transplantation in patients in remission, compared with 19% after transplantation in patients not in remission (P = .02). The corresponding 8-year probabilities were 24% and 10% (P = .003). A higher rate of relapse contributed to the difference in LFS. The 2-year probability of relapse after transplantation was 42% in patients in remission and 56% in those in relapse (P = .05). The corresponding 8-year probabilities were 49% and 64% (P = .04). These data extend the findings of others showing that patients with a low disease burden are more likely to benefit from a second transplantation. Late relapse led to a 10% decrement in LFS beyond the second year after second HCT. This differs from first HCT, in which most relapses occur within 2 years after HCT.

Sinusoidal Obstruction Syndrome During Maintenance Therapy for Acute Lymphoblastic Leukemia With 6-Mercaptopurine and Methotrexate: A Pediatric Case Report.

We report a case of a child with pre-B cell acute lymphoblastic leukemia undergoing maintenance chemotherapy with 6-mercaptopurine and methotrexate (MTX) who developed sinusoidal obstruction syndrome after being treated with ciprofloxacin for BK viremia. This case represents a rare complication of maintenance therapy with MTX and 6-mercaptopurine, and suggests a drug interaction between ciprofloxacin and MTX.

Neutrophil function in children following allogeneic hematopoietic stem cell transplant.

HSCT is a lifesaving procedure for children with malignant and non-malignant conditions. The conditioning regimen renders the patient severely immunocompromised and recovery starts with neutrophil (PMN) engraftment. We hypothesize that children demonstrate minimal PMN dysfunction at engraftment and beyond, which is influenced by the stem cell source and the conditioning regimen. Peripheral blood was serially collected from children at 1 to 12 months following allogeneic HSCT. PMN superoxide (O2-) production, degranulation (elastase), CD11b surface expression, and phagocytosis were assessed. Twenty-five patients, mean age of 10.5 yr with 65% males, comprised the study and transplant types included: 14 unrelated cord blood stem cells (cords), seven matched related bone marrow donors, three matched unrelated bone marrow donors, and one peripheral blood progenitor cells. Engraftment occurred at 24 days. There were no significant differences between controls and patients in PMN O2- production, phagocytosis, CD11b surface expression, and total PMN elastase. Elastase release was significantly decreased <6 months vs. controls (p < 0.05) and showed normalization by six months for cords only. The conditioning regimen did not affect PMN function. PMN function returns with engraftment, save elastase release, which occurs later related to the graft source utilized, and its clinical significance is unknown.

Hb Grand Junction (HBB: c.348_349delinsG; p.His117IlefsX42): a new hyperunstable hemoglobin variant.

Hyperunstable hemoglobinopathy (HUH) [dominantly inherited ß-thalassemia (ß-thal)] is a relatively rare form of congenital hemolytic anemia in which mutations occur in the genes encoding for α and ß chains, or both chains of the hemoglobin (Hb) molecule. We describe two Hispanic adolescents with a new unstable Hb variant (HBB: c.348_349delinsG; p.His117IlefsX42), resulting from a frameshift mutation at codons 115/116 of the ß-globin gene. Both patients also have a 3.7 kb deletion on one α gene, leading to a decreased imbalance between α and ß chain formation, and subsequently a milder phenotype than that seen in other hyperunstable Hb variants.