asta-z-7557 and Acute-Disease

Fourteen adult patients in first complete remission of acute leukemia (A.L.) [6 with acute lymphoblastic leukemia (ALL), 8 with acute non lymphoblastic leukemia (ANLL)] were consolidated with high dose cyclophosphamide and total body irradiation followed by autologous bone marrow transplantation (ABMT) with marrow cleansed in vitro by Asta Z 7557. According to our previously described protocol showing evidence for a wide range of sensitivity from patient to patient, the marrow of each individual patient was incubated with the highest tolerable dose of Asta Z 7557. This dose, individually determined, was defined as the dose sparing between 0 and 10% of CFU-GM (CFU-GM DL95). ABMT was not followed by maintenance therapy. Hematological reconstitution was significantly faster in ALL patients when compared to ANLL patients. Out of these 14 patients: 2 relapsed on months 5 and 15 respectively after ABMT, and 2 died in complete remission on months 3 and 16 respectively, of veno-occlusive disease and encephalitis. Ten patients (70%) remain in complete remission up to a median of 15 months +, with 4 patients over 24 months +.

Topics: Acute Disease; Adult; Bone Marrow; Bone Marrow Transplantation; Combined Modality Therapy; Cyclophosphamide; Female; Humans; Leukemia; Male; Middle Aged

The lymphocyte subset reconstitution after high-dose chemotherapy and total body irradiation followed by autologous bone marrow transplantation (ABMT) has been studied in ten patients with acute leukemia (AL) (6 ALL and 4 ANLL) in complete remission (CR). Bone marrow was treated in vitro with high-dose ASTA Z 7557, individually determined according to CFU-GM sensitivity. The different peripheral blood lymphocyte subsets were characterized by means of monoclonal antibodies (indirect immunofluorescence assay) belonging to the following classes of differentiation: OKT11-T11 (CD2), OKT3-T3 (CD3), OKT4-T4 (CD4), OKT8-T8 (CD8), OKIal-I2 (HLA-DR), Leu7 (natural killer/killer) and by means of polyspecific antiimmunoglobulin sera (direct immunofluorescence assay). Data in these ten patients were compared with those of a control group of 21 normal donors and with a control group of 14 patients in CR without ABMT. Our results showed a marked depression of the T4:T8 ratio in patients with AL before ABMT, compared with normal donors who had respective values of 1.02 and 1.33 (p less than 0.01). This depression was increased and prolonged up to day 515 after ABMT, with a value of 0.32 (p less than 0.01 compared with the pregraft situation; p less than 0.001 compared with normal donors). This T4:T8 ratio imbalance was related to the depletion of the T4+ population and to the increase of the T8+ subset. This imbalance was emphasized after ABMT. The Leu 7+ population was also increased in grafted patients compared with normal donors (p less than 0.01). The B-cell population remained unchanged throughout the study. We conclude that patients autografted with marrow treated in vitro by high-dose ASTA Z 7557 may experience a long-term T-cell subset imbalance.

Topics: Acute Disease; Adult; Bone Marrow; Bone Marrow Transplantation; Cyclophosphamide; Female; Humans; Killer Cells, Natural; Leukemia; Lymphocytes; Male; T-Lymphocytes; Transplantation, Autologous

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%).

Topics: Acute Disease; Bone Marrow; Bone Marrow Transplantation; Cell Separation; Colony-Forming Units Assay; Cyclophosphamide; Freezing; Humans; In Vitro Techniques; Leukemia; Tissue Preservation; Transplantation, Autologous

Topics: Acute Disease; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Leukemia