mercaptopurine and Multiple-Myeloma

Although cytotoxic immunosuppressive agents play an unquestionably useful role in treating many neoplastic and non-neoplastic disorders, there is accumulating evidence that the toxicity associated with their use is considerable. The therapeutic successes obtained with antitumor agents have led to increases in the life span of cancer patients, but have also provided the opportunity for this toxicity to become manifest. A search of the available literature was carried out, with emphasis on cases in which a malignancy developed in patients following chemotherapy for either neoplastic or non-neoplastic (e.g., renal transplantation, psoriasis) conditions; particular focus was given to the incidence of acute myelogenous leukemia in various groups of Hodgkin's disease and multiple myeloma patients. That patients with nonmalignant conditions treated with cytotoxic immunosuppressive agents are also at increased risk of developing a malignancy raises the possibility that these agents may have oncogenic potential. Therefore, one may be faced with the paradox that the patients benefiting most from chemotherapy may be at highest risk of suffering its consequences.

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Azathioprine; Burkitt Lymphoma; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Female; Hodgkin Disease; Humans; Immunosuppressive Agents; Kidney Neoplasms; Leukemia, Myeloid, Acute; Lymphoma; Mechlorethamine; Melphalan; Mercaptopurine; Methotrexate; Mice; Multiple Myeloma; Neoplasms; Prednisone; Pregnancy; Procarbazine; Time Factors; Vincristine

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Bone Marrow; Bone Marrow Cells; Cell Division; Cyclophosphamide; Cytarabine; Female; Fluorouracil; Humans; Leukemia L1210; Leukemia, Lymphoid; Lymphoma; Melphalan; Mercaptopurine; Methotrexate; Mice; Multiple Myeloma; Neoplasms; Nitrogen Mustard Compounds; Prednisone; Pregnancy; Time Factors; Trophoblastic Neoplasms; Vinblastine

In the present study, we analyzed the cell cycle distribution of bone marrow (BM) cells in 120 untreated multiple myeloma patients using a DNA/CD38 double-staining technique at flow cytometry in which plasma cells (PCs) can be clearly discriminated from residual BM cells based on their CD38 expression. This approach allows us to determine the proliferative activity of both PCs and residual normal BM cells. The percentage of S-phase cells in the myelomatous population was found to be significantly lower than that of the residual normal BM cells (P < .001). Regarding the proliferative activity of myelomatous cells, patients with a high number of S-phase PCs (> 3%) showed a significantly (P < .05) increased incidence of anemia and hypercalcemia; higher values of beta 2-microglobulin (beta 2M), urea, and creatinine; and higher numbers of peripheral blood natural killer cells, as well as a poor prognosis as assessed both by response duration and overall survival. With respect to the residual BM normal fraction, a low proliferative activity was significantly (P < .05) associated with the presence of anemia and neutropenia together with increased numbers of BM PCs, a higher incidence of Bence Jones myelomas, and DNA diploidy. Multivariate analysis showed that the number of S-phase PCs was the most important independent prognostic factor, allowing us to discriminate two subgroups of patients with different prognoses, even within the same clinical stage. Moreover, the S-phase PCs, together with beta 2M, age, and performance status, represent the best combination of disease characteristics for stratifying patients according to prognosis and allow the establishment of a simple and powerful staging system for multiple myeloma patients. In addition, this classification can be used for planning treatment in patients who are candidates for transplantation.

Topics: ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; beta 2-Microglobulin; Bone Marrow; Bone Marrow Examination; Cohort Studies; DNA, Neoplasm; Female; Flow Cytometry; Humans; Life Tables; Male; Membrane Glycoproteins; Mercaptopurine; Methotrexate; Middle Aged; Mitotic Index; Multiple Myeloma; Neoplasm Staging; Plasma Cells; Prednisone; Prognosis; Risk Factors; S Phase; Survival Analysis; Treatment Outcome; Vincristine

The number of circulating hematopoietic progenitor cells was determined during 47 courses of chemotherapy in 23 patients with hematopoietic malignancies. rhG-CSF was given subcutaneously to 14 patients to rescue chemotherapy-induced neutropenia following 22 courses of chemotherapy. The mean numbers of CFU-GM in patients with malignant lymphoma (ML), acute leukemia (AL) and myeloma (MM) were 56.0 +/- 58.8 (mean +/- SD), 46.7 +/- 66.0 and 11.0 +/- 11.1 CFU-GM/ml, respectively. The number of CFU-GM in MM was significantly less than in normal subjects (51.2 +/- 30.6 CFU-GM/ml). The number of CFU-GM in PB in all patients began to rise between 2 days before and 8 days after nadir of WBC count, and then reached the peak at the subsequent 5 days. The peak values of CFU-GM in ML, AL and MM were 711.3 +/- 974.7, 660.0 +/- 374.7 and 403.6 +/- 232.5 CFU-GM/ml, respectively, but there was no statistical difference among them. When ML patients were treated with rhG-CSF, the CFU-GM peak values increased as much as 5.5-folds compared with those following chemotherapy only. However, neither the period from nadir to start of increase in the CFU-GM count nor the time of the CFU-GM peak showed any significant change. These results indicate that the administration of rhG-CSF makes it possible to increase the number of circulating progenitor cells. It appears possible in most of the patients with hematopoietic malignancies to harvest the sufficient number of progenitor cells which are necessary for autologous blood stem cell transplantation.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cell Cycle; Colony-Stimulating Factors; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; Leukemia; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Middle Aged; Multiple Myeloma; Prednisolone; Prednisone; Vincristine

Three cases of secondary leukemia developing after chemotherapy and/or radiotherapy for myeloma, mycosis fungoides, and non-Hodgkin's lymphoma are reported. The first case was a 51-year-old man with IgG-lambda myeloma, treated with melphalan and prednisolone, who developed acute myelomonocytic leukemia 54 months after the diagnosis of myeloma. The second case was a 54-year-old woman with mycosis fungoides treated with radiation, predonine, and cyclophosphamide, who developed acute megakaryoblastic leukemia 298 months after the diagnosis of mycosis fungoides. The third case was a 35-year-old woman with stage IV non-Hodgkin's lymphoma treated with VEMP who developed acute myelogenous leukemia 26 months after the diagnosis of malignant lymphoma. All cases showed pancytopenia and two of three cases had morphologic abnormality in several hemopoietic cell lineages in the leukemic stage. There is a possibility that second malignancies are an increasingly recognized complication in the patients treated with a large amount of chemo-radiotherapy.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Leukemia; Leukemia, Megakaryoblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Lymphoma, Non-Hodgkin; Male; Melphalan; Mercaptopurine; Middle Aged; Multiple Myeloma; Mycosis Fungoides; Pancytopenia; Prednisolone; Vincristine

We have reported two cases of multiple myeloma associated concomitantly with pyroglobulinemia and cryoglobulinemia. One of them showed blood picture of plasma cell leukemia. Plasma cell leukemia with two abnormal serum proteins at the same time, has not been reported yet to our knowledge. In that case, the large amounts of plasma cells were detected in the urine sediment.

Topics: Bone Marrow; Cryoglobulins; Humans; Leukemia, Plasma Cell; Male; Mercaptopurine; Middle Aged; Multiple Myeloma; Paraproteinemias; Paraproteins; Plasma Cells; Prednisone; Pyroglobulins

Topics: Anemia, Sideroblastic; Bone Marrow Examination; Cytarabine; Female; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulins; Iron; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Melphalan; Mercaptopurine; Middle Aged; Multiple Myeloma; Muramidase; Precancerous Conditions; Prednisone; Staining and Labeling; Vincristine

Topics: Cytarabine; Female; Humans; Leukemia, Myeloid, Acute; Male; Melphalan; Mercaptopurine; Middle Aged; Multiple Myeloma

Topics: Antineoplastic Agents; Busulfan; Carcinoma, Squamous Cell; Child; Chlorambucil; Choriocarcinoma; Dactinomycin; Female; Fluorouracil; Gonadal Steroid Hormones; Hodgkin Disease; Humans; Hydrazines; Leukemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Mesenchymoma; Methotrexate; Multiple Myeloma; Nitrogen Mustard Compounds; Ovarian Neoplasms; Pregnancy; Prostatic Neoplasms; Steroids; Testicular Neoplasms; Urethane; Vinblastine; Vincristine; Wilms Tumor

Topics: Antineoplastic Agents; Hematologic Diseases; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Multiple Myeloma; Polycythemia Vera; Prednisone; Vincristine; Waldenstrom Macroglobulinemia

Topics: Blood Cell Count; Cytarabine; DNA; Humans; In Vitro Techniques; Injections, Intravenous; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Mercaptopurine; Multiple Myeloma; Prednisone; RNA; Tritium; Uridine; Vincristine

Topics: Alkylating Agents; Aminopterin; Busulfan; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mechlorethamine; Mercaptopurine; Methotrexate; Multiple Myeloma; Neoplasms; Pathology; Primary Myelofibrosis; Sarcoma; Triethylenemelamine; Tuberculosis; Tuberculosis, Pulmonary; Urethane

Topics: Adolescent; Antineoplastic Agents; Busulfan; Child; Cyclophosphamide; Drug Therapy; Humans; Infant; Leukemia; Leukemia, Myeloid; Melphalan; Mercaptopurine; Multiple Myeloma; Neoplasms; Phosphorus Isotopes; Prednisone

Topics: Adrenal Cortex Hormones; Blood Protein Electrophoresis; Bone Marrow Examination; Cyclophosphamide; gamma-Globulins; Humans; Hypercalcemia; Mechlorethamine; Mercaptopurine; Multiple Myeloma; Prognosis; Radiotherapy; Stilbamidines; Toxicology; Uremia; Urethane

Topics: Antineoplastic Agents; Blood Protein Electrophoresis; Diagnosis, Differential; Geriatrics; Liver Cirrhosis; Mercaptopurine; Multiple Myeloma; Neoplasms, Plasma Cell; Nephrosis; Pathology; Phosphorus Isotopes; Plasmacytoma; Purpura; Urethane; Waldenstrom Macroglobulinemia

Topics: Adenocarcinoma; Alkylating Agents; Animals; Antineoplastic Agents; Bence Jones Protein; Cecum; Cyclophosphamide; gamma-Globulins; Intestinal Neoplasms; Mechlorethamine; Mercaptopurine; Methotrexate; Mice; Multiple Myeloma; Neoplasms; Neoplasms, Experimental; Neoplasms, Plasma Cell; Pathology; Pharmacology; Prednisolone; Radiation Effects; Research

Topics: Biopsy; Bone Marrow Cells; Carcinoma; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Lymphoma; Mercaptopurine; Multiple Myeloma; Myositis; Neoplasms; Polymyositis; Prednisone; Sarcoma

Topics: Adolescent; Alkylating Agents; Antimetabolites; Antineoplastic Agents; Blood Cell Count; Female; Glucocorticoids; Humans; Leukemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Multiple Myeloma; Polycythemia Vera

Topics: Adrenal Cortex Hormones; Aged; Bone Marrow; Busulfan; Chlorambucil; Cyclophosphamide; Hodgkin Disease; Humans; Leukemia; Lymphoid Tissue; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Multiple Myeloma; Neoplasms; Sarcoma