Limiting-dilution analysis for the determination of leukemic cell frequencies after bone marrow decontamination with mafosfamide or merocyanine 540
To stimulate a leukemia remission marrow, cell suspensions of normal human bone marrow were mixed with human acute lymphoblastic or myelogenous leukemic cells of the CCRF-SF, Nalm-6, and K-562 lines. The cell mixtures were incubated in vitro with mafosfamide (AZ) or with the photoreactive dye merocyanine 540 (MC-540). A quantity of 10(4) cells of the treated suspensions was dispensed into microculture plates, and graded cell numbers of the line used to contaminate the normal marrow were added. Limiting-dilution analysis was used to estimate the frequency of leukemia cells persisting after treatment with the decontaminating agents. Treatment with AZ or MC-540 produced a total elimination (ie, 6 logs or 5.3 logs respectively) of B cell acute leukemia cells (CCRF-SB), whereas nearly 1.7 logs and 2 logs of K-562 acute myelogenous blasts were still present in the cell mixtures after treatment with MC-540 and AZ, respectively. Treatment of the Nalm-6-contaminated cell mixtures with AZ resulted in 100% elimination of clonogenic cells, whereas nearly 80% decontamination was obtained with MC-540. Our results suggest that treatment with AZ could be an effective method of eliminating clonogenic tumor cells from human bone marrow. MC-540, shown by previous studies to spare sufficient pluripotential stem cells to ensure hemopoietic reconstitution in the murine model and in clinical application, has comparable effects and merits trials for possible clinical use in autologous bone marrow transplantation.
- Research Organization:
- Ospedale Civile, Pesaro, Italy
- OSTI ID:
- 5665476
- Journal Information:
- Blood; (United States), Vol. 70:5
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
RADIOSENSITIZERS
TESTING
TUMOR CELLS
SENSITIVITY
BONE MARROW
LEUKEMIA
MAN
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BODY
DISEASES
DRUGS
HEMATOPOIETIC SYSTEM
HEMIC DISEASES
MAMMALS
NEOPLASMS
ORGANS
PRIMATES
TISSUES
VERTEBRATES
560151* - Radiation Effects on Animals- Man
550603 - Medicine- External Radiation in Therapy- (1980-)