ABSTRACT
Hematopoietic stem cell transplantation (HSCT) remains the only curative option for most patients with juvenile myelomonocytic leukemia (JMML). However, persistent disease and relapse rates after transplant range from 26% to 58%. We report the successful use of second HSCT after preparation with mitoxantrone and cytosine arabinoside (Ara-C) for patients with refractory or recurrent disease. Between 1993 and 2006, 5 children who underwent HSCT at our institution as initial therapy for JMML had persistent disease or relapsed. Pre-HSCT conditioning varied and donors were either HLA-matched siblings (n=2) or matched unrelated donors (n=3). After initial HSCT, they subsequently received high-dose Ara-C (3 g/m IV) every 12 hours on days -8 through -3 and mitoxantrone (10 mg/m/d IV) on days -8, -7, -6 followed by second HSCT from their original donors. All 5 patients are alive at 88, 179, 199, 234, and 246 months with no evidence of JMML, no significant toxicity, and 100% donor chimera as determined by PCR short-tandem repeat analysis. Our experience supports second transplant utilizing high-dose Ara-C and mitoxantrone in children with JMML who do not respond or relapse after first transplant.
Subject(s)
Cytarabine/administration & dosage , Hematopoietic Stem Cell Transplantation , Leukemia, Myelomonocytic, Juvenile/drug therapy , Leukemia, Myelomonocytic, Juvenile/therapy , Mitoxantrone/administration & dosage , Antimetabolites, Antineoplastic/administration & dosage , Child , Child, Preschool , Combined Modality Therapy , Disease-Free Survival , Humans , Infant , Male , Recurrence , Retreatment , Tissue Donors , Transplantation Chimera , Transplantation Conditioning/methods , Transplantation, HomologousABSTRACT
A now 10-year-old Laotian female was delivered at 30-week gestation by cesarean section because of severe hydrops. Fetal blood sampling revealed homozygous α-thalassemia. After immediate resuscitation, the infant was supported with frequent red cell transfusions. At 44 months of age, she received a 5 of 6 human leukocyte antigen-matched unrelated cord blood transplantation. She was treated with phlebotomy and chelation therapy with Deferasirox for correction of hemosiderosis and has been transfusion-independent since 41 days after transplant. She is currently 6 years after transplantation with stable, 100% donor engraftment, resolved iron overload, and normal growth and development.
Subject(s)
Cord Blood Stem Cell Transplantation , Homozygote , alpha-Thalassemia/genetics , alpha-Thalassemia/therapy , Blood Transfusion , Chelation Therapy , Child , Female , Humans , Iron Overload/etiology , Iron Overload/therapy , Phlebotomy , Treatment Outcome , alpha-Thalassemia/complicationsABSTRACT
Normalized glomerular filtration rate (nGFR) <60 mL/min/1.73 m(2) often precludes hematopoietic stem cell transplant (HSCT) in pediatric patients. Three patients with nGFR < 60 mL/min/1.73 m(2) enrolled on an institutional phase I trial of HSCT preparative therapy for advanced and recurrent solid tumors with escalating melphalan, ranging from 135 to 180 mg/m(2), thiotepa (600 mg/m(2)), and vincristine (2 mg/m(2)). An additional patient with low nGFR was treated with the same preparative therapy. None of the patients developed acute renal failure, excess toxicities during HSCT or delayed engraftment. These cases demonstrate that it is feasible and safe to perform HSCT in pediatric patients with low nGFR using melphalan- and thiotepa-based preparative therapy.
Subject(s)
Glomerular Filtration Rate/physiology , Hematopoietic Stem Cell Transplantation , Kidney Neoplasms/therapy , Melphalan/therapeutic use , Neuroblastoma/therapy , Thiotepa/therapeutic use , Wilms Tumor/therapy , Antineoplastic Agents, Alkylating/therapeutic use , Child, Preschool , Combined Modality Therapy , Drug Therapy, Combination , Female , Humans , Infant , Kidney Neoplasms/physiopathology , Neuroblastoma/physiopathology , Transplantation, Autologous , Treatment Outcome , Wilms Tumor/physiopathologyABSTRACT
OBJECTIVES: To study the efficacy of hematopoietic stem cell transplantation (HCT) for ameliorating the clinical manifestations of alpha-mannosidosis. STUDY DESIGN: Four patients with alpha-mannosidosis underwent allogeneic HCT at the University of Minnesota. Diagnosis was established by assay of leukocyte alpha-mannosidase activity level. Physical features, donor engraftment, leukocyte alpha-mannosidase activity, neuropsychologic function, and hearing were monitored before and after transplantation, with follow-up ranging from 1 to 6 years. RESULTS: All 4 patients showed slowing of their neurocognitive development and sensorineural hearing loss before HCT. All patients are alive, with normalization of leukocyte enzyme activity after HCT. Intellectual function has stabilized, with improvement in adaptive skills and verbal memory function in 3 of 4 patients. Hearing has improved to normal or near normal for speech frequencies in 3 patients. No new skeletal abnormalities have developed. CONCLUSIONS: HCT can halt the progressive cognitive loss in patients with alpha-mannosidosis. Early diagnosis and treatment with HCT is critical for optimal results.
