melphalan and Leukemia--Myelomonocytic--Juvenile

We report the outcomes of 30 patients with juvenile myelomonocytic leukemia (JMML) who received unmanipulated hematopoietic stem cell transplantation (HSCT) with oral or intravenous busulfan, fludarabine, and melphalan between 2001 and 2011. Mutations in PTPN11 were detected in 15 patients. Six patients received human leukocyte antigen (HLA)-matched HSCT from related donors, and 24 patients received HSCT from alternative donors, including 13 HLA-mismatched donors. Primary engraftment failed in five patients, all of whom had received allografts from HLA-mismatched donors. HLA-mismatched HSCT resulted in poorer event-free survival than HLA-matched HSCT (28.8 vs. 70.6 %). Three patients died of transplantation-related causes, and eight patients experienced hematological relapse (including five patients who died due to disease progression). Eight patients received a second HSCT, and four of these patients have survived. The 5-year estimated overall survival for all patients was 72.4: 88.9 % for the patients without a mutation in PTPN11 (n = 10) and 58.3 % for the patients with a mutation in PTPN11 (n = 15) (P = 0.092). The conditioning regimen reported in the present study achieved hematological and clinical remission in >50 % of patients with JMML who received HSCT from alternative donors, and may also be effective for JMML patients with PTPN11 mutation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Busulfan; Child; Child, Preschool; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Infant; Infant, Newborn; Leukemia, Myelomonocytic, Juvenile; Male; Melphalan; Retreatment; Retrospective Studies; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vidarabine

Human Severe Combined Immunodeficiency (SCID) is a prenatal disorder of T lymphocyte development that depends on the expression of numerous genes. Juvenile myelomonocytic leukemia (JMML), previously known as juvenile chronic myeloid leukemia (JCML), is a rare, myelodysplastic/myeloproliferative disease typically presenting in early childhood.. Two cases are described of immunodeficiency disorders, both treated with chemotherapeutic drugs (Busulfan plus cyclophosphamide) before bone marrow transplantation. After treatment, these two different cases showed several similar oral lesions: microdontia, root alterations, numerous tooth ageneses, incomplete calcification, enamel hypoplasia, premature apexification and hypodontia. Both subjects underwent dental and orthodontic treatment. The first phase comprised orthopaedic treatment using a removable appliance (Interim-G®) followed by rapid palatal expansion; in the second phase patients underwent tooth extraction and were treated using fixed appliances for 19 and 26 months, respectively (mean 2 years) to obtain final alignment and maximum intercuspation. In the third and final phase, reconstruction of malformed teeth was completed, and implant-supported protheses were applied.. The difficulties of managing and treating these diseases are discussed, with particular focus on tooth anomalies and malocclusion disorders. Collaboration between dentist and paediatrician in dealing with patients with a variety of oral lesions and tooth anomalies is important in order to prevent any other possible tooth lesions and ensure correct jaw development.

Topics: Adolescent; Antineoplastic Agents, Alkylating; Bone Marrow Transplantation; Busulfan; Child; Cyclophosphamide; Humans; Leukemia, Myelomonocytic, Juvenile; Male; Malocclusion; Melphalan; Severe Combined Immunodeficiency; Tooth Abnormalities

A pilot study was undertaken using a myeloablative conditioning with fludarabine, busulfan, and melphalan to improve the outcome of HSCT in 10 children, aged six months to six yr, with JMML. All patients were conditioned with oral busulfan (560 mg/m(2)), fludarabine (120 mg/m(2)), and melphalan (180-210 mg/m(2)) prior to HSCT, and received stem cells from bone marrow in seven cases, and from cord blood in three cases. Engraftment was documented in eight patients, whereas graft failure occurred in two, one of whom had received HLA-mismatched cord blood and other had received bone marrow from HLA-mismatched mother. Three patients, including two in who graft failure had occurred, relapsed. Five patients developed acute GVHD and two developed chronic GVHD. Seven patients are alive and in remission 27-69 months after transplantation. Thus, our study showed that HSCT following conditioning with fludarabine, busulfan, and melphalan was well tolerated and appeared to be effective for JMML.

Topics: Administration, Oral; Busulfan; Child; Child, Preschool; Female; History, Ancient; Humans; Immunosuppressive Agents; Leukemia, Myelomonocytic, Juvenile; Male; Melphalan; Pilot Projects; Remission Induction; Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Homologous; Vidarabine