scholarly journals Correlation of occult clonogenic leukemia drug sensitivity with relapse after autologous bone marrow transplantation

Blood ◽  
1991 ◽  
Vol 78 (4) ◽  
pp. 1125-1131 ◽  
Author(s):  
CB Miller ◽  
BA Zehnbauer ◽  
S Piantadosi ◽  
SD Rowley ◽  
RJ Jones
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Therapeutic Results ◽  
Autologous Bone ◽  
Minimal Residual

Abstract Despite initial complete remission rates exceeding 70%, the majority of patients with acute myeloid leukemia (AML) and adults with acute lymphocytic leukemia (ALL) eventually relapse. Improving the therapeutic results in acute leukemia requires detecting, and understanding the biology of, the minimal residual leukemia remaining after therapy and responsible for relapse. To investigate the biologic relevance of an in vitro assay for clonogenic leukemia (leukemia colony- forming units [CFU-L]) as a measure of minimal residual leukemia, we studied 58 consecutive patients with acute leukemia in complete remission undergoing autologous bone marrow transplantation (BMT) with cyclophosphamide-based therapy. CFU-L were cultured from the pretransplant remission marrows in 45 of 58 patients: 35 of 43 patients with AML and 10 of 15 with ALL. Clonal rearrangements, identical to the patients' overt leukemia when available, were detected in the occult CFU-L from four of the eight patients with ALL in whom adequate DNA for analysis could be obtained from the CFU-L. None of the uncultured pretransplant remission marrows from the 15 ALL patients showed clonal gene rearrangements. We also determined the in vitro sensitivity of the occult CFU-L to 4-hydroperoxycyclophosphamide (4HC), and correlated these results with the outcome of the patients. The sensitivity of the occult CFU-L to 4HC was the only factor that predicted relapse following BMT. The actuarial probability of relapse was 18% in the 23 patients whose CFU-L were sensitive to 4HC compared with 77% in the 22 patients whose CFU-L were resistant (P less than .001). The only factor that influenced the CFU-L sensitivity to 4HC was the type of leukemia. The CFU-L from the AML patients were more sensitive to 4HC than the CFU- L from the ALL patients (P = .001). Occult CFU-L genetically and functionally represent occult leukemia. Therefore, the CFU-L assay should provide a means for studying the biology of minimal residual leukemia and improving the therapeutic results in patients with acute leukemia.

scholarly journals Correlation of occult clonogenic leukemia drug sensitivity with relapse after autologous bone marrow transplantation

Blood ◽  
1991 ◽  
Vol 78 (4) ◽  
pp. 1125-1131 ◽  
Author(s):  
CB Miller ◽  
BA Zehnbauer ◽  
S Piantadosi ◽  
SD Rowley ◽  
RJ Jones
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Therapeutic Results ◽  
Autologous Bone ◽  
Minimal Residual

Despite initial complete remission rates exceeding 70%, the majority of patients with acute myeloid leukemia (AML) and adults with acute lymphocytic leukemia (ALL) eventually relapse. Improving the therapeutic results in acute leukemia requires detecting, and understanding the biology of, the minimal residual leukemia remaining after therapy and responsible for relapse. To investigate the biologic relevance of an in vitro assay for clonogenic leukemia (leukemia colony- forming units [CFU-L]) as a measure of minimal residual leukemia, we studied 58 consecutive patients with acute leukemia in complete remission undergoing autologous bone marrow transplantation (BMT) with cyclophosphamide-based therapy. CFU-L were cultured from the pretransplant remission marrows in 45 of 58 patients: 35 of 43 patients with AML and 10 of 15 with ALL. Clonal rearrangements, identical to the patients' overt leukemia when available, were detected in the occult CFU-L from four of the eight patients with ALL in whom adequate DNA for analysis could be obtained from the CFU-L. None of the uncultured pretransplant remission marrows from the 15 ALL patients showed clonal gene rearrangements. We also determined the in vitro sensitivity of the occult CFU-L to 4-hydroperoxycyclophosphamide (4HC), and correlated these results with the outcome of the patients. The sensitivity of the occult CFU-L to 4HC was the only factor that predicted relapse following BMT. The actuarial probability of relapse was 18% in the 23 patients whose CFU-L were sensitive to 4HC compared with 77% in the 22 patients whose CFU-L were resistant (P less than .001). The only factor that influenced the CFU-L sensitivity to 4HC was the type of leukemia. The CFU-L from the AML patients were more sensitive to 4HC than the CFU- L from the ALL patients (P = .001). Occult CFU-L genetically and functionally represent occult leukemia. Therefore, the CFU-L assay should provide a means for studying the biology of minimal residual leukemia and improving the therapeutic results in patients with acute leukemia.

scholarly journals Autologous bone marrow transplantation in acute leukemia: a phase I study of in vitro treatment of marrow with 4- hydroperoxycyclophosphamide to purge tumor cells

Blood ◽  
1985 ◽  
Vol 65 (6) ◽  
pp. 1504-1510 ◽  
Author(s):  
H Kaizer ◽  
RK Stuart ◽  
R Brookmeyer ◽  
WE Beschorner ◽  
HG Braine ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Acute Leukemia ◽  
Phase I Study ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Autologous Bone ◽  
In Vitro Treatment ◽  
Safe Concentration

Abstract This phase I study was conducted to determine the maximal safe concentration of 4-hydroperoxycyclophosphamide (4HC) that could be used for in vitro treatment of bone marrow from patients with acute leukemia undergoing autologous bone marrow transplantation. Concentrations of 40 to 120 micrograms/mL of 4HC were used in 30 patients with relapsed or high-risk acute leukemia and in six patients with nonleukemic malignancies. All patients received marrow-lethal cytoreductive therapy followed by infusion of the 4HC-treated marrow. Complete inhibition of granulocyte and macrophage colony-forming cells was obtained at 80 micrograms/mL. Nevertheless, only one transplant-related death and otherwise full hematologic recovery was observed at concentrations of 4HC up to 100 micrograms/mL. At 120 micrograms/mL, there were three transplant-related deaths, including two of the three patients who required the infusion of reserve marrow. Among the acute leukemia patients, three remain in complete remission at 1,337, 1,017, and 967 days after transplant. Among the nonleukemic patients, two remain in complete remission at 1,081 and 1,017 days after transplant. At the maximum safe concentration of 4HC (100 micrograms/mL), satisfactory hematologic recovery can be obtained, despite elimination of detectable hematopoietic progenitors.

Autologous Bone Marrow Purging with Lak Cells

1993 ◽  
Vol 16 (5_suppl) ◽  
pp. 108-110 ◽  
Author(s):  
L. Giuliodori ◽  
L. Moretti ◽  
S. Stramigioli ◽  
F. Luchetti ◽  
G.M. Annibali ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Lak Cells ◽  
Marrow Purging ◽  
Autologous Bone ◽  
A Minor ◽  
Bone Marrow Purging

In this study we will demonstrate that LAK cells, in vitro, can lyse hematologic neoplastic cells with a minor toxicity of the staminal autologous marrow cells. In fact, after bone marrow and LAK co-culture at a ratio of 1/1 for 8 hours, the inhibition on the GEMM colonies resulted to be 20% less compared to the untreated marrow. These data make LAK an inviting agent for marrow purging in autologous bone marrow transplantation.

Radiotherapy after High-Dose Chemotherapy Followed by Autologous Bone Marrow Transplantation in Patients with Intermediate or High-Grade Non-Hodgkin's Lymphoma

1996 ◽  
Vol 82 (4) ◽  
pp. 335-338
Author(s):  
Salvina Barra ◽  
Almalina Bacigalupo ◽  
Renzo Corvò ◽  
Marina Guenzi ◽  
Tindaro Scolaro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Complete Remission ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
High Grade ◽  
Bulky Disease ◽  
Autologous Bone

Patients with intermediate or high-grade non-Hodgkin's lymphoma are rarely cured of their disease after the failure of conventional therapy. Autologous bone marrow transplantation (ABMT) offers such patients a new possibility of cure. Our purpose was to evaluate the usefulness of radiotherapy in these patients who did not achieve complete remission of disease after high-dose chemotherapy (HDCT) followed by ABMT or who had previous bulky disease. In this study we examined 10 patients: after HDCT+ABMT, 9 patients had persistent disease and 1 patient with previous bulky disease was in complete remission. All patients underwent involved-field radiotherapy administered by a 6-18 MV linear accelerator, total mean dose 4000 cGy (range, 3200-5000 cGy). At the end of radiotherapy we observed 6 complete responses and 4 progressions of disease outside the radiotherapy field. No serious side effects were observed. To date, of the 6 complete responses 2 have relapsed (after 9 and 11 months) and 4 are alive and disease free at 24 months (range, 8-39 months) after radiotherapy. In our opinion, radiotherapy is an effective treatment after HDCT+ABMT and may have a role in a prospective multidisciplinary approach.

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