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Biomedical subjects

L Acaba

Publications and source records attributed to L Acaba.

11 recordsLinked to original sources
PubMed1995

Abnormal liver function in patients undergoing autologous bone marrow transplantation for hematological malignancies.

Autologous bone marrow transplantation (AuBMT) is an accepted treatment modality for patients with high-risk or relapsed hematological malignancies. Hepatotoxicity, in particular veno-occlusive disease (VOD), is a significant complication of this therapy. The purpose of this study was to determine the clinical relevance of abnormal liver function in the patients who received high-dose cytotoxic therapy and AuBMT for hematological malignancies at Memorial Sloan Kettering Cancer Center. Medical records of 180 consecutive patients between 1984 and 1991 treated with cytotoxic chemotherapy and AuBMT for acute myelogenous leukemia, non-Hodgkin's lymphoma, and Hodgkin's disease were reviewed. Forty-six patients (26%) developed jaundice with bilirubin > 4 mg/dl. These patients had a 43% toxic death rate compared to an 11% toxic death rate in patients with lower bilirubins (p < 0.001). The main etiology of hyperbilirubinemia was VOD of the liver noted in 22 of the 180 patients (12%). Other etiologies of jaundice included hepatitis, sepsis with multiorgan dysfunction, cholecystitis, and recurrent disease. Hyperbilirubinemia of various etiologies is a significant complication of AuBMT. Several new strategies are under investigation to decrease the toxicity of intensive therapy.

Adolescent↗
PubMed1993

Dye-mediated photolysis is capable of eliminating drug-resistant (MDR+) tumor cells.

We evaluated the potential role of photoradiation therapy with a benzoporphyrin derivative, monoacid ring A (BPD-MA), and dihematoporphyrin ether (DHE), for the ex vivo purging of residual tumor cells from autologous bone marrow (BM) grafts. BPD-MA and DHE photosensitizing activity was tested against two human large-cell lymphoma cell lines and colony-forming unit-leukemia (CFU-L) derived from patients with acute myelogenous leukemia (AML). In mixing experiments, 4-log elimination of tumor cell lines was observed after 1 hour of incubation with 75 ng/mL of BPD-MA or 30 minutes of treatment with 12.5 micrograms/mL of DHE followed by white light exposure. By comparison, using the same concentration of BPD-MA, the mean recovery of normal BM progenitors was 4% +/- 0.8% (mean +/- SD) for granulocyte-macrophage colony-forming unit (CFU-GM) and 5% +/- 0.8% for burst-forming unit-erythroid (BFU-E). Similarly, DHE treatment resulted in the recovery of 5.2% +/- 2% and 9.8% +/- 3% of CFU-GM and BFU-E, respectively. Furthermore, equivalently cytotoxic concentrations of both DHE and BPD-MA and light were found not to kill normal pluripotent stem cells in BM, as demonstrated by their survival in two-step long-term marrow culture at levels equal to untreated controls. The T-lymphoblastic leukemia cell line CEM and its vinblastine (VBL)-resistant subline CEM/VBL, along with the acute promyelocyte leukemia cell line HL-60 and its vincristine (VCR)-resistant subline HL-60/VCR, were also tested. BPD-MA at 75 ng/mL was able to provide a greater than 4-log elimination of the drug-sensitive cell lines, but only a 34% and 55% decrease of the drug-resistant HL-60/VCR and CEM/VBL cell lines, respectively. On the contrary, 12.5 micrograms/mL of DHE reduced the clonogenic growth of all the cell lines by more than 4 logs. Further experiments demonstrated decreased uptake of both BPD-MA and DHE by the resistant cell lines. However, all the cell lines took up more DHE than BPD-MA under similar experimental conditions. Our results demonstrate the preferential cytotoxicity of BPD-MA and DHE toward neoplastic cell lines and CFU-L from AML patients. In addition, DHE was slightly more effective in purging tumor cells expressing the p-170 glycoprotein. These results suggest that photoradiation with DHE would be useful for in vitro purging of residual drug-resistant leukemia and lymphoma cells.

Bone Marrow↗
PubMed1993

Rationale for purging in autologous stem cell transplantation.

The success of autologous stem cell transplantation using bone marrow or peripheral blood stem cells depends not only on in vivo irradication of the disease by cytotoxic therapy but also on complete hematopoietic engraftment with no risk of relapse from the infused cells. Various methods are available for removing (purging) such contaminants. Purging techniques were developed by use of various in vitro models utilizing cell lines and fresh cancer cells. Once effective conditions were developed, they were advanced onto clinical trials. Various approaches for purging have been used. Subgroups of leukemia and lymphoma have now shown clinical benefit by the use of purged stem cells. Emphasis is now being placed on utilizing the information already obtained by the pre-clinical investigators on designing better clinical trials.

Animals↗
PubMed1993

Improving the role of hematopoietic support for high-dose cytotoxic therapy.

Dose intensification of cytotoxic drugs is now being evaluated in several trials. Various methods are available to manage the hematopoietic toxicity. Hematopoietic growth factors can be used alone and/or in combination with hematopoietic stem cell rescue. Patients undergoing autologous stem cell transplantation (AuSCT) have their own bone marrow and/or peripheral blood used for hematopoietic engraftment. In several malignancies, the bone marrow is involved with tumor, and in such situations, the success of AuSCT may improve if hematopoietic elements are enriched (positive selection) or if contaminating cancer cells are purged by negative selection. In patients undergoing allogeneic bone marrow transplantation, T lymphocytes, from donor cells, contribute to the development of graft-versus-host disease (GVHD), which can result in major morbidity and mortality. The incidence of GVHD has decreased with selective purging of T lymphocytes, but further modifications are needed to improve hematopoietic engraftment. Methods for purging hematopoietic stem cells are discussed, with emphasis on the therapeutic role of purging. Growing stem cells from a small amount of bone marrow presents a new possibility. Furthermore, genetic engineering can enhance immune surveillance and decrease drug resistance. Analysis of the clinical trials utilizing various doses of cytotoxic therapy with proper methods of hematopoietic rescue will help avoid unnecessary dose escalation and help decide the optimum use of cancer treatment modalities.

Antineoplastic Agents↗
PubMed1992

Purging in autologous and allogeneic bone marrow transplantation.

The success of hematoablative dosages of cytotoxic therapy followed by stem cell transplantation depends on the disease response to the intensive drug dose and the ability of the transplant to provide durable hematopoietic reconstitution. In autologous stem cell transplantation, patients' own bone marrow or peripheral blood is used for hematopoietic engraftment. In several diseases the bone marrow is involved, and in such situations, the success of autologous stem cell transplantation may improve if the hematopoietic elements are enriched (positive selection) or if the contaminating cancer cells are purged by negative selection. In patients undergoing allogeneic bone marrow transplantation, the T lymphocytes of the donor cells contribute to the development of graft-versus-host disease with significant morbidity and mortality. Selective purging of T lymphocytes has dramatically decreased the incidence of graft-versus-host disease. In this paper, various methods for purging hematopoietic stem cells are detailed with emphasis on treatment planning. Exciting new possibilities include growing stem cells from a small amount of bone marrow, enhancing immune surveillance, and decreasing drug resistance by genetic engineering.

Animals↗
PubMed1992

Treatment of patients with relapsed and resistant non-Hodgkin's lymphoma using total body irradiation, etoposide, and cyclophosphamide and autologous bone marrow transplantation.

PURPOSE: Patients with non-Hodgkin's lymphoma (NHL) who do not achieve a complete response (CR) after induction chemotherapy or who relapse after achieving a CR are rarely cured of their disease by the usual salvage therapy. Success of high-dose cytotoxic therapy with an autologous bone marrow transplant (AuBMT) is limited. We describe the results of a prospective single-institution study using a new conditioning regimen for patients with relapsed or resistant NHL who underwent AuBMT. PATIENTS AND METHODS: Forty-four patients were reinduced with cytotoxic therapy and then evaluated for response. All patients received the conditioning regimen of hyperfractionated total body irradiation (TBI), etoposide (VP-16), and cyclophosphamide (CTX) followed by autologous bone marrow reinfusion. RESULTS: The disease-free survival (DFS) rate was 57% with a median follow-up of 42+ months. The only variable significantly associated with DFS was the patient's remission status at AuBMT. Patients who underwent AuBMT in CR had a DFS of 80%, whereas patients who underwent AuBMT in partial response (PR) or with progressive disease (PD) had a DFS of 60% and 11%, respectively (P = .002). The major toxicity was hemorrhage at the site of bulky disease, especially in patients with residual mediastinal and/or pulmonary disease. CONCLUSION: Planned reinduction cytotoxic therapy followed by TBI, VP-16, and CTX with AuBMT is an effective treatment for patients with relapsed and resistant NHL.

Adult↗
PubMed1992

Autologous bone marrow transplantation for acute myelogenous leukemia using 4-hydroperoxycyclophosphamide and VP-16 purged bone marrow.

Thirty adult patients with acute myelogenous leukemia (AML) in remission were treated with hyperfractionated total body irradiation, VP-16, and cyclophosphamide followed by infusion of autologous bone marrow purged with 4-hydroperoxycyclophosphamide and VP-16. Fifteen patients were transplanted in first remission (R1), 13 in second remission (R2), and two in third remission (R3). All patients had hematopoietic engraftment. The median time to achieve a white blood cell count of 1.0 x 10(9)/l and a neutrophil count of 500 x 10(6)/l was 32 days. The median time to achieve an unsupported platelet count of 50 x 10(9)/l was 70 days. There were four transplant-related deaths, all in patients in R2. Ten patients have relapsed, including both patients transplanted in R3. The disease-free survival (DFS) of all patients is 52%, median follow-up not yet reached. Although the number of patients in each group is small and follow-up is limited, there is a trend toward improved actuarial DFS in patients transplanted in R1 compared with patients transplanted in R2 (72 vs 39%; p = 0.081). Use of VP-16 in the conditioning regimen as well as in the purging procedure is feasible in the treatment of patients with AML.

Adult↗
PubMedDate not supplied

Simultaneous occurrence of Hodgkin's disease and chronic lymphocyte leukemia: a unique presentation.

Chronic lymphocytic leukemia (CLL) is a chronic, low-grade hematologic malignancy that can transform to a large cell non-Hodgkin's lymphoma (Richter's syndrome), which is associated with an unfavorable prognosis. A distinct Hodgkin's disease subgroup of lymphomatous CLL transformation has been well characterized. We describe a patient presenting with simultaneous manifestations of CLL and Hodgkin's disease. This patient is unique, presenting with separate sites of involvement of each disease within the same organ, in this case the bone marrow. The morphologic and immunohistochemical findings at diagnosis are correlated with the findings of the postmortem examination.

Autopsy↗
PubMedDate not supplied

Excellent response to interferon therapy in a patient with hypereosinophilic syndrome and elevated serum immunoglobulin E levels.

The hypereosinophilic syndrome (HES) is a heterogeneous disease characterized by sustained eosinophilia for a period of at least six months with evidence of organ involvement. Its manifestations range from a benign disorder not requiring any therapy to an aggressive, malignant variety refractory to common treatments. Diverse therapies have been used, including steroids, hydroxyurea, and chemotherapy, with variable responses. Recently alpha-interferon therapy has been shown effective in this disorder. Of the various prognostic factors, elevated serum immunoglobulin E (IgE) levels is considered among the most favorable, with most patients presenting with a "benign" disorder, not requiring therapy. We describe a patient presenting with an aggressive variant of HES despite having elevated IgE levels. The patient had a dramatic and lasting response to alpha-interferon.

Adult↗