Search PubMed⌕ Search

Biomedical subjects

J Sanders

Publications and source records attributed to J Sanders.

At least 163 records · Page 9Linked to original sources
PubMed1986

Decreased incidence of marrow graft rejection in patients with severe aplastic anemia: changing impact of risk factors.

Patients with severe aplastic anemia were conditioned with cyclophosphamide (200 mg/kg) and given marrow grafts from HLA-identical family members. Among 233 patients transplanted, 225 survived greater than or equal to 14 days and could be evaluated for engraftment. Forty-four of the 225 rejected their graft; 33 of these died and 11 survive. One hundred eighty-one patients had sustained engraftment; of these, 46 died and 135 survived. Binary logistic regression analyses revealed five risk factors for graft rejection: year of transplant, a large number of platelet transfusions, a positive relative response in mixed leukocyte culture, a low marrow cell dose, and omission of donor buffy coat cell infusion for transfused patients. These data show that patients transplanted recently had a lower likelihood of graft rejection than did patients transplanted in earlier years. Conceivably, this was related to changes in transfusion practices, but other factors as yet unidentified are likely to be involved. The data confirm that the largest possible number of marrow cells should be transplanted. Although the difference in the incidence of graft rejection between untransfused and transfused patients was not significant, it should be noted that transfused patients were given buffy coat cells. Because the addition of buffy coat cells results in a higher incidence of chronic graft-v-host disease (GVHD), it is still desirable to transplant patients with marrow alone early in their course before they have been transfused.

Anemia, Aplastic↗
PubMed1985

Treatment of acute graft-versus-host disease after allogeneic marrow transplantation. Randomized study comparing corticosteroids and cyclosporine.

Seventy-seven patients (age 12 to 46 years) who underwent allogeneic marrow transplantation for hematologic malignancy or aplastic anemia and who had grade II to IV acute graft-versus-host disease despite methotrexate prophylaxis were randomly assigned to receive methylprednisolone 2 mg/kg per day intravenously (n = 39) or cyclosporine (n = 38) either 12 to 15 mg/kg per day orally or 3 to 5 mg/kg per day intravenously. In both groups, clinical and histologic evidence of graft-versus-host disease was detected at medians of 16 and 25 days, respectively. Drugs were given for a minimum of 14 days unless significant deterioration occurred. If graft-versus-host disease did not improve with this therapy, treatment with a second agent was initiated. Treatment responses were scored after reviewing clinical and laboratory data collected before, during, and after the 14-day treatment period. Possible scores were as follows: -1, worse; 0, no change; + 1, improvement in one organ system (skin, liver, gut) with no deterioration in the other two; +2, complete resolution of all involved systems. The median response score among 39 methylprednisolone-treated patients was 0. Sixteen patients (41 percent) showed response to treatment, 11 with partial and five with complete response. The median response score among 38 cyclosporine-treated patients was +1. Twenty-three patients (61 percent) showed response to treatment, 15 with partial and eight with complete response (p = 0.039). Twenty patients receiving methylprednisolone and 18 receiving cyclosporine required additional therapy. The incidence of chronic graft-versus-host disease was similar in both groups. It developed in all nonresponding patients at risk who had received secondary therapy. Among responding patients (scores +1 or +2) who were not given additional treatment, chronic graft-versus-host disease developed in eight of 11 (72 percent) receiving methylprednisolone and five of ten (50 percent) receiving cyclosporine. Survival beyond 17 months was similar in the two groups (28 percent and 24 percent, respectively). These data suggest that cyclosporine is a useful agent for the treatment of acute graft-versus-host disease, comparable in its efficacy to methylprednisolone.

Acute Disease↗
PubMed1985

Autologous marrow transplantation in patients with acute nonlymphocytic leukemia in first remission.

Thirteen patients with acute nonlymphocytic leukemia underwent autologous bone marrow transplantation (ABMT) following high doses of cyclophosphamide and total body irradiation while in first complete remission. After marrow infusion four patients received human leukocyte interferon and nine received intravenous methotrexate. One patient died on day 16 of septicemia associated with severe gastrointestinal toxicity. In the remaining 12 patients the median day of achieving a circulating granulocyte level of 500/mm3 was 29 (range 15-94 days). Eight of 12 evaluable patients achieved a sustained platelet count of 20,000/mm3 or greater in a median of 44 days (range 12-116 days) and four patients did not achieve this level before death on days 116-396. One patient died on day 116 of interstitial pneumonitis secondary to cytomegalovirus. Eight patients relapsed 58-365 days after AMBT (median 335 days), and all have died. Three patients are alive and well without relapse 26-50 months after ABMT. This study demonstrated that poor engraftment was a frequent complication of ABMT when early posttransplant cytotoxic therapy was attempted. Relapse of leukemia and the number of long-term survivors in this small group of patients was not different from that expected following conventional therapy.

Acute Disease↗
PubMed1985

Marrow transplantation for treatment of pregnancy-associated aplastic anemia.

This report describes the results of marrow transplantation in four patients with aplastic anemia during the last trimester of their pregnancies. All patients were treated with supportive care until delivery. Because of persistent severe aplasia, marrow transplantation was then performed 1.6-11.0 months postpartum. Marrow donors were HLA-identical siblings. Although all were at increased risk for graft rejection because of their pregnancies as well as their long transfusion histories, two patients were successfully engrafted and now survive 12 and 95 months after transplant. The other two patients rejected their grafts despite attempts at second or third marrow infusions. Both died of infectious complications, 42 and 111 days after transplant.

Adult↗
PubMed1984

Evidence for a stem cell common to hematopoiesis and its in vitro microenvironment: studies of patients with clonal hematopoietic neoplasia.

The origin and nature of cells forming the in vitro microenvironment in long-term cultures of human marrow were studied in five patients with clonal myeloproliferative disorders who were heterozygous for glucose-6-phosphatase dehydrogenase (G6PD). The results showed that cells in the adherent stromal layer forming the in vitro microenvironment were derived from the same clonal progenitors involved by the neoplasm in the four patients whose diseases originated in multipotent stem cells. In contrast, stromal cells were derived from normal progenitors in a patient with acute non-lymphocytic leukemia whose clone showed differentiative expression confined to cells in the granulocytic lineage. Mixing experiments demonstrated that the G6PD type displayed by the adherent marrow stromal cells was not obscured by contaminating non-adherent hematopoietic cells or marrow fibroblasts. The data suggest the existence of a pluripotent cell in normal hematopoiesis that gives rise to hematopoietic cells and to their micro-environment.

Adult↗
PubMed1984

Allogeneic marrow transplantation in the treatment of preleukemia.

Ten patients with preleukemia and life-threatening pancytopenia were treated with marrow transplantation. In all ten cases allogeneic marrow was successfully engrafted. In three patients prepared for transplantation with cyclophosphamide alone, the abnormal cell clone either persisted or reemerged within 6 months of transplantation. The other seven patients were treated with cyclophosphamide plus total body irradiation before transplantation and six of the seven are alive and well without evidence of disease from 7 to 25 months after transplantation. These results suggest that cyclophosphamide alone before marrow transplantation is incapable of eradicating the abnormal clone. Cyclophosphamide combined with total body irradiation appears more effective, although more time is needed for full evaluation of results. This experience also emphasizes the importance of performing chromosome studies before transplantation for pancytopenic states in order to identify cases of preleukemia.

Adolescent↗
PubMed1984

Secondary malignancies after marrow transplantation.

Secondary malignancies after marrow transplantation have been observed in 20 patients: 19 patients underwent marrow transplantation for the treatment of a hemopoietic malignancy and one for aplastic anemia. All but three were given total body irradiation at doses of 8.0-15.75 Gy as part of the conditioning regimen. Secondary malignancies were composed of three groups: (a) Six patients had recurrence of leukemia (three acute lymphoblastic, two acute myeloblastic, and one chronic myelocytic) in cells of donor origin 62-1074 days after grafting. (b) Eight patients developed lymphoproliferative disorders (four of immunoblastic sarcoma type, one lymphoblastic, one follicular center cell, and one Hodgkin's lymphoma and one acute lymphoblastic leukemia) 54-730 days after grafting. In four of seven patients with appropriate studies these tumors were of donor-cell origin and in three of four tested the cells contained Epstein-Barr virus genome or expressed viral antigens. (c) Six patients developed solid tumors (two glioblastoma multiforme, two adenocarcinomas, one squamous cell carcinoma, and one sarcoma) 347-1875 days after grafting. All but two patients (one with glioblastoma and one with squamous cell carcinoma) have died. These data suggest that patients undergoing marrow transplantation for a hemopoietic malignancy may be at risk of developing secondary malignancies. The etiology appears to be multifactorial, including irradiation, immunosuppression, Epstein-Barr virus infections, and other factors.

Adolescent↗
PubMed1983

Transfusion requirements after HLA-identical marrow transplantation in 82 patients with aplastic anemia.

Red blood cell (RBC) and platelet (PLT) transfusion requirements during the first 13 weeks after HLA-identical marrow transplantation were studied in 82 patients with aplastic anemia. On the average, patients were given 9 units of RBCs (1-82) and 44 units of PLTS (6-468). The greatest need for support was during the first 4 weeks postgrafting. A multivariate statistical analysis of 22 variables showed that RBC and PLT requirements increased with age. In addition, RBC requirements increased if the patient had isohemagglutinins against the marrow donor's RBC, i.e., if the marrow transplant was across a major ABO barrier.

ABO Blood-Group System↗
PubMed1983

Intensive chemoradiotherapy with autologous marrow transplantation for small cell carcinoma of the lung.

Ten patients with small cell carcinoma of the lung (seven with extensive and three with limited disease) underwent several courses of conventional therapy. The patients were then referred for autologous marrow transplantation, three during a complete response, six during a partial response, and one following no response. The pretransplantation regimen consisted of 120 mg/kg of cyclophosphamide followed by 800-1000 rad of total-body irradiation. In addition, six of the seven patients with extensive disease received high-dose nitrosourea. Following the infusion of cryopreserved autologous marrow, all patients achieved engraftment. Of the three patients without detectable tumor at the time of transplant, two died with tumor present and one survives without recurrence 27 months after transplantation. Of the other seven patients, two had a complete tumor response; both died of interstitial pneumonitis, one without detectable tumor and one with microscopic tumor at autopsy. One of the other five patients had a partial response, but all died of tumor progression. The median survival from initial therapy in patients with extensive disease was 9 months and with limited disease was 18.5 months.

Autopsy↗
PubMed1982

Treatment of chronic granulocytic leukaemia in chronic phase by allogeneic marrow transplantation.

Ten patients with chronic granulocytic leukaemia in the chronic phase have been treated with chemoradiotherapy followed by transplantation of bone marrow from HLA-identical siblings. Engraftment was achieved in all patients, and Philadelphia chromosome disappeared from the nine patients who had it before transplantation. Four patients have died, three with interstitial pneumonitis and one with severe graft-versus-host disease (GvHD). Six patients are alive and well in complete clinical, cytogenetic, and haematological remission, 1-3 years after transplantation, despite complications in three patients (one had interstitial pneumonitis, one had mild veno-occlusive disease of the liver, and one had severe GvHD).

Adult↗
PubMed1982

Donor origin of the in vitro haematopoietic microenvironment after marrow transplantation in man.

The method for long-term culture of marrow cells in vitro as described by Dexter has recently been successfully applied to human marrow and is dependent on the development of an adherent stromal cell layer consisting of cells described as "endothelial-like cells, fat cells, and macrophages". The present study was designed to determine the origin and composition of the stromal cells forming the in vitro 'microenvironment' and maintaining haematopoiesis in long-term cultures grown from marrows of 14 patients who received marrow transplants from HLA identical siblings of the opposite sex. The presence of a Y chromosome was used as a marker to establish the donor or recipient origin of the cells. We found that the stromal cells became progressively donor in origin with time after transplantation and some reacted with antibody directed against factor VIII-associated antigen. In addition, donor-derived in vitro stromal cells synthesized both interstitial and basal lamina collagen types, indicating that the in vitro microenvironment is transplantable and composed in part of endothelial-like cells.

Adipose Tissue↗
PubMed1982

An assessment of the fibrinolytic system in hemophilia A.

The fibrinolytic system was assessed in 28 hemophiliacs using the chromogenic substrate H-D-Val-Leu-Lys-pNA. To determine whether a state of hyperfibrinolysis might be associated with Factor VIII replacement therapy, 14 patients with severe disease who were intensively treated with Factor VIII concentrates were compared with 14 patients with mild disease who were receiving infrequent transfusions with cryoprecipitate or fresh frozen plasma. Seventeen normal males served as controls. With the exception of an elevated level of plasminogen activator and a decreased level of immediate antiplasmin in the mild group only, no evidence of enhanced fibrinolysis was found. Other components of the fibrinolytic system were either normal (plasmin) or increased (progressive antiplasmin containing both alpha 2PI and alpha 2M, and plasminogen). The elevated plasminogen levels were found only in the severe intensively transfused group. The elevated progressive antiplasmin levels were found in both groups of patients and did not appear to be related to transfusions. These findings do not support the concept of enhanced fibrinolysis associated with intensive Factor VIII replacement therapy.

Adolescent↗