Matched-unrelated-donor bone marrow transplantation for children with leukemia.

BACKGROUND AND PURPOSE: This report describes the results of matched-unrelated-donor transplant for leukemia or myelodysplasia in the first 23 recipient children at a single medical center in Taiwan. METHODS: Between August 1994 and February 2003, 23 consecutive children with leukemia or myelodysplasia underwent matched-unrelated-donor bone marrow transplantation (BMT). The preparative regimen consisted of fractionated total body irradiation and cyclophosphamide in 6 patients; busulfan in combination with etoposide and cyclophosphamide in 4 patients who received cranial irradiation before transplantation; and busulfan and cyclophosphamide in 13 patients. RESULTS: Engraftment was achieved in 91.3% of cases. Acute graft-versus-host disease (GVHD) occurred in 18 of 21 patients who engrafted (85.7%). Event-free survival for all patients was 24.46 +/- 9.24%. The 12 children with standard-risk disease had better event-free survival than the 11 children with high-risk disease (46.88 +/- 15.03% vs 0%, p < or = 0.001). CONCLUSIONS: The major obstacles to successful matched-unrelated-donor BMT are acute GVHD, relapse and infection. Early transplantation and patient selection, prophylactic and therapeutic maneuvers for GVHD, as well as appropriate donor selection and virus prophylaxis may improve the results.     

Ureteral obstruction caused by L-asparaginase-induced pancreatitis in a child with acute lymphoblastic leukemia.

L-asparaginase, an effective antileukemia and antilymphoma agent, is toxic to many organ systems. We report a case of ureteral obstruction caused by L-asparaginase via the inflammatory complication of acute pancreatitis. The patient was an 11-year-old boy with acute lymphoblastic leukemia. Six days after completing a 4-week induction therapy containing 9 doses of L-asparaginase, severe left abdominal pain developed. Abdominal computed tomography showed phlegmon formation anterior to the pancreatic head and in the left posterior pararenal space. The strands of inflammatory soft tissues encased the upper third of the left ureter, causing left hydroureter and left hydronephrosis. The ureteral obstruction resolved after insertion of a double-J catheter that remained in place for 66 days. This case suggests that L-asparaginase may play a role in the pathogenesis of ureteral obstruction in children receiving chemotherapy.     

Inappropriately low reticulocytosis in severe malarial anemia correlates with suppression in the development of late erythroid precursors

Inappropriately low reticulocytosis may exacerbate malarial anemia, but the under-lying mechanism is not clear. In this study, naive and infected mice were treated with recombinant murine erythropoietin (EPO), and the upstream events of erythropoiesis affected by blood-stage Plasmodium chabaudi AS were investigated. Malaria infection, with or without EPO treatment, led to a suboptimal increase in TER119(+) erythroblasts compared with EPO-treated naive mice. Furthermore, a lower percentage of TER119(+) erythroblasts in infected mice were undergoing terminal differentiation to become mature hemoglobin-producing erythroblasts. The impaired maturation of erythroblasts during infection was associated with a shift in the transferrin receptor (CD71) expression from the TER119(+) population to B220(+) population. Moreover, the suboptimal increase in TER119(+) erythroblasts during infection coincided with a blunted proliferative response by splenocytes to EPO stimulation in vitro, although a high frequency of these splenocytes expressed EPO receptor (EPOR). Taken together, these data suggest that during malaria, EPO-induced proliferation of early EPOR-positive erythroid progenitors is suppressed, which may lead to a suboptimal generation of TER119(+) erythroblasts. The shift in CD71 expression may result in impaired terminal maturation of these erythroblasts. Thus, inadequate reticulocytosis during malaria is associated with suppressed proliferation, differentiation, and maturation of erythroid precursors.     

Epstein-Barr virus associated post-transplantation lymphoproliferative disorder with hemophagocytosis in a child with Wiskott-Aldrich syndrome

A 23-month-old boy with Wiskott-Aldrich syndrome (WAS) received human leukocyte antigen (HLA)-one locus mismatched, unmanipulated allogeneic bone marrow graft from his mother. An Epstein-Barr virus (EBV)-associated post-transplantation lymphoproliferative disorder (PTLD) of donor cell origin and hemophagocytosis syndrome with fever, lymphadenopathy, hepatosplenomegaly, seizures, involuntary movements and pancytopenia developed 52 days after transplantation. It was difficult to decide on the treatment strategy because the patient presented with B-cell hyperplasia that morphologically appeared malignant but was oligoclonal by heavy-chain analyses. Despite of donor leukocyte transfusion, low dose chemotherapy, and anti-B cell monoclonal antibody immunotherapy, the patient died 107 days after transplantation.     

A trend of improved survival of childhood hepatoblastoma treated with cisplatin and doxorubicin in Taiwanese children

Hepatoblastoma is the second most common childhood malignant hepatic tumor in Taiwan. Its prognosis used to be poor. We reviewed our cases in this decade to see if there has been any improvement of survival in our patients with hepatoblastoma. From 1988 to 2000, 19 patients with hepatoblastoma in this institution were included in the study. These patients clinical manifestations, laboratory and image studies, histological findings, treatment modalities and prognostic significance were analyzed. The mean age at diagnosis was 13.5 months, ranging from 0 to 4 years old (male:female =11:8). Abdominal distension was the most common symptom, and hepatomegaly was the most common physical finding. Laboratory abnormalities included elevated alpha-fetoprotein, thrombocytosis and abnormal liver function profiles. Treatment modalities included primary surgery with postoperative chemotherapy in three, chemotherapy only in four and preoperative chemotherapy plus surgery with or without postoperative chemotherapy in nine patients. The overall 2-year survival rate is 38.6%. The significant prognostic factors include patients compliance, resectability and chemotherapy protocol. The introduction of a new chemotherapy protocol designed by the International Society of Pediatric Oncology Study (SIOPEL) in 1994 improved the 2-year survival rate from 12.5 to 58.4% (P=0.01). In conclusion, the improved chemotherapy protocol enhances the survival rate of hepatoblastoma in Taiwanese children.     

Post-hepatitic aplastic anaemia in children in Taiwan, a hepatitis prevalent area

Aplastic anaemia is a rare but serious complication of hepatitis, and hepatitis is an unusual cause of aplastic anaemia in children in the West. However, the relative frequencies of acquired aplastic anaemia in children in Taiwan, a hepatitis prevalent area, differ from those in the West, in the very high frequency of post-hepatitic aplastic anaemia (23.9% of all cases of aplastic anaemia). This may account for the higher incidence of aplastic anaemia in children in Taiwan. Although the prognosis of post-hepatitic severe aplastic anaemia was very poor, the present study using bone marrow transplantation, antithymocyte (or antilymphocyte) globulin, high-dose methylprednisolone and cyclosporin, etc., has improved the response rate and the survival.     

Acute lymphoblastic leukemia occurring as a second malignant neoplasm in a child.

The effective treatment of childhood malignancies has increased the importance of early detection and treatment of second malignant neoplasms. Anticancer drugs may also be leukemogenic agents, by the same mechanisms that kill cancer cells. We report the case of a 10-year-old boy who had received radiotherapy and chemotherapy for the treatment of Ewing's sarcoma and developed acute lymphoblastic leukemia 22 months after the diagnosis of primary malignancy. Although chemotherapy is well known to potentiate the development of second acute nonlymphocytic leukemia, the pathogenic factors leading to second acute lymphoblastic leukemia remain obscure.     

Hematopoietic stem cell transplantation in Taiwanese children with primary immunodeficiency.

BACKGROUND AND PURPOSE: Since 1968 it has been known that hematopoietic stem cell transplantation (HSCT) can ameliorate primary immunodeficiencies, but data on the long-term efficacy of this treatment in Taiwan are limited. This study analyzed the outcome of HSCT and the immune reconstruction in 10 children with primary immunodeficiencies in Taiwan. METHODS: We retrospectively analyzed the outcome of HSCT in 10 children with primary immunodeficiencies between 1986 and 2002. The primary immunodeficiencies in these children included severe combined immunodeficiency (SCID) in 4, Wiskott-Aldrich syndrome (WAS) in 4, Chediak-Higashi syndrome (CHS) in 1, and leukocyte adhesion deficiency (LAD) in 1. The conditioning protocols included busulfan and cyclophosphamide in 2 patients with SCID, 3 patients with WAS, 1 patient with LAD and 1 patient with CHS. Anti-thymocyte globulin was given to only 1 patient with WAS and no conditioning therapy was given in 2 SCID patients. Graft-versus-host disease (GVHD) prophylaxis with cyclosporine (CsA) and methotrexate was prescribed in 6 children, CsA alone in 1, and CsA and T-cell depletion in 1. RESULTS: Six patients were cured and 1 improved during a follow-up period from 3.5 years to 13 years after transplantation. Three patients died of severe sepsis. Three patients developed acute GVHD, which was grade 2 in 2 patients, and grade 3 in 1. Veno-occlusive disease developed in 1 patient and chronic GVHD with contracture of joints in 1. CONCLUSIONS: Our results support the benefits of allo-HSCT in children with primary immunodeficiencies. However, HSCT should be performed as soon as possible before severe infection develops.