mercaptopurine and Graft-vs-Host-Disease

Topics: Apoptosis; Azathioprine; CD28 Antigens; Colitis, Ulcerative; Crohn Disease; Drug Therapy, Combination; Graft vs Host Disease; Humans; Immunosuppressive Agents; Mercaptopurine; Meta-Analysis as Topic; Nucleic Acids; Prodrugs; Randomized Controlled Trials as Topic; T-Lymphocytes

A 2-month-old girl presented for treatment with a diffuse rash, interstitial pneumonia, otorrhea, and lymphadenopathy. Skin biopsy confirmed Langerhans cell histocytosis by electron microscopy. After receiving multiple courses of chemotherapy, only marginal improvement was achieved, with progressive marrow and liver involvement. The decision was made to pursue a human leukocyte antigen-identical unrelated cord blood transplantation. Two years after transplant, the bone marrow was clear of Langerhans cell histocytosis and 100% donor engraftment. The poor prognosis of patients with an inadequate response to therapy and the presence of organ dysfunction (marrow and liver) substantiated the decision to pursue an unrelated cord blood transplantation.

Topics: Bone Marrow; Cladribine; Combined Modality Therapy; Cyclosporine; Cytarabine; Doxorubicin; Drug Therapy, Combination; Etoposide; Female; Fetal Blood; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Histiocytosis, Langerhans-Cell; Humans; Infant, Newborn; Mercaptopurine; Methotrexate; Methylprednisolone; Prednisone; Remission Induction; Transplantation, Homologous; Vinblastine

The authors describe a patient successfully treated with unrelated cord blood transplantation (CBT) for chemotherapy-resistant progressive Langerhans cell histiocytosis (LCH). An 8-month-old boy had LCH diagnosed based on the histologic examination of skin lesions. Despite intensive chemotherapy and immunotherapy, the disease was progressive, with organ dysfunction. He received unrelated CBT after a conditioning regimen consisting of total body irradiation, etoposide, and melphalan. He was in complete remission 12 months after the transplantation. The authors suggest that CBT could be considered in the treatment of patients with chemotherapy-resistant progressive LCH, especially if there are no available human leukocyte antigen-matched family donors.

Topics: Combined Modality Therapy; Cyclophosphamide; Cytarabine; Disease Progression; Doxorubicin; Drug Resistance; Drug Therapy, Combination; Etoposide; Fetal Blood; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Histiocytosis, Langerhans-Cell; Humans; Infant; Male; Mercaptopurine; Methotrexate; Methylprednisolone; Mitoxantrone; Prednisolone; Remission Induction; Transplantation Conditioning; Transplantation, Homologous; Vincristine

Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Infant; Leukemia, Myelomonocytic, Juvenile; Mercaptopurine; Transplantation, Homologous

Graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT), but membranous glomerulopathy (MG) has rarely been described as a manifestation of chronic GVHD. We report two cases of MG in children who underwent allogeneic HSCT. The clinical findings were characterized by edema of the lower extremities and nephrotic proteinuria in one case and hypertension, hematuria and edema with non-nephrotic proteinuria in the other one. Renal biopsy was consistent with MG and appropriate immunosuppressive therapy was prescribed. Both patients achieved complete remission and are alive without renal disease 4 and 2 years after the diagnosis of MG. The normal levels of albumin and non-nephrotic proteinuria in one of the two cases raise the question of whether the real incidence of MG after HSCT is underestimated. Therefore, we strongly suggest regular urine analysis during the follow-up of children undergoing HSCT in order to diagnose MG early.

Topics: Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Daunorubicin; Edema; Glomerulonephritis, Membranous; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Methotrexate; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Remission Induction; Transplantation Conditioning; Transplantation, Homologous; Vincristine

The authors describe a young boy with juvenile myelomonocytic leukemia (JMML) who relapsed 45 days after HLA and killer immunoglobulin-like receptor (KIR) mismatched unrelated donor bone marrow transplant (MMUD-BMT) and subsequently developed life-threatening graft-versus-host disease (GvHD). Treatment with 6-mercaptopurine (6-MP) appeared to control severe GvHD and possibly prevented recurrence of leukemic relapse.

Topics: Antimetabolites, Antineoplastic; Busulfan; Cyclophosphamide; Graft vs Host Disease; Graft vs Leukemia Effect; Hematopoietic Stem Cell Transplantation; Histocompatibility; HLA-B Antigens; HLA-B52 Antigen; HLA-C Antigens; Humans; Infant; Leukemia, Myelomonocytic, Acute; Male; Melphalan; Mercaptopurine; Receptors, Immunologic; Receptors, KIR; Remission Induction; Secondary Prevention; Transplantation Conditioning; Transplantation, Homologous

Aims of this study were to verify whether reduction in transplant-related mortality (TRM) of children with acute lymphoblastic leukemia (ALL) in second complete remission (CR) given allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated volunteers has occurred over time and to investigate the role of other variables on the probabilities of relapse, TRM and event-free survival (EFS). We compared results obtained in 26 children given HSCT before January 1998 with those of 37 patients transplanted beyond that date. In all donor-recipient pairs, histocompatibility was determined by serology for HLA-A and -B antigens and by high-resolution DNA typing for DRB1 antigen. High-resolution molecular typing of HLA class I antigens was employed in 20 of the 37 children transplanted more recently. Probability of both acute and chronic GVHD was comparable in the two groups of patients. In multivariate analysis, children transplanted before January 1998, those with T-lineage ALL and those experiencing grade II-IV acute GVHD had a higher relative risk of TRM at 6 months after transplantation. Relapse rate was unfavorably affected by a time interval between diagnosis and relapse <30 months. The 2-year probability of EFS for children transplanted before and after 1 January 1998 was 27% (10-44) and 58% (42-75), respectively (P = 0.02), this difference remaining significant in multivariate analysis. EFS of unrelated donor HSCT in children with ALL in second CR has improved in the last few years, mainly due to a decreased TRM. This information is of value for counseling of patients with relapsed ALL.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Disease-Free Survival; DNA, Neoplasm; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; HLA-A Antigens; HLA-B Antigens; HLA-DR Antigens; HLA-DRB1 Chains; Humans; Infant; Living Donors; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Registries; Remission Induction; Survival Rate; Time Factors; Transplantation, Homologous; Treatment Outcome; Vincristine

The early toxicity, incidence of graft-versus-host disease (GVHD) and long-term follow-up were evaluated in two children with Down syndrome (DS) treated for acute lymphoblastic leukemia (ALL) in second complete remission by HLA-matched sibling allogeneic bone marrow transplantation (BMT). Preparative conditioning therapy consisted of cytosine arabinoside (Ara-C) and fractionated total body irradiation (F-TBI) and GVHD prophylaxis of cyclosporin A. The conditioning regimen was well tolerated, the only acute complication being mild mucositis. Engraftment (polymorphonuclear cells >500/microliter) was documented by day +17 in both patients. One child remains in continuous complete remission, without medical problems, 60 months after BMT. The second patient died from complications associated with chronic GVHD 21 months following BMT. Ara-C and F-TBI is a well-tolerated preparative regimen for children with DS undergoing allogeneic BMT.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Child, Preschool; Combined Modality Therapy; Cranial Irradiation; Cytarabine; Daunorubicin; Down Syndrome; Fatal Outcome; Graft vs Host Disease; Humans; Male; Mercaptopurine; Methotrexate; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Salvage Therapy; Transplantation, Homologous; Vincristine; Whole-Body Irradiation

Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cytarabine; Daunorubicin; Female; Graft vs Host Disease; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Platelet Transfusion; Prednisolone; Transfusion Reaction

Topics: Animals; Antibodies; Cyclophosphamide; Female; Graft vs Host Disease; Hydrocortisone; Immunoglobulins; Injections, Intraperitoneal; Mechlorethamine; Mercaptopurine; Methotrexate; Mice; Skin Transplantation; Time Factors; Transplantation Immunology; Transplantation, Homologous

Topics: Adrenal Cortex Hormones; Animals; Bone Marrow Diseases; Dactinomycin; Dogs; Drug Synergism; Gastrointestinal Diseases; Graft vs Host Disease; Graft vs Host Reaction; Humans; Immunosuppressive Agents; Infections; Mercaptopurine; Rabbits; Transplantation, Homologous

Topics: Age Factors; Aminopterin; Animals; Antineoplastic Agents; Busulfan; Chlorambucil; Cyclophosphamide; Dactinomycin; Drug Tolerance; Graft vs Host Disease; Immunosuppressive Agents; Leukemia; Melphalan; Mercaptopurine; Methotrexate; Mice; Plants, Medicinal; Plants, Toxic; Podophyllin; Podophyllum; Skin Transplantation; Thioguanine; Transplantation, Homologous

Topics: Aminopterin; Animals; Busulfan; Cyclophosphamide; Dactinomycin; Graft vs Host Disease; Immunosuppressive Agents; Mercaptopurine; Mice; Models, Theoretical; Spleen; Transplantation Immunology

Topics: Animals; Antigens; Cachexia; Graft vs Host Disease; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Mice; Pharmacology; Prednisone; Radiation Effects; Research; Spleen; Transplantation Immunology