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Biomedical subjects

R Storb

Publications and source records attributed to R Storb.

At least 667 records · Page 37Linked to original sources
PubMed1981

Studies of the response in mixed leukocyte culture of cells from patients with aplastic anemia to cells from HLA-identical siblings.

We have studied the mixed leukocyte culture (MLC) reactions of 64 patients with severe aplastic anemia. Their peripheral blood mononuclear cells showed an increased relative response (RR) to cells from HLA-identical siblings as compared to cells from normal HLA-identical siblings, confirming the results reported in an earlier series of 34 patients. Elevated RRs were associated with patient antidonor lymphocyte antibodies as detected by the antibody-dependent cell-mediated cytotoxicity assay, but were not associated with antidonor complement-dependent cytotoxic antibodies or with antidonor cytotoxic T lymphocytes. Among 98 patients receiving marrow grafts from HLA-identical sibling donors, those with elevated RRs before transplantation were more apt to reject the transplant than those without (P less than 0.0001). There was no elevation of the RR in 10 untransfused patients, although positive RRs were noted in 2 patients within 12 to 24 hr of their first transfusions. Five patients with identical twins were also tested, and elevated RRs were noted in three. Although blood transfusion appears to be responsible for the increased RRs observed in some aplastic patients, genetic differences between donor and recipient were not always necessary for eliciting an increased MLC response, suggesting that mechanisms other than alloimmunization are involved.

Adolescent↗
PubMed1981

Detection of the leukocyte group-5 antigens on normal and leukemic lymphocytes with the antibody-dependent cell-mediated cytotoxicity assay.

We have found that the antibody-dependent call-mediated cytotoxicity (ADCC) assay is capable of detecting the alleles of the group-5 antigenic system on peripheral blood lymphocytes. This finding should facilitate additional study of this system, as illustrated by the detection of group-5 antigens on leukemic cells, indicating that they are not lost from the cell surface upon malignant transformation.

Agglutination Tests↗
PubMed1981

Increased frequency of the group 5a antigen in patients with hematologic malignancies.

We have confirmed our previously described finding that the group-5a antigen is associated with acute lymphoblastic leukemia. In addition we have found that the 5a antigen has an increased frequency in patients with chronic lymphocytic lymphoma but not in patients with acute myelogenous leukemia, acute myelomonocytic leukemia. Hodgkin's disease or histiocytic lymphoma.

Adult↗
PubMed1981

Recovery of antibody production in human allogeneic marrow graft recipients: influence of time posttransplantation, the presence or absence of chronic graft-versus-host disease, and antithymocyte globulin treatment.

One-hundred fifty-three recipients of HLA-identical sibling marrow transplants for aplastic anemia or hematologic malignancy were injected with bacteriophage phi X174 (phage), pneumococcal polysaccharide antigen (PPA), or keyhole limpet hemocyanin (KLH). Antibody levels were determined several times in the 6 wk after injection. Multiple regression techniques were used to determine what factors played significant roles in the antibody response. The most significant factors were the time elapsed from transplantation, chronic graft-versus-host disease (GVHD), and antithymocyte globulin (ATG) treatment. All patients had low antibody responses to all antigens in the first 180 days from transplant. Beyond 180 days patients without chronic GVHD showed antibody responses indistinguishable from those of normal donors. However, patients with chronic GVHD had the following impairments: (1) primary response to phage, (2) conversion from IgM to IgG in secondary response to phage, (3) secondary response to KLH, and (4) response to PPA. ATG treatment given to patients either prophylactically or therapeutically for acute GVHD was followed by lower primary responses to phage in the first 180 days and poor ability to switch from IgM to IgG antibody in the secondary response beyond 180 days postgrafting. Other factors did not yield additional significant information about ability to predict antibody responses including diagnosis, conditioning regimen, treatment in or out of laminar air flow rooms, transplantation, pretransplant refractoriness of the recipient to platelet transfusions from random donors, donor age or donor sex, and steroid administration for treatment for prevention of GVHD. The data indicate that, given enough time after transplantation, the ability to produce normal antibody function recovers except in those patients experiencing chronic GVHD.

Antibodies↗
PubMed1981

Specific suppressor cells and immune response to host antigens in long-term human allogeneic marrow recipients: implications for the mechanisms of graft-host tolerance and chronic graft-versus-host disease.

After marrow grafting from HLA-identical siblings, anti-host immune reactivity and suppressor activity were examined in long-term patients with and without C-GVHD. Lymphocytes (of donor origin) from 17 of 32 patients with C-GVHD showed MLR to non-HLA antigens of stored host lymphocytes, and lymphocytes from 8 of 21 patients with C-GVHD exhibited cytotoxicity to host skin fibroblasts. Lymphocytes from only 2 of 15 patients without C-GVHD, however, showed significant MLR to host lymphocytes and none of 16 had cytotoxicity to host fibroblasts. Suppressor activities differed in the two patient groups. Patients without C-GVHD had circulating suppressor cells that specifically inhibited donor MLR to TNP-host lymphocytes but not to TNP-donor, TNP-unrelated and unmodified unrelated lymphocytes. On the other hand, patients with C-GVHD had predominantly suppressor cells that inhibited donor MLR to TNP-unrelated and unmodified unrelated lymphocytes. These findings indicate that anti-host immune reactivity in the absence of specific suppressor cells plays a role in C-GVHD, and that graft-host tolerance in the stable chimeras may be maintained by specific suppressor cells.

Acute Disease↗
PubMed1981

Long-term survival and reversal of iron overload after marrow transplantation in dogs with congenital hemolytic anemia.

Severe hemolytic in Basenji dogs secondary to pyruvate kinase deficiency was corrected by marrow transplantation from hematologically normal littermates. These dogs have now been followed for more than 5.5 yr. Essentially normal hematopoiesis has persisted, and the dogs remain in good health without cirrhosis or osteosclerosis. Furthermore, hepatic iron overload present before transplantation has gradually decreased. These results in dogs suggest that marrow transplantation could prevent the morbidity and mortality of severe hemolytic anemia and associated iron overload in man.

Anemia, Hemolytic, Congenital↗
PubMed1981

Nonspecific acid esterase activity as a marker for canine T lymphocytes.

Canine T lymphocytes are as yet poorly defined. Since focal paranuclear positivity for nonspecific esterase (alpha-naphthyl acetate esterase--ANAE) has been shown to be a reliable marker for T cells in humans and mice, canine lymphoid tissue sections, and cell suspensions were stained for this enzyme. Sections of five lymph nodes and 11 puppy thymuses displayed the same distribution patterns of focally ANAE-positive cells as were found in humans and mice in both organs: in thymuses only the medulla contained positive cells, and in lymph nodes only the thymus-dependent, paracortical zones, but not central areas of germinal centers, displayed focal ANAE reactivity. Furthermore, 56-78% of peripheral blood mononuclear cells, 60-71% of thoracic duct lymphocytes, and 10-15% of suspended thymus cells were positive for ANAE. It is concluded that focal ANAE reactivity is a marker for a canine T cell subpopulation.

Animals↗
PubMed1981

Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression.

Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases. Thirteen patients with extensive disease (group I) were not treated and only 2 survive with Karnofsky scores >- 70%. Mortality resulted from infections and morbidity from sica syndrome, pulmonary and hepatic insufficiency, scleroderma-like skin disease, and contractures. Another 13 (group II) received a median of 8 mo prednisone and/or a brief course of antithymocyte globulin, and 3 survive without disability. The other 21 (group III) were treated with a combination of prednisone (1.0 mg/kg/q.o.d.) and either cyclophosphamide, procarbazine, or azathioprine (all 1.5 mg/kg/day) for a median of 13 mo. Combination therapy was well tolerated with only modest myelotoxicity. Fifteen in group III had a good and 4 a fair response to treatment while 2 with no response died. Azathioprine and prednisone was the most effective regimen. All therapy has been discontinued in 12 group III patients: GVHD returned in 5 (including 2 who died in spite of retreatment) while 7 remain free of GVHD for a median of 11 (range 6-30) mo observation. Only I group III survivor is disabled and 16 of the original 21 are alive 2-4 yr after transplant with Karnofsky scores of 70%-100%. Thus, combination immmunosuppression appears to favorably affect and, in some cases, premanently arrest the adverse natural course of extensive chronic GVHD.

Antilymphocyte Serum↗
PubMed1981

Bone marrow transplantation for refractory acute leukemia in 34 patients with identical twins.

Thirty-four patients aged 4-67 yr (median 17) with acute lymphocytic leukemia (ALL) (18 patients) or acute nonlymphocytic leukemia (ANL) (16 patients) who failed to enter complete remission (CR) or relapsed on conventional chemotherapy were treated with cyclophosphamide (CY), 60 mg/kg/day for 2 days, 1000 rad total body irradiation, and a marrow transplant from a genotypically identical normal twin. Sixteen of the patients received additional chemotherapy within the week before CY. After the transplant, 23 patients received immunotherapy consisting of killed autologous leukemic cells and/or normal twin peripheral blood lymphocytes, 16 as part of a prospectively randomized study. One moribund patient died before engraftment. Nine patients (6 ALL, 3 ANL) continued to have detectable leukemic cells. Twenty-four patients (70%) achieved CR. One of them died of viral hepatitis at 1 mo and another of viral interstitial pneumonitis at 4 mo in CR. Fourteen patients (7 ALL, 7 ANL) relapsed 2-16 mo (median 4) after transplantation. However, 8 patients (24%) (3 ALL, 5 ANL) remain in CR without any maintenance chemotherapy at 29-103 mo (median 80) after the transplant. The end results were not signficantly influenced by the type of leukemia, the immediated pre-CY chemotherapy, or the immunotherapy. The results show that this approach, even when applied to endstage patients with acute leukemia in relapse, causes tolerable morbidity, rare nonleukemic deaths, and frequent remissions, some of which represent cures.

Acute Disease↗
PubMed1981

Transfusion problems associated with transplantation.

We have reviewed the role of blood transfusions in renal and marrow graft recipients. Striking contrasts are evident: while transfusions may promote successful kidney grafting, any transfusions before initiation of the transplant conditioning regimen may jeopardize the treatment of severe aplastic anemia by marrow transplantation. We have suggested guidelines for the transfusion support of transplant candidates before transplantation and for marrow graft recipients after transplantation. It is important to recognize that after conditioning for marrow transplantation, all patients will be profoundly pancytopenic for a limited period of time, and intensive transfusion support is vital to patient survival.

Acute Disease↗
PubMed1981

Treatment of non-Hodgkin's lymphoma with marrow transplantation in identical twins.

Eight patients with disseminated non-Hodgkin's lymphoma who failed conventional combination chemotherapy were treated with high-dose chemotherapy, a supralethal dose of total-body irradiation, and a bone marrow transplant from a normal identical twin. Seven patients experienced complete remission. Four of the seven patients (two with diffuse poorly differentiated lymphocytic lymphoma, one with composite lymphoma, and one with diffuse moderately well differentiated lymphocytic lymphoma) remain in complete unmaintained remission 12-126 mo from transplantation. One patient relapsed after 10 mo but was retreated and is alive in unmaintained complete remission 73 mo from transplantation. One patient died of Pseudomonas pneumonia while in complete remission and one patient relapsed and died of progressive lymphoma. These results demonstrate that intensive chemoradiotherapy and twin marrow transplantation can induce frequent and enduring remissions in patients with disseminated non-Hodgkin's lymphoma who have failed conventional therapy.

Adolescent↗