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Biomedical subjects

S Bulova

Publications and source records attributed to S Bulova.

13 recordsLinked to original sources
PubMed1996

Unrelated donor bone marrow transplantation without T cell depletion using a chemotherapy only condition regimen. Low incidence of failed engraftment and severe acute GVHD.

Twenty-five patients with hematologic malignancies were treated with busulfan (16 mg/kg) and cyclophosphamide (50 mg/kg x 3 days) as conditioning for bone marrow transplantation using marrow from serologically matched, DR locus genotypically identical unrelated donors. Previous studies of BuCy2 as conditioning for UD-BMT have reported a graft failure rate of up to 21% suggesting it may be insufficiently immunosuppressive in this setting. We elected not to use BuCy4 as it may have a higher incidence of extramedullary toxicity. In addition the patients received GM-CSF (500 mg/m2) from day 0, cyclosporine and short-course methotrexate (15 mg/m2 x 1, then 10 mg/m2 x 3) as GVHD prophylaxis and prophylactic ganciclovir at engraftment if either they or their donor were CMV antibody positive. The median age of the 25 patients was 41 years and the most common diagnosis was CML (76%). Seven patients were considered poor risk and eight males were recipients of marrow from female donors. Sixteen patients survive at a median of 435 days from transplant. The actuarial overall and disease-free survivals at 1 year in this group of older patients were 62 +/- 20% and 57 +/- 20% and 100-day survival was 70%. The engraftment rate was 100%; there have been no instances of secondary graft failure. Fifteen patients (60%) developed grade II-IV GVHD and 12 of 16 (75%) developed some chronic GVHD but only half of these were extensive. The performance status of survivors is good (median of 90); seven of 12 eligible patients are back at work. This study demonstrates that UD-BMT can be successfully performed in very closely HLA-matched older patients using a chemotherapy-only protocol and that low rates of severe acute GVHD can be achieved without T cell depletion.

Actuarial Analysis↗
PubMed1995

Extramedullary toxicity of a conditioning regimen containing busulphan, cyclophosphamide and etoposide in 84 patients undergoing autologous and allogenic bone marrow transplantation.

Relapse is still a common problem after bone marrow transplant (BMT) and teh value of adding etoposide to standard conditioning agents is being tested. The aim of the study was to assess the extramedullary toxicity which resulted from adding etoposide to busulphan 16 mg/kg and cyclophoshamide 120 mg/kg (BuCY2). Eighty four patients received etoposide 40 mg/kg in addition to BuCY2 as conditioning for autologous and allogeneic BMT for leukemia and lymphoma. The Bearman system of grading extramedullary toxicity was used along with a system of grading skin toxicity that we devised. There were seven acute toxic deaths (8%) and in total 15 patients experienced life-threatening or fatal toxicity. The major finding was a striking increase in pulmonary toxicity with six deaths (five alveolar hemorrhage and one pulmonary embolus). Five of seven of the patients with severe pulmonary toxicity had been given irradiation to the lung fields (P < 0.001). Thirty nine per cent of patients had veno-occlusive disease of the liver but the case fatality rate was low (1 of 33). Dermatologic toxicity was experienced by 82% of patients and was symptomatically troublesome but rapidly reversible. The addition of etoposide to BuCY2 increases non-hematological toxicity. This regimen is associated with severe pulmonary toxicity in patients with a history of prior chest irradiation. A high incidence of skin toxicity was seen; a system for describing this toxicity is proposed.

Adolescent↗
PubMed1992

Syngeneic marrow transplantation in multiple myeloma.

Two cases of IgA multiple myeloma treated with syngeneic bone marrow transplant and a non-total body irradiation (TBI) conditioning regimen are reported. Both patients presented with stage III disease which responded to standard chemotherapeutic management. The myelo-ablative program for transplant consisted of busulfan and cyclophosphamide (Bu/Cy). Evaluation at 40 days post-transplant revealed no evidence of residual myeloma in either patient. One patient died of disseminated Aspergillus fumigatus at day 73 post-transplant. The other patient relapsed at 18 months post-transplant. This conditioning regimen shows efficacy in aggressive myeloma and could be considered earlier in the disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Transient high grade heart block following autologous bone marrow infusion.

We performed a retrospective analysis of 42 consecutive patients undergoing autologous BMT to determine the incidence of second and third degree heart block following the infusion of cryopreserved autologous bone marrow and to identify any predisposing characteristics. A decrease in heart rate > or = 10 beats/min was observed in 80.5% of patients, with a mean decrement of 27 +/- 7 beats/min. 48.8% of patients developed absolute bradycardia (< or = 60 beats/min). Four of 41 patients (9.7%) experienced high-grade heart block: 9.7% second degree and 4.8% third degree. Heart block patients did not differ from the non-heart block group with respect to age, interval from diagnosis or bone marrow harvest to transplant, cardiac risk factors, pretransplant electrocardiograms or radionuclide angiograms, transplant chemotherapy regimens or serum chemistry values. There was an increased incidence of heart block in patients with prior exposure to cyclophosphamide (p < 0.05) and vinca alkaloids (p < 0.05). There appears to be a high incidence of transient second and third degree heart block following autologous marrow infusion. This may be related to prior chemotherapy, but more likely is an effect of the infusate itself. Predisposing factors were not identified.

Adolescent↗
PubMed1991

High-dose cytosine arabinoside and etoposide in the treatment of relapsed or refractory adult leukemia.

Thirteen patients with leukemia were treated with a combination of cytosine arabinoside (ara-C) (3 g/m2 by 1-h infusion every 12 h for 12 doses) and etoposide (100 mg/m2 daily over 1 h for 3 doses). Toxicity of the regimen consisted of severe hematologic suppression, moderate abdominal colic with vomiting and diarrhea, and occasionally severe central nervous system (CNS) toxicity. Two patients received the regimen as consolidation for acute myelogenous leukemia in remission. Of the remaining 11 patients with chronic myeloid leukemia (CML)-blast crises or relapsed/refractory acute myeloid leukemia (AML), nine patients (82%) obtained CR (or chronic phase) and two patients obtained partial remission (PR). High-dose ara-C and etoposide is an effective but toxic regiment for the treatment of relapsed or refractory myeloid leukemias.

Adult↗
PubMed1991

Autologous bone marrow transplantation for advanced stage mycosis fungoides.

Patients with advanced stage cutaneous T cell lymphoma (CTCL) have a median survival of 2-5 years with no currently available curative therapy. This limited pilot study was performed to determine if CTCL patients could undergo autologous bone marrow transplantation (ABMT) as a curative treatment without developing life-threatening infections. Since selection of a chemotherapeutic regimen is essentially empirical at this time, several drug combinations were screened. Total skin electron beam radiotherapy was used prior to transplantation to control the skin disease of four patients. Six patients have been transplanted and all have engrafted normally. Infections that developed after transplantation responded to conventional therapy and were typical of those observed in other patients undergoing ABMT. Five of the six patients had a complete clinical response to ABMT but three of these responses lasted less than 100 days. Two recent patients who were treated with carmustine, etoposide, and cisplatin are alive more than 1 year after transplantation without evidence of active disease. Thus, although this study does not prove the efficacy of ABMT, it does demonstrate that patients with CTCL can undergo ABMT without developing life-threatening infections and that carmustine-etoposide-cisplatin plus ABMT should be evaluated in subsequent studies to treat patients with poor prognosis CTCL.

Adult↗
PubMed1990

Frequency of veno-occlusive disease of the liver in bone marrow transplantation with a modified busulfan/cyclophosphamide preparative regimen.

Veno-occlusive disease (VOD) of the liver is a major complication of bone marrow transplantation (BMT). The overall frequency of VOD has ranged from 20 to 30%, with a mortality rate greater than 40%, as reported by centers utilizing cyclophosphamide (Cy) and total body irradiation (CyTBI) or various chemotherapeutic regimens, including the busulfan (Bu) (4 mg/kg for 4 days) and Cy (50 mg/kg for 4 days) (BuCy4) combination. Since 1986, Hahnemann University (HU) has primarily used the BuCy2 regimen, i.e., Bu (4 mg/kg for 4 days) followed by Cy (60 mg/kg for 2 days). We reviewed 74 consecutive patients who received either an autologous or allogeneic BMT for various malignancies from January 1986 through October 1988 to determine the frequency of VOD. Seven of 74 consecutive patients met clinical criteria for VOD, for a total frequency of 9.5%. Fifty-five patients were conditioned with various other regimens. Only 5 of the patients conditioned with BuCy2 developed VOD (9.1%). This is less than the 25% reported frequency of VOD in patients who received CyTBI (1,000 rads) and less than the 24% reported frequency of VOD in patients who received BuCy4. Only one of seven patients who developed VOD died from the disease. One patient died of sepsis after the VOD had almost completely resolved. The remaining five completely recovered. We conclude that the total Cy dose, and not Bu, is the major factor in the occurrence of VOD in Bu/Cy BMT preparative regimens, and the BuCy2 regimen reduces the frequency of VOD in autologous and allogeneic graft recipients when compared to CyTBI or the BuCy4 regimens.

Adolescent↗
PubMed1990

Bone marrow transplantation following busulfan and cyclophosphamide for acute myelogenous leukemia.

Twenty-five consecutive patients with acute myelogenous leukemia (AML) underwent 26 allogeneic bone marrow transplants at Hahnemann University Hospital. Marrow ablation for all patients consisted of busulfan 16 mg/kg and cyclophosphamide 120 mg/kg (BUCY2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methylprednisolone. Seventeen transplants were performed during first remission and the rest during subsequent remission or relapse. All patients engrafted and all but one achieved a complete remission (CR) following a short period of aplasia. Twenty-two of 25 patients are alive. All 17 patients with AML transplanted in first CR are alive and 15 of these patients are in sustained hematologic remission with an estimated 2-year disease free survival of 85%. The estimated 2-year disease free survival is 70% for all patients followed for a median of 622 days (range 134-1533). Acute GVHD of grades 2-4 occurred in 23% of these patients. Toxicities of the regimen including interstitial pneumonitis, veno-occlusive disease (VOD) and hemorrhagic cystitis were minimal. There were no treatment related deaths. These results demonstrate that BUCY2 should be considered as a preparative regimen for allogeneic bone marrow transplantation for patients with AML in first remission.

Adolescent↗
PubMed1983

4'-(9-acridinylamino)methane-sulfon-m-anisidide (m-AMSA) and 5-azacytidine (AZA) in the treatment of relapsed adult acute leukemia.

Between March 1980 and December 1981, 22 patients were treated with 4'(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and 5-azacytidine (AZA), each given by I.V. push in a dosage of 150 mg/m2 for 5 days. Seven of 12 prior-remitting, acute nonlymphoblastic leukemia (ANLL) patients achieved complete remission (58%). Six ANLL patients who failed to remit on standard daunorubicin-cytosine arabinoside programs also failed to remit on the m-AMSA-AZA combination. Two patients with relapsed acute lymphatic leukemia (ALL) also failed while two patients with chronic myelocytic leukemia (CML) in evolution were cytoreduced. The seven patients who achieved remission had additional relapse-free survival for a median of six months (range 1-23+ months). One patient obtained a second remission with m-AMSA-AZA after relapse which followed a 9-month period of nonmaintained remission. Most patients demonstrated mild to moderate nausea and vomiting. Hepatic toxicity was mild to infrequent. Only four patients showed cardiac toxicity which was not life-threatening. The most troublesome toxicity was mucositis and was seen in 11 patients; four whom required I.V. hyperalimentation. We conclude that this combination is an effective salvage program for relapsed prior-remitting ANLL. Future studies should be conducted in three areas. The first study might be a comparison of relapsed prior-remitting ANLL with single-agent m-AMSA. The second, in untreated ANLL, following induction with DAT, might use m-AMSA-AZA in consolidation and maintenance arms of future protocols. The final study should explore m-AMSA-AZA activity in evolved CML in a greater number of patients.

Acute Disease↗