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Biomedical subjects

R Storb

Publications and source records attributed to R Storb.

At least 703 records · Page 39Linked to original sources
PubMed1980

Analysis of cytotoxic effector cell function in patients with leukemia or aplastic anemia before and after marrow transplantation.

Cytotoxic effector cells mediating natural killing (NK), antibody-dependent cellular cytotoxicity (ADCC), and lectin-dependent cellular cytotoxicity (LDCC) were studied in patients with leukemia or aplastic anemia before and/or after marrow transplantation. Before transplantation, about one-third to one-half of the patients were deficient in cytotoxic activity. In patients with leukemia, this was most likely due to large numbers of circulating blast cells diluting or replacing the effector cells. In patients with aplastic anemia there was an apparent absence of the effector cells in a proportion of the patients. After marrow transplantation, cytotoxic activity in all three systems returned to normal rapidly, by 30 days, and remained so through 100 days. However, about 20% of patients studied beyond 1 year were deficient in these functions. There were no significant associations between cytotoxic activity and important clinical parameters including infections, graft-vs-host disease, and recurrence of leukemia. Our findings do not support an immunosurveillance role for NK against leukemia after marrow transplantation. Furthermore, they point out the need for new in vitro approaches for meaningful monitoring of marrow transplant patients. Finally, our results showed a significant discordance between NK, ADCC, and LDCC activities in these immunologically perturbed individuals, indicating that either different cell populations or different cellular mechanisms are involved in these cytotoxic functions.

Anemia, Aplastic↗
PubMed1980

Increased in vitro B-cell IgG secretion during acute graft-versus-host disease and infection. Observations in 50 human marrow transplant recipients.

B-cell antibody secretion by lymphocytes from 50 bone marrow transplant recipients and 42 healthy controls was studied in vitro using an indirect hemolysis-in-gel assay to determine Ig-class-specific plaque-forming cells (PFC). The numbers of PFC were determined in medium alone and after stimulation of lymphocytes with killed Staphylococcus aureus bacteria. The PFC responses for IgG, IgA, and IgM after stimulation with S. aureus were significantly lower in patients studied during the first 101 days after grafting compared to normals. Statistically significant increased IgG-PFC were found in patients who had acute graft-vesus-host disease (GVHD), grafts from HLA-nonidentical donors, or infections. Healthy patients studied more than 1 yr following transplantation had normal B-cell responses, but patients with chronic GVHD had deficient IgM production. The data suggest that antibody secretion by B cells varies in different marrow transplant patient subgroups and present a basis for further investigation of the interaction between lymphocyte subpopulations leading to antibody production.

Acute Disease↗
PubMed1980

Successful pregnancy after high dose chemotherapy and marrow transplantation for treatment of aplastic anemia.

A 29-year-old woman with severe idiopathic aplastic anemia was given immunosuppressive therapy with procarbazine, 37.5 mg/kg, antithymocyte globulin, 36 mg IgG/kg, and cyclophosphamide, 200 mg/kg. This was followed by a marrow transplant from her HLA identical sister, immunosuppressive therapy with intermittent methotrexate for 3 months postgrafting and ultimate restoration of hematopoiesis. Two years after transplantation the patient delivered a healthy male infant. This is the first successful pregnancy after a high dose chemotherapy and marrow transplantation for treatment of aplastic anemia.

Adult↗
PubMed1980

Granulocyte function in human allogenic marrow graft recipients.

Granulocyte chemotaxis and iodination were studied in 87 allogeneic marrow transplant recipients and in 25 normal individuals. Chemotactic responses of marrow transplant recipients as a group were depressed during the first 4 months after transplantation and normal in patients studied as long-term survivors (days 175--2202 post-transplantation). Patients with moderate to severe acute or chronic graft-versus-host disease (GVHD) or infections had lower chemotactic responses than those without. Granulocyte iodination and the ability of patient serum to support iodination were normal. Thus, depressed granulocyte chemotaxis recovered slowly with time following allogeneic marrow transplantation. Both acute and chronic GVHD, however, were associated with impairment of granulocyte chemotaxis, a defect which may contribute to the high risk of infection among allogeneic marrow graft recipients with GVHD.

Adolescent↗
PubMed1980

In vitro tests for distinguishing possible immune-mediated aplastic anemia from transfusion-induced sensitization.

Forty-two patients with aplastic anemia (AA) were studied to determine whether or not transfusion-induced sensitization is responsible for the in vitro inhibition by patient lymphocytes of HLA-identical erythroid burst-forming units (BFU-E). The results indicate that lymphocytes from 12 of 34 transfused patients inhibited normal colony growth. In contrast, lymphocytes from none of the 8 untransfused patients demonstrated inhibition. These data were interpreted to mean that coculture studies would not be useful for identifying immune-mediated AA in transfused patients. Therefore, in order to identify possible immune-related AA, we assayed BFU-E from patient blood before and after T-cell depletion. In all 32 patients studied, BFU-E failed to grow from peripheral blood cells before T-cell depletion, but in 8 cases, normal-appearing BFU-E grew after T cells had been removed. Growth of patient BFU-E colonies was inhibited in 6 cases when patient T cells were added back to the culture, indicating that in these 6 patients, an "autoimmune" mechanism may have been present.

Anemia, Aplastic↗
PubMed1979

Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts.

To determine whether allogeneic bone-marrow transplantation is associated with a graft-versus-leukemia effect, we examined the relation between relapse of leukemia and graft-versus-host disease in 46 recipients of identical-twin (syngeneic) marrow, 117 recipients of HLA-identical-sibling (allogeneic) marrow with no or minimal graft-versus-host disease, and 79 recipients of allogeneic marrow with moderate to severe or chronic disease. The relative relapse rate was 2.5 times less in allogeneic-marrow recipients with graft-versus-host disease than in recipients without it (P less than 0.01). This apparent antileukemic effect was more marked in patients with lymphoblastic than nonlymphoblastic leukemia, and in those who received transplants during relapse rather than during remission, and was most evident during the first 130 days after transplantation. Survival of all patients was comparable since the lesser probability of recurrent leukemia in patients with graft-versus-host disease was offset by a greater probability of other causes of death.

Acute Disease↗
PubMed1979

Disappearance of Ph1-positive cells in four patients with chronic granulocytic leukemia after chemotherapy, irradiation and marrow transplantation from an identical twin.

Four patients (21, 41, 13 and 38 years of age) with a history of chronic granulocytic leukemia for 12, 10, 11, and 106 months, respectively, were treated with dimethyl busulfan, cyclophosphamide, 920 rads of total-body irradiation and intravenous marrow infusion from normal, genetically identical twins. Serial chromosome analyses were performed on marrow aspirates cultured without mitotic stimulants. No Ph1-positive cells were detected in the marrows from the normal twins, whereas just before therapy, all 100 metaphases examined from each patient were Ph1-positive. Chromosome analyses were performed three to five times per patient after transplantation, and not a single Ph1-positive cell was detected. The patients remain hematologically normal 22, 23, 26 and 31 months after transplantation. The results show that the Ph1-positive clone can be eradicated by vigorous therapy and that the marrow in chronic granulocytic leukemia can be repopulated by stem cells from normal twins.

Adult↗
PubMed1979

Effect of trimethoprim-sulfamethoxazole on hematological recovery after total body irradiation and autologous marrow infusion in dogs.

To test the effect of the combination of trimethoprim-sulfamethoxazole (TMP-SMX) on hematological recovery after bone marrow transplantation, dogs were conditioned with 1,200 R total body irradiation and then infused with autologous marrow. Twenty dogs were given TMP-SMX at doses equivalent to 10, 20, or 40 mg TMP/kg/day beginning on the day of marrow infusion and continued until the granulocyte count reached 10(3)/mul; in addition, one-half of the dogs received methotrexate, 0.4 mg/kg on days 1, 3, 6, and 11 and then weekly until termination of the study. Granulocyte and platelet changes were compared to those of dogs given 1,200 R, autologous marrow infusion, and no TMP-SMX. Dogs given 10 and 20 mg TMP/kg/day had normal granulocyte and platelet recovery after irradiation. Dogs given 40 mg TMP/kg/day showed a significant delay in granulocyte recovery and mildly delayed platelet recovery. This suggests that TMP-SMX in prophylactic doses (5 mg TMP/kg/day) can be given safely to human patients immediately after allogeneic marrow transplantation and thus probably prevent even very early cases of Pneumocystis carinii pneumonia, and possibly bacterial infections as well.

Animals↗
PubMed1979

Association of interstitial pneumonia and diminished in vitro lymphocyte blastogenesis in human marrow graft recipients.

The lymphocyte responses of 51 human marrow graft recipients were tested in vitro 18 to 45 days after marrow grafting by stimulation with lymphocytes from unrelated individuals or phytohemagglutinin (PHA). Fourteen of the 51 patients subsequently developed interstitial pneumonia (IP). The relative responses of the lymphocytes of patients who developed IP were significantly lower than those of individuals not developing IP (P less than 0.01 for allogeneic cells, P = 0.02 for PHA). These nonspecific in vitro tests of cell-mediated immunity are of value in identifying patients at risk of developing IP.

Anemia, Aplastic↗