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Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 379 records · Page 21Linked to original sources

Autologous bone marrow transplantation using marrow incubated with Asta Z 7557 in adult acute leukemia.

The sensitivity of human myeloblastic leukemic (CFU-L) and normal hemopoietic stem cells (CFU-GM and BFU-e) to Asta Z 7557 (INN Mafosfamide) was studied with regard to autologous bone marrow transplantation (ABMT) with cleansed marrow for consolidation therapy in adult patients with acute leukemia (AL) in remission. Establishment of the dose-response curves for CFU-GM (n = 37), BFUe (n = 11), and myeloblastic CFU-L (n = 9) demonstrated a wide range of sensitivity from patient to patient for all three progenitors. Whereas CFU-L, CFU-GM, and BFU-e grown in semisolid cultures disclosed similar sensitivities to Asta Z 7557, long-term culture (LTC) studies (n = 41) indicated a higher resistance of early progenitors. In an effort to achieve a maximum tumor cell kill and yet spare a sufficient amount of normal stem cells to ensure consistent engraftment, we defined the optimal dose for marrow cleansing as the dose sparing 5% CFU-GM (LD95). This dose was established from a preincubation test (PIT) realized on a 10-mL marrow aspirate taken 15 days before marrow collection in each individual patient. Twenty-four adult patients while in remission of AL (20 in complete remission, four in partial remission) were consolidated by cyclophosphamide 60 mg/kg X 2 and total body irradiation at 10 Gy followed by ABMT with marrow cleansed by Asta Z 7557 according to the specification described above. Patients were divided in two groups: group 1, unfavorable prognosis (11 patients); group 2, standard prognosis [13 patients in first complete remission (CR)]. All patients engrafted on leukocytes (median day for recovery to 10(9)/L: day 30), patients with ALL recovered faster than patients with ANL (median day 19 v 34). Similarly, recovery of platelets to 50.10(9)/L occurred sooner in patients with ALL (median day 67, range day 23 through 90) whereas three patients with acute nonlymphoblastic leukemia (ANLL) in group 2 had to be supported with platelet transfusions for more than one year. In group 1, six patients had recurrent tumor within six months; three patients died from toxicity with no evidence of tumor. Two patients are still disease-free with a short follow-up (nine and ten months). In group 2, two patients died from toxicity with no evidence of leukemia three and 16 months post-ABMT. One patient with a M5 ANLL and one patient with ALL relapsed at six and 15 months, respectively. Nine patients have remained in CR or are disease-free with a median follow-up of 22 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Recovery of CFU-GM from cryopreserved marrow and in vivo evaluation after autologous bone marrow transplantation are predictive of engraftment.

In 18 patients with non-Hodgkin's lymphomas or solid tumors treated with intensive chemotherapy and/or total-body irradiation followed by autologous bone marrow transplantation (ABMT), we assessed the value of granulocyte-macrophage progenitor cells (CFU-GM) monitoring to predict engraftment. We studied CFU-GM in cryopreserved marrow and attempted to settle whether detection of CFU-GM in vivo after ABMT has a predictive value on engraftment. Our data showed: The absence of linear correlation linking recovery of hematopoiesis to the dose of CFU-GM/kg infused. The existence of a CFU-GM threshold in respect to engraftment. Patients receiving doses of CFU-GM greater than 10(3)/kg had significantly faster recovery kinetics for hematopoiesis than did patients receiving doses below this threshold, with median recoveries to 0.5 and 1.0 X 10(9) neutrophils/liter, respectively, on days 14 and 15 versus days 29 and 31.5 (p less than 0.05 and p less than 0.02) and median recoveries to 1.0 and 2.5 X 10(9) leukocytes/liter respectively, on days 12.5 and 16 versus days 28 and 30.5 (p less than 0.05 and p less than 0.02). Considering the entire course of events during the first four weeks, we were able to show that white blood cell recovery was significantly faster in the group of patients receiving doses of CFU-GM greater than 10(3)/kg (p less than 0.001). Sequential studies of the reappearance of CFU-GM in marrow and peripheral blood indicated that the kinetics of CFU-GM recovery in vivo after ABMT predict engraftment. By day 7 after the graft, CFU-GM were already detectable in the marrow at a level of 10% of the dose infused for patients with optimal engraftment--median time to recovery to 1.0 and 2.5 X 10(9) leukocytes/liter and 1.0 X 10(9) neutrophils/liter on days 11, 15, and 14.5 versus days 18, 23, and 23 (p less than 0.02, less than 0.05, and less than 0.05), respectively after. On day 10 after ABMT, a 15% CFU-GM level in bone marrow confirmed engraftment, with a significant correlation of all parameters studied--1.0 and 2.5 X 10(9) leukocytes/liter (p less than 0.02 and less than 0.01), 0.5 and 1.0 X 10(9) neutrophils/liter (p less than 0.05), 50.0 and 100.0 X 10(9) platelets/liter (p less than 0.05). On day 14, a 50% CFU-GM level was reached in all patients with optimal engraftment; p less than 0.01 on 1.0, and 2.5 X 10(9) leukocytes on 0.5 and 1.0 X 10(9) neutrophils/liter. The detection of circulating CFU-GM in the blood by day 10 or 14 indicated engraftment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Autologous marrow transplantation for patients with chronic myeloid leukemia in accelerated or blastic phase: report of 14 cases.

Between June 1979 and October 1983, 14 autografts were performed in 13 patients with CML (ten blast crisis, four accelerated phase). Results were disappointing: four patients died during aplasia; seven returned to chronic phase, but three died of hemorrhage, four relapsed, and three did not reverse. The main problem was the very low rate of successful engraftment. Both the collection of bone marrow after treatment with busulfan and a particular sensitivity of CFU-GM to cryoinjury were responsible for the infusion of very low doses of CFU-GM. However, we observed some promising results: In one patient in acute blast crisis, the Ph 1 chromosome disappeared, as well as the cytogenetic marker of transformation; in another patient with acute pure cytogenetic acceleration, the abnormal clone disappeared for 27 months; a third patient was maintained in a second chronic phase for 20 months. Thus we suggest that the results of autografting in chronic myeloid leukemia would be improved by infusing the largest possible dose of stem cells collected before or long after treatment by busulfan, and freezing them following a careful program.

Adult↗

[Autograft of bone marrow treated by immunotoxin T 101 for the treatment of T-cell leukemia and lymphoma. Initial clinical cases].

In order to consolidate a complete or partial remission, 4 patients with T-cell malignancy received cyclophosphamide 120 mg/kg plus total body irradiation, followed by reinfusion of cryopreserved autologous bone marrow purged in vitro by the immunotoxin T 101 (SR 41322) composed of the murine monoclonal T 101 antibody coupled with the A chain of ricin. The immunotoxin was applied in doses of 10(-9) and 10(-8) M for periods of 4 and 20 hours at 37 degrees C. The recovery of CFUc and BFUe progenitors was total following incubation with IT 101, but reduced after cryopreservation (1-15 to 80% for CFUc,-33 to 47% for BFUe), haematopoietic recovery occurred within normal delays, demonstrating that autologous bone marrow pretreated with the immunotoxin can be successfully transplanted. However, the slow increase in lymphocytes and the occurrence of lethal infection in 2 cases indicate that an in-depth study of immunological reconstitution after in vitro treatment of bone marrow with ITT 101 is necessary.

Adolescent↗

Effects of dipropylacetate on the glycine cleavage enzyme system and glycine levels. A possible experimental approach to non-ketotic hyperglycinemia.

The effect of chronic administration of the anticonvulsive drug di-n-propylacetate (DPA) on the glycine cleavage enzyme system was studied. Glycine concentrations were monitored in blood, liver, brain and spinal cord of 10-day-old rats. DPA treatment decreases glycine cleavage activity by approximately 50% in liver, and 35% in brain. The decreased cleavage activity correlates with an increase of glycine levels in blood, liver and brain. Failure to cleave glycine characterizes a metabolic disorder known as non-ketotic hyperglycinemia, which is associated with elevated concentrations of glycine in biological fluids. The inhibitory effect of DPA may provide an experimental approach to study the biochemical and pathogenic mechanisms of non-ketotic hyperglycemia.

Age Factors↗

Cyproterone acetate in the treatment of metastatic cancer of the male breast.

Ten male patients with advanced cancer of the breast were treated with cyproterone acetate, an anti-androgenic compound with additional progestational properties. Seven patients achieved a response, for a median duration of 8 months. Plasma testosterone and estradiol levels fell significantly during therapy, but quantitatively this drop was not related to the therapeutic response. Cyproterone acetate is an effective and well-tolerated treatment for metastatic male breast cancer.

Aged↗

Epirubicin in non-Hodgkin's lymphomas.

Epirubicin (Epi-DX), a new analog of doxorubicin, was administered I.V. once q 3 weeks at the dose of 90 mg/m2 to 20 evaluable patients with non-Hodgkin's lymphomas (NHL). Eighty-two percent of patients with favorable histology and 67% with unfavorable histology achieved complete or partial remissions, with an overall response rate of 75%. Gastrointestinal and hematologic toxicity was generally mild to moderate. Reversible ST-T changes were observed only in two patients. Epi-DX has high activity in patients with NHL, and further studies in combination with other agents are recommended.

Adult↗

Standardization and characterization of the procedure for in vitro treatment of human bone marrow with cyclophosphamide derivatives.

Thirty human bone marrow (BM) suspensions from patients with acute leukaemia patients in remission were processed with the Haemonetics 30 flow cell separator in order to separate buffy-coats and to treat them in vitro with a derivative of cyclophosphamide (ASTA Z 7557). After processing, the volumes of BM suspensions were reduced to 25%. Recoveries of leucocytes, CFUc and BFUe were respectively 62, 85 and 84%. In vitro treatment with doses of ASTA Z ranging from 50 to 140 micrograms/2 X 10(7) leucocytes (according to the CFUc sensitivity of each patient) destroyed 95 +/- 5% of initial CFUc. After freezing and thawing, recovery of CFUc from treated BM was poor (24%) in comparison to that obtained with untreated BM (79%).

Acute Disease↗

Childhood abnormal expansion of large granular lymphocytes.

An expansion of large granular lymphocytes (LGL) in the peripheral blood (PB) of a 10-year-old child is described. After a long history of uncertain hematological diagnosis and chemotherapeutic regimens and 2 years after any kind of therapy, the child showed in PB an expansion of LGL E-rosette+, OKT3+, OKT8+, Leu7+. Cytotoxic activities showed high natural killer activity and an increase of PHA-induced cytotoxicity. Histological findings in the spleen, abdominal lymph nodes and bone marrow excluded a lymphoproliferative disease, but liver biopsy revealed a chronic aggressive hepatitis.

Bone Marrow Examination↗

Chemotherapy in metastatic male breast cancer.

14 male patients with metastatic breast cancer received a total of 20 chemotherapeutic trials with 2 basic combination regimens, namely, variants of the Cooper's regimen CMFVP and adriamycin-containing combinations. Overall, a 35% response rate was observed. Our data suggest that cancer of the breast in the male is responsive to the same combinations used in the female, with regimens including adriamycin being probably superior to regimens without it.

Adult↗

Hormonal treatment of disseminated male breast cancer.

14 males with disseminated cancer of breast received a total of 35 endocrine trials, mainly in the form of hormonal supplementation. Overall, a 43% response rate was observed. In particular, remissions occurred in 7 of 11 instances with cyproterone acetate, in 3 of 7 with tamoxifen, in 2 of 5 with estrogens, in 2 of 5 with aminoglutethimide, in none of 3 with high-dose medroxyprogesterone acetate, in none of 1 with androgens, and in 1 of 3 with castration. The response to additive hormonal therapy was 44%. Median overall response duration was 10 months, 11 months following additive hormonal therapy. Median survival from start of therapy was longer in responding than in nonresponding patients (23.5 vs. 11 months). A disease-free interval did not appear to influence hormonal response. Patients responding to one form of hormonal treatment had a greater likelihood of responding to subsequent hormonal manipulations. Additive hormonal therapy may provide effective palliation in males with advanced breast cancer, and should be considered as a valid alternative to orchiectomy.

Adult↗