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Biomedical subjects

B Camitta

Publications and source records attributed to B Camitta.

67 records · Page 4Linked to original sources

Intensive retreatment of childhood acute lymphoblastic leukemia in first bone marrow relapse. A Pediatric Oncology Group Study.

We devised a plan of intensive chemotherapy to address the problem of inadequate results of treatment in children with acute lymphoblastic leukemia in first bone marrow relapse. Immediately after remission was induced with four conventional drugs, a two-week intensification course of teniposide and cytarabine was given to eradicate subclinical leukemia. Patients in remission were then treated for two years with rapid rotation of pairs of drugs that were not cross-resistant and periodic courses of the same agents used to induce remission. A second complete remission was induced in 31 of the 39 patients in whom response to chemotherapy could be assessed. The probability of maintaining bone marrow remission in these patients for one year was 0.38 +/- 0.19 (95 percent confidence interval); the two-year probability was 0.29 +/- 0.17. Seven patients completed the treatment program, five of whom have been in continuous second complete remission 17 to 20 months after the cessation of therapy. Children whose initial bone marrow remission lasted less than 18 months had significantly poorer responses to retreatment than did those with a longer first remission (P = 0.004). Intensive chemotherapy, as described here, may save half of the children with acute lymphoblastic leukemia in whom bone marrow relapse occurs after a relatively long initial remission.

Adolescent↗

Bone marrow transplantation for severe aplastic anemia using a phenotypically HLA-identical, SB-compatible unrelated donor.

A three-year-old boy with severe aplastic anemia (HLA-A1,B8(Bw6), Cw7,DR3, MB2, MT2, SB4/A1,B8 (Bw6), Cw7,DR3,MB2,MT2,SB-) received a bone marrow transplant from a phenotypically HLA-identical, SB-compatible female unrelated donor. This donor was selected from eighteen HLA-A1,-B8,-blood donors after extended serotyping, mixed leukocyte culture testing and secondary proliferation assays with primed lymphocyte typing reagents specific for SB. Although patient cells proliferated well as responders in MLR, their stimulatory capability was greatly impaired. Because the patient had inherited the same serological HLA-D haplotype from each parent, it was concluded that a compatible unrelated donor must be homozygous for the same HLA-D antigens as the patient. This HLA-D homozygosity was demonstrated by the lack of MLR responses of both parents to stimulators from the donor. The SB typing results suggested SB compatibility because both the patient and the donor typed as SB4,-. Following bone marrow transplantation, there was rapid hematopoietic engraftment. The patient developed severe diarrhea caused by graft-versus-host disease of the gastrointestinal tract, which necessitated hyperalimentation. He is currently eighteen months posttransplant with full hematopoietic reconstitution and moderate chronic skin graft-versus-host disease.

Anemia, Aplastic↗

Antithoracic duct lymphocyte globulin therapy of severe aplastic anemia.

We performed a prospective randomized trial of antithoracic duct lymphocyte globulin (ATDLG), HLA-haploidentical marrow, and androgen (regimen ABA) versus androgen alone (concurrent STANDARD care controls) in 42 newly diagnosed individuals with severe aplastic anemia. ABA patients also were matched with patients from our preceding study (historical STANDARD care controls). Supportive care and pretreatment patient characteristics were the same in all groups. By life table analysis, 76% of patients receiving ABA are alive at 2 yr compared to 31% of the concurrent control group (p less than 0.002 versus ABA) and 19% of the historical controls (p less than 0.0001 versus ABA) given STANDARD care. ABA patients had greater hematologic improvement than either control group (p less than 0.001). However, improvement with ABA was often incomplete. Toxicity of ATDLG was considerable but manageable. Further studies to determine the mechanism of action and active component(s) of ABA are indicated.

Androgens↗

Bone marrow and extramedullary variations of cell membrane antigen expression in childhood lymphoid neoplasias at relapse.

To increase our knowledge of the pathogenesis of tumour recurrence, cell membrane phenotypes were determined on bone marrow and extramedullary tumour cells at diagnosis and at relapse in 24 children with lymphoid malignancies. There were 19 patients with acute lymphoblastic leukemia and five with non-Hodgkin's lymphoma. Membrane characteristics used for classification were E-rosetting, T antigen, surface immunoglobulin (sIg) and Ia antigen. Twelve patients were phenotyped as non-T, non-B, five as T-like and seven as B-like leukemia/lymphoma. Eighty-eight tissue samples were assayed for cell surface markers at the time of relapse(s). Lymphoblasts from 18 children (75%) demonstrated no variation in membrane marker expression. Six patients (25%) showed alteration of antigen expression on lymphoblasts obtained during relapses. This was manifested by loss of Ia antigen in two patients, loss of E-rosetting in one patient and loss of sIgD in one patient. Lymphoblasts from two patients, initially non-reactive with the four membrane markers utilized, expressed Ia antigen on subsequent relapses. Despite these variations no patient was categorized differently (i.e. T-like becoming non-T, non-B). Simultaneous lymphoblast phenotype determination from multiple body sites in 13 children showed no variation in marker analysis. A lymphoblast's phenotype remains stable throughout repeated relapses and is not influenced by relapse site in most children with lymphoid neoplasias. This information may be helpful in designing protocols where cytotoxic monoclonal antibodies are used as a treatment modality in patients with recurrent disease.

Antigens, Surface↗

Doxorubicin-vincristine therapy for Wilms' tumor: a pilot study.

Doxorubicin plus vincristine chemotherapy was given to 31 children following nephrectomy for Wilms' tumor. Radiation therapy was used as indicated. Disease-free survival by stage is: eight of nine patients (stage I), eight of nine (stage II), nine of ten (stage III), and two of three (stage IV). Median follow-up of survivors is 28 months (range, 2-67); for all but four patients, follow-up is greater than 12 months. Two of the three stage I-III failures occurred in children with unfavorable histologies; the third failure was due to fatal anthracycline cardiomyopathy. Lowering the maximal cumulative doxorubicin dose from 450 to 240 mg/m2 did not increase failures. Doxorubicin-vincristine appears to be effective chemotherapy for Wilms' tumor.

Adolescent↗

Doxorubicin cardiomyopathy in children with left-sided Wilms tumor.

Two children with Wilms tumor of the left kidney experienced severe anthracycline cardiomyopathy after irradiation to the tumor bed and conventional dosage of doxorubicin. The cardiomyopathy is attributed 1) to the fact that radiation fields for left Wilms tumor include the lower portion of the heart and 2) to the interaction of doxorubicin and irradiation on cardiac muscle. It is recommended that doxorubicin dosage be sharply restricted in children with Wilms tumor of the left kidney who receive postoperative irradiation.

Cardiomyopathies↗

Desacetyl vinblastine amide sulfate induced ineffective erythropoiesis.

Ineffective erythropoiesis occurred during desacetyl vinblastine amide sulfate (VDS) therapy of a patient with metastatic Ewing's sarcoma. The peripheral blood was characterized by anisocytosis, poikilocytosis and reticulocytopenia. Bone marrow showed megaloblastic red cell hyperplasia with nuclear fragmentation, binuclearity and abnormal metaphases. Radioiron incorporation into red cells was markedly decreased. Electron microscopy showed red cell surface changes previously called ropalocytosis. Normal erythropoiesis promptly resumed when VDS treatment was withheld. Although less common than leukopenia, red cell abnormalities are part of the spectrum of vinca alkaloid toxicity.

Adolescent↗

Successful use of multiagent immunosuppression in the bone marrow transplantation of sensitized patients.

Of 23 patients with severe aplastic anemia, 17 were sensitized to histocompatibility antigens of HLA-A, -B, and -D loci-identical potential sibling donors as determined by cell-mediated lysis (CML) assays in vitro. Antibody-dependent sensitization was detected in 3 patients, antibody-independent cellular sensitization in 11, and both in 3. Fourteen sensitized patients were transplanted after initial multiagent immunosuppression consisting of rabbit anti-human thymocyte serum, procarbazine, and cyclophosphamide, eleven with a CML-positive donor and three with a CML-negative donor. Engraftment was achieved in each of 13 patients who were evaluable, and only 2 ultimately rejected their marrow grafts, 1 with subsequent return of his own marrow function. Five patients without evidence in vitro of sensitization were transplanted after immunosuppression with cyclophosphamide alone; none of these rejected their grafts. These studies show that sensitized bone marrow transplant recipients can be successfully transplanted after optimal donor selection and multiagent immunosuppression.

Adolescent↗

The role of irradiation in central nervous system treatment and prophylaxis for acute lymphoblastic leukemia.

The results of central nervous system (CNS) treatment with craniocervical irradiation and intrathecal methotrexate in 117 children with ALL achieved at the Joint Center for Radiation Therapy. The Children's Hospital Medical Center, and The Sidney Farber Cancer Center are presented. A classification related to meningeal disease which correlated with prognosis is presented and the patients are analyzed within these groups. Of 80 patients classified in the most favorable groups (I and II), no child has suffered primary CNS relapse. Of the remaining 37 patients in less favorable groups (III, IV, and V), eight patients have experienced CNS relapse, five following or in conjunction with bone marrow relapse. The technical features of irradiation are reviewed and related to success of the treatment.

Adolescent↗

Detection of genetically determined histocompatibility antigen differences between HL-A identical and MLC nonreactive siblings.

Five patients with aplastic anemia were shown to be sensitized in vivo to the transplantation antigens of HL-A identical and MLC nonreactive sibling bone marrow transplantation donors. The sensitization in four cases were detected by antibody-dependent cell-mediated lysis (AICML) techniques, and in one case by antibody-dependent cell-mediated lysis (ADCML). In two cases the inherited nature of the sensitizing antigen was demonstrated, and in one case the inheritance of the antigen was shown by a family study to be independent of the HL-A and MLC loci. Maximal AICML was demonstrated in two cases at the time of bone marrow graft rejection. Successful transplants after immunosuppression with rabbit anti-thymocyte serum, procarbazine, and cyclophosphamide were performed in two patients, in whom sensitization was detected before transplantation.

Antibody Specificity↗