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Biomedical subjects

F R Appelbaum

Publications and source records attributed to F R Appelbaum.

At least 397 records · Page 22Linked to original sources
PubMed1987

Allogeneic and syngeneic marrow transplantation following high dose dimethylbusulfan, cyclophosphamide and total body irradiation.

Fifty-eight patients received an allogeneic or syngeneic marrow transplant following conditioning with high doses of dimethylbusulfan (DMB), cyclophosphamide (CY) and total body irradiation (TBI). Thirty-two patients had either chronic myeloid leukemia (CML) in accelerated phase or blast transformation, or acute leukemia after first relapse. The actuarial survival of these 32 patients at 3 years was 12% compared with 25% for a group of 206 patients with similar diagnoses prepared for transplantation with CY and TBI alone. This reduced survival was associated with a greater incidence of early non-leukemic deaths, in particular as a result of severe hepatic veno-occlusive disease. The incidence of leukemic relapse was not different in the two groups. Of 13 patients with CML in chronic phase who received syngeneic transplants following DMB, CY and TBI, nine are alive in hematologic and cytogenetic remission from 3.9 to 9.4 (median 6.2) years post-transplant.

Adolescent↗
PubMed1987

Marrow transplantation for malignant lymphoma.

With a large number of patients treated, some more than a decade ago, it is now clear that the use of high-dose therapy combined with marrow transplantation can cure some patients of malignant lymphoma who are otherwise incurable. Two major questions which are considered in this review are: (1) how can currently available transplant techniques be best applied, and (2) how do we go about developing more effective transplant regimens?

Bone Marrow Transplantation↗
PubMed1987

The treatment of acute non-lymphoblastic leukemia by allogeneic marrow transplantation.

The results are presented of allogeneic transplantation for 363 patients with acute non-lymphoblastic leukemia treated in Seattle from May 1973 through December 1985. The probabilities of surviving disease-free for 5 years for patients transplanted in first remission, in second remission, in untreated first relapse or in chemotherapy-resistant first relapse were 46%, 28%, 30%, and 21%, respectively. The corresponding probabilities of relapse within 5 years were 25%, 37%, 36% and 56%, respectively. Prognostic factors predictive of survival after marrow transplantation for patients transplanted in first remission included age, donor sex and the number of circulating blasts at the time of diagnosis. Acute graft-versus-host disease (GVHD) had a major adverse effect on survival, but chronic GVHD decreased the risk of relapse for patients transplanted in first remission.

Bone Marrow Transplantation↗
PubMed1987

Marrow transplantation for patients with acute lymphoblastic leukemia in first marrow remission.

Forty-six patients with acute lymphoblastic leukemia (ALL) in first marrow remission underwent allogeneic marrow transplantation between August 1976 and June 1985. Thirty-four patients had no extramedullary disease after remission induction and 12 had extramedullary relapses prior to or at the time of marrow grafting. The conditioning regimen included cyclophosphamide followed by total body irradiation, 9.2-15.75 Gy, administered as a single dose or in six or seven daily fractions. Marrow donors were genotypically HLA-identical siblings. Methotrexate was given as prophylaxis for graft-versus-host disease (GVHD). Forty-four patients had marrow engraftment. The incidence of grades II-IV acute GVHD was 52%. Clinical chronic GVHD occurred in 21 patients. Eighteen patients are alive 1-9 years (median = 4.2 years) after marrow grafting, 15 of whom are in continuous complete remission. The estimated probability of relapse within 2 years (+/- standard error) is 41 +/- 9% and the probability of relapse-free survival at 5 years is 28 +/- 7%. Major causes of death were recurrent leukemia, acute GVHD and interstitial pneumonia. Actuarial probabilities of survival, relapse and disease-free survival were not significantly different between those patients who did and those who did not have extramedullary disease after attaining first marrow remission.

Bone Marrow Transplantation↗
PubMed1987

Treatment of aplastic anemia with antithymocyte globulin, high-dose corticosteroids, and androgens.

A total of 46 patients with aplastic anemia (34 severe; 12 moderate) were treated with antihuman thymocyte globulin (ATG), high-dose methylprednisolone, and oxymetholone. Early symptoms of ATG toxicity included fever, rash, and bronchospasm. Signs of serum sickness also developed in 23 patients. Complications associated with high doses of steroids were hyperglycemia, hypertension, fluid retention, gastrointestinal hemorrhage, and aseptic necrosis of the hip. Other morbidity possible associated with steroid administration included seizures, arrhythmias, and headache with papilledema. Studies of elevated liver function necessitated discontinuation of androgen therapy in eight patients. A complete or partial hematological response was noted in 19 patients (41%). Of these, three have had recurrent cytopenias, of whom one has developed a myelodysplastic syndrome. There are currently 34 patients surviving, and 12 who have died. Actuarial survival at three years is 65%. These response and survival data are comparable to those of previous trials using ATG and androgens without high-dose steroids. A prospective, randomized trial is needed to determine whether the addition of high-dose corticosteroids to ATG does significantly increase the rate and frequency of response in order to justify the toxicity of this additional immunosuppressive therapy in the treatment of aplastic anemia.

Adult↗
PubMed1987

Treatment of preleukemic syndromes with marrow transplantation.

Thirty patients with advanced preleukemic syndromes were treated with marrow transplantation. Most cases were diagnosed by the presence of peripheral pancytopenia and a diagnostic marrow examination but in 6 of the 30 patients pretransplant chromosome studies were instrumental in establishing the diagnosis. Three patients prepared for transplantation with cyclophosphamide alone recurred with their disease within 6 months of transplantation. The other 27 patients were treated with cyclophosphamide and total body irradiation. Twenty of these 27 patients had preleukemia not associated with prior therapy or severe marrow fibrosis. Thirteen of these 20 are alive and well 9 to 56 months from transplant and 7 died, 4 of interstitial pneumonia, 2 of candida septicemia, and 1 of disseminated zoster. There have been no disease recurrences in this group. The remaining preleukemic patients, which include 3 patients transplanted for preleukemia secondary to prior therapy and 4 patients transplanted for preleukemia associated with severe marrow fibrosis, have all died. Major problems in these patients included disease recurrence (2 cases) and, in those with severe marrow fibrosis, graft failure (2 cases). These results suggest that for patients with life-threatening pancytopenia due to spontaneous preleukemia without severe marrow fibrosis, marrow transplantation can prolong disease-free survival and may result in cure of the disease.

Bone Marrow Transplantation↗
PubMed1987

Use of iodine-131-labeled anti-immune response-associated monoclonal antibody as preparative regimen prior to bone marrow transplantation: initial dosimetry.

Despite the use of near maximal doses of external beam total-body irradiation, many patients who received transplants for relapsed hematologic cancers will fail because of tumor recurrence following therapy. With the use of radioisotope-labeled monoclonal antibodies, a more directed delivery of systemic radiotherapy may be achieved; tumor cell kill is increased without increased toxicity. On the basis of this hypothesis, we have begun dosimetry studies in normal dogs using an anti-immune response-associated antibody (7.2) labeled with 131I. Compared with an irrelevant isotype-matched antibody, the blood concentration of 131I-labeled 7.2 fell rapidly over the first 3 hours and then cleared more slowly. During this time, there was specific localization of 131I-7.2 in lymph nodes, spleen, and marrow. On the basis of the concentration curves generated over 48 hours, administration of enough 131I-7.2 to deliver 10 Grays to the blood would result in radiation doses of 9.8, 16.3, and 32.3 Grays to liver, marrow, and spleen, respectively. The liver uptake of labeled 7.2 appeared to be the result of its direct antigen-specific binding to hepatic Kupffer cells rather than to the clearance by the liver of either antigen-antibody complexes or antibody-coated cells. Gastric or intestinal radiation toxicity may be a problem due to gastric excretion of free I following binding of 131I-7.2 and subsequent deiodination.

Animals↗
PubMed1986

Cyclic neutropenia as a premalignant manifestation of acute lymphoblastic leukemia.

A 20-year-old female from the Philippines developed anemia and granulocytopenia. With androgen therapy, her anemia improved but she continued to show a pattern of fluctuating neutropenia consistent with human cyclic neutropenia: Blood neutrophil oscillation was regular with a periodicity of 21 days. She developed recurrent pharyngitis and apthous stomatitis but there was no cycling of other blood elements. Bone marrow aspiration and biopsy showed normal developing myeloid cells, a clonal chromosomal abnormality, and myelofibrosis. During the fourth documented cycle, blasts appeared and complete lymphoblastic transformation ensued. Blast cells were CALLA positive, Ia positive, and contained intranuclear TdT; they were negative for E, EAC, and EA rosettes. She was treated for non-T, non-B CALLA-positive ALL and within 6 weeks was in a remission without evidence of cycling neutrophil counts. This young woman's case suggests that cyclic neutropenia may represent a previously unrecognized premalignant state associated with acute lymphoblastic leukemia.

Adult↗
PubMed1986

Selection of patients with Hodgkin's disease and non-Hodgkin's lymphoma for bone marrow transplantation.

Despite substantial progress in curative therapy of malignant lymphomas, some patients fail current treatment and die of refractory disease. Although Although high-dose chemotherapy and supralethal total body irradiation followed by bone marrow transplantation may salvage and cure a proportion of these refractory patients, treatment of such end-stage patients with marrow grafting often fails because of resistant disease or transplant-related complications. Using the analogy of transplantation in the early phases of acute and chronic leukemias, results of marrow transplant in Hodgkin's disease and non-Hodgkin's lymphoma might be improved if performed earlier in the course of the malignancy. The following collaborative report by the Seattle and Stanford groups examines current results of conventional lymphoma therapy to define subgroups of patients with "high-risk" lymphoma for whom early marrow transplant might be offered to control otherwise incurable disease.

Antibodies, Monoclonal↗
PubMed1986

Cure of malignant lymphoma in dogs with peripheral blood stem cell transplantation.

Twelve dogs with spontaneous malignant lymphoma in chemotherapy-induced remission were treated with total-body irradiation (TBI) and transplantation of autologous peripheral blood mononuclear cells collected following chemotherapy-induced expansion of the stem cell pool. Four animals (33%) died of transplant-related complications, five (41%) relapsed, and three (25%) are long-term disease-free survivors. Recovery to 1000 white cells/mm3 occurred by day 16 and dogs no longer required platelet transfusions by day 37. With the exception of delayed platelet recovery these results are virtually identical to those previously reported using autologous bone marrow transplantation for canine lymphoma. This study therefore suggests that autologous peripheral blood mononuclear cells collected following chemotherapy-induced expansion of the stem cell pool may offer a realistic alternative to autologous marrow transplantation in patients with malignant lymphoma for whom autologous marrow is not available.

Animals↗
PubMed1986

Interstitial pneumonitis following autologous bone marrow transplantation.

The incidence of interstitial pneumonitis (IP) was reviewed in 70 consecutive patients who received autologous marrow transplants for hematologic malignancies. All patients were treated with total-body irradiation (TBI), with or without other chemotherapeutic agents. Seven patients (10%) developed IP, 3 were due to cytomegalovirus, 1 due to Pneumomcystis carinii, and 3 of unknown cause (idiopathic). Risk factors for developing IP were increasing age and a prior history of irradiation to the chest. The use of methotrexate posttransplant did not increase the incidence of IP.

Adolescent↗
PubMed1986

Acute lymphoblastic leukaemia after bone marrow transplantation for aplastic anaemia.

An 11.5-year-old girl developed acute lymphoblastic leukaemia 7 months after bone marrow transplantation for severe aplastic anaemia. Before transplantation there were neither morphologic nor cytogenetic abnormalities to suggest preleukaemia. The conditioning regimen consisted only of cyclophosphamide. At the time of development of acute lymphoblastic leukaemia, chromosome analysis showed the blasts to be of host origin with clonal abnormalities including monosomy 7. Such a preleukaemic syndrome presenting as severe aplastic anaemia is a very rare event (the case reported here is the only one of 436 patients in Seattle) and cannot be reliably excluded before transplantation.

Acute Disease↗