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Biomedical subjects

R Champlin

Publications and source records attributed to R Champlin.

At least 199 records · Page 11Linked to original sources
PubMed1990

Effect of recombinant human granulocyte-macrophage colony-stimulating factor administration on the lymphocyte subsets of patients with refractory aplastic anemia.

Human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was administered to 14 patients with refractory aplastic anemia (AA). The effect of rhGM-CSF therapy on the lymphocyte phenotype; on the proliferative responses to the mitogen phytohemagglutinin, Candida albicans, and tetanus toxoid antigens; and on the natural killer (NK) activity of the circulating lymphocytes was studied. Samples were collected before (baseline) and twice during the rhGM-CSF administration. The absolute number of circulating lymphocytes remained relatively constant during the first period, but experienced a significant increase (P less than .001) during the second period. The increase was most prominent in the B cells (P less than .001), but the T cells (P less than .016) also increased. Detailed investigation of lymphocyte subsets showed an increase of the markers CD38 (Leu17), HLA-DR, and the transferrin receptor throughout the treatment course giving evidence of lymphoid cell activation. The NK cell activity was suppressed (P less than .008) throughout the treatment. However, proliferative responses to phytohemagglutinin, Candida antigen, and tetanus toxoid were unaffected. Although the mechanism is not yet defined, GM-CSF does induce activation and increase in absolute lymphoid cell number, especially B cells, together with a decrease in NK cytotoxicity. The implication of these immune cell changes in relation to host resistance to microorganisms remains to be established.

ADP-ribosyl Cyclase↗
PubMed1990

Selective depletion of CD8+ T lymphocytes for prevention of graft-versus-host disease after allogeneic bone marrow transplantation.

The effects of selectively depleting CD8+ cells from donor bone marrow were assessed in 36 patients receiving transplantation from an HLA-identical sibling as treatment for leukemia. Donor bone marrow underwent ex vivo treatment using anti-Leu-2 monoclonal antibody and complement. Patients received cyclosporine post-transplant for 6 months. Thirty-three patients had initial engraftment. Three failed to have hematologic recovery, and one patient with initial engraftment had late graft failure. The actuarial incidence of grade greater than or equal to 2 acute graft-versus-host disease was 28% +/- 18% and was usually confined to the skin. Of 33 patients with engraftment, 32 were complete chimeras and one had mixed chimerism. The tempo of hematologic and immunologic recovery was comparable with that reported with transplantation of unmodified bone marrow, although CD4+ and CD8+ T cells recovered at comparable rates. The actuarial rate of leukemia relapse was 11% +/- 10%, occurring in three patients with acute leukemia but in none of 13 patients transplanted for chronic myelogenous leukemia. Actuarial survival was 57% +/- 17% at 2 years. These data indicate that after transplantation of marrow depleted of CD8+ cells, engraftment with prompt hematologic and immunologic recovery generally occurs, with a relatively low rate of acute graft-versus-host disease. Graft failure remains a problem despite retention of CD4+ cells within the donor marrow. The lack of leukemia relapse in patients with chronic myelogenous leukemia suggests retention of a graft-versus-leukemia effect, at least for this malignancy.

Adolescent↗
PubMed1990

Molecular relapse in chronic myelogenous leukemia patients after bone marrow transplantation detected by polymerase chain reaction.

Relapse of chronic myelogenous leukemia after bone marrow transplantation can be detected by using clinical, cytogenetic, or molecular tools. A modification of the polymerase chain reaction can be used in patients to detect low levels of the BCR-ABL-encoded mRNA transcript, a specific marker for chronic myelogenous leukemia. Early detection of relapse after bone marrow transplantation could potentially alter treatment decisions. We prospectively evaluated 19 patients for evidence of molecular relapse, cytogenetic relapse, and clinical relapse after bone marrow transplantation. We used the polymerase chain reaction to detect residual BCR-ABL mRNA in patients followed up to 45 months after treatment (median, 15 months; range, 6-45 months) and found 4 patients with BCR-ABL mRNA expression following bone marrow transplantation. In 2 patients BCR-ABL mRNA was detected in all samples, and both have developed cytogenetic relapse. In 1 patient BCR-ABL mRNA was detected transiently during the first month after transplant but was undetectable thereafter. The fourth patient had BCR-ABL mRNA 6 months after bone marrow transplantation but not in prior samples. Fifteen patients did not express detectable BCR-ABL mRNA. All 19 patients remain in clinical remission. In this prospective study of chronic myelogenous leukemia patients treated with bone marrow transplantation, molecular relapse preceded cytogenetic relapse in those patients who persistently express BCR-ABL mRNA. We recommend using standard clinical and cytogenetic testing to make patient care decisions until further follow-up determines the clinical outcome of those patients with residual BCR-ABL mRNA transcripts detected by polymerase chain reaction.

Base Sequence↗
PubMed1990

Postremission chemotherapy for adults with acute myelogenous leukemia: improved survival with high-dose cytarabine and daunorubicin consolidation treatment.

Results of postremission chemotherapy for adults with acute myelogenous leukemia (AML) were assessed in two sequential prospective studies involving similar induction therapy and two courses of intensive consolidation treatment. Fifty-six patients achieving remission on the acute leukemia protocol (ALP3) study received high-dose cytarabine and daunorubicin as course one and standard-dose cytarabine and daunorubicin as course two. Results are compared with forty-six patients achieving remission on the ALP2 study who received azacitidine and doxorubicin as consolidation course one and standard-dose cytarabine, daunorubicin, and thioguanine as course two. The ALP3 regimen resulted in a significantly improved 5-year disease-free survival of 32% +/- 19% versus 20% +/- 11% for the ALP2 study (P = .03). Survival from remission was also improved, 40% +/- 14% versus 24% +/- 12% (P less than .01). Favorable prognostic factors for disease-free survival included receiving the ALP3 treatment regimen, absence of a prior preleukemic syndrome, and female sex. These factors and younger patient age were significant for survival following first chemotherapy and survival after achieving remission. Six of 34 patients who relapsed after receiving the ALP3 regimen successfully achieved prolonged second remissions with high-dose cytarabine-based chemotherapy and/or allogeneic bone marrow transplantation (BMT). Overall survival for adults less than or equal to 45 years of age was 58% +/- 19% with the ALP3 postremission chemotherapy regimen, comparable to most studies of BMT for AML in first remission. Actuarial 5-year survival for ALP3 patients greater than 60 years of age was 18% +/- 20% with no improvement compared with ALP2.

Adult↗
PubMed1990

T-cell depletion to prevent graft-versus-host disease after bone marrow transplantation.

Graft-versus-host disease (GVHD) remains a major obstacle to successful bone marrow transplantation. Depletion of T lymphocytes from the donor marrow prior to transplantation substantially reduces the morbidity and mortality due to acute and chronic GVHD. Unfortunately, graft failure, usually due to rejection and leukemia relapse, are adversely affected by this approach. This article reviews current techniques for T-cell depletion and results of recent clinical trials directed to overcome major problem areas.

Bone Marrow Transplantation↗
PubMed1990

Bone marrow changes in patients with refractory aplastic anemia treated by recombinant GM-CSF.

The morphologic changes in the bone marrow of eight patients with refractory aplastic anemia who received 4 or more weeks of granulocyte macrophage-colony-stimulating factor (GM-CSF) are described. All eight patients demonstrated a continuous rise in the absolute number of neutrophils, eosinophils, and monocytes over the first four weeks of therapy. Bone marrow examination revealed a progressive increase in bone marrow cellularity in all patients except one. An increase in myeloid: erythroid ratio was seen with progressive maturation of granulocytic cells. Neutrophilic and eosinophilic myelocytes were the most prominent cells. The percentage of myeloblasts and promyelocytes did not increase significantly, and the proportions of postmitotic granulocytic cells did not change either. No significant morphologic changes were noted in the basophilic, erythroid, and megakaryocytic series. The most prominent topographic observation in the bone marrow during GM-CSF therapy was the frequent clustering of myeloid cells close to the bone trabeculae. The periosteal localization of myeloid precursors may reflect a higher concentration of stem cells and/or stromal cells in the bone marrow adjacent to the bone trabeculae or a higher concentration of growth factors. Careful morphologic examination of bone marrow in CSF clinical trials will provide useful information regarding the in vivo effects of these growth factors, and will aid in the development of a rational approach to combining them for therapy.

Anemia, Aplastic↗
PubMed1989

Immune thrombocytopenia in dogs after fetal liver hematopoietic cell transplantation.

Immune thrombocytopenia occurred in 6 of 33 engrafted dogs (18%) after fetal liver hematopoietic cell transplantation. Concurrent granulocytopenia occurred in three of six dogs and anemia in one. All dogs were receiving cyclosporin to prevent graft rejection and graft-versus-host disease (GVHD). None of the dogs had signs of GVHD. Bone marrow obtained at the time of platelet nadir was hypercellular with megakaryocyte hyperplasia. All dogs exhibited anti-megakaryocyte antibodies detected by direct immunofluorescence of bone marrow smears. Treatment with oral prednisolone resulted in normalization of platelet counts in five of six dogs and granulocyte and erythrocyte counts in dogs exhibiting concurrent leukopenia or anemia. Two long-term survivors (greater than 2.5 years) have not developed further hematologic abnormalities since initial diagnosis and treatment.

Animals↗
PubMed1988

Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro.

The Philadelphia chromosome is present in more than 95% of chronic myeloid leukemia patients and 13% of acute lymphocytic leukemia patients. The Philadelphia translocation, t(9;22), fuses the BCR and ABL genes resulting in the expression of leukemia-specific, chimeric BCR-ABL messenger RNAs. To facilitate diagnosis of these leukemias, we have developed a method of amplifying and detecting only the unique mRNA sequences, using an extension of the polymerase chain reaction technique. Diagnosis of chronic myeloid and acute lymphocytic leukemias by this procedure is rapid, much more sensitive than existing protocols, and independent of the presence or absence of an identifiable Philadelphia chromosome.

Cell Line↗
PubMed1987

Unique forms of the abl tyrosine kinase distinguish Ph1-positive CML from Ph1-positive ALL.

In the Philadelphia chromosome (Ph1) of chronic myelogenous leukemia (CML), the c-abl gene on chromosome 9 is translocated to bcr on chromosome 22. This results in the expression of a chimeric bcr-abl message that encodes the P210bcr-abl tyrosine kinase. The cells of 10% of acute lymphocytic leukemia patients (ALL) carry a cytogenetically similar Ph1 translocation. We report that Ph1-positive ALL cells express unique abl-derived tyrosine kinases of 185 and 180 kilodaltons that are distinct from the bcr-abl-derived P210 protein of CML. The appearance of the 185/180-kilodalton proteins correlates with the expression of a novel 6.5-kilobase messenger RNA. Thus, similar genetic translocations in two different leukemias result in the expression of distinct c-abl-derived products.

DNA, Neoplasm↗
PubMed1987

Transient response of pure red cell aplasia to anti-thymocyte globulin in a patient with T-cell chronic lymphocytic leukemia.

Pure red cell aplasia (PRCA) is an unusual complication of chronic lymphoproliferative disorders. A patient with T-cell chronic lymphocytic leukemia (T-CLL) had severe anemia and neutropenia. Initial in vitro studies demonstrated no evidence of T-cell suppression of erythropoiesis. Sequential bone marrow examinations demonstrated progressive red cell aplasia. In vitro studies showed that the T-cells from the patient suppressed allogeneic but not autologous BFU-E. Treatment with antithymocyte globulin (ATG) reduced circulating leukemic cells and produced a definite but transient improvement in erythropoiesis.

Adult↗
PubMed1987

Transplantation of DLA-compatible and incompatible fetal liver hematopoietic cells in dogs.

Requirements for sustained engraftment of fetal liver hematopoietic stem cells were evaluated in 45 dogs. Pretransplant preparative treatment with total-body irradiation, 14.7 Gy, permitted engraftment of DLA-compatible fetal liver cells. Radiation alone was inadequate in DLA-haploidentical or DLA-mismatched transplants; none of 5 dogs had engraftment. Addition of cyclosporine facilitated engraftment. The combination of 14.7 or 16.1 Gy total-body irradiation (TBI) and cyclosporine allowed engraftment in 15 of 19 (78%) dogs receiving DLA-histoincompatible grafts and 11 Gy TBI plus cyclosporine allowed engraftment in 4 of 10 dogs. Restoration of granulopoiesis and thrombopoiesis was rapid; recovery of lymphocytes was relatively delayed, especially in recipients of incompatible fetal liver cells. Cumulative one-year survival was decreased in recipients of incompatible grafts due to early posttransplant infections. These data suggest that fetal liver transplantation is a potential approach in patients who lack an HLA-identical donor for bone marrow transplantation.

Animals↗