melphalan and Leukemia--Lymphoid

Topics: Antineoplastic Agents; Cyclophosphamide; Cytarabine; Dose-Response Relationship, Drug; Etoposide; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Melphalan; Recurrence

Topics: Adrenal Cortex Hormones; Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Breast Neoplasms; Cyclophosphamide; Dacarbazine; Doxorubicin; Drug Therapy, Combination; Dyspnea; Fluorouracil; Hodgkin Disease; Humans; Hypercalcemia; Leukemia; Leukemia, Lymphoid; Lymphoma; Mechlorethamine; Melphalan; Methotrexate; Multiple Myeloma; Palliative Care; Prednisone; Procarbazine; Receptors, Glucocorticoid; Vinblastine; Vincristine; Vomiting

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Drug Evaluation; Drug Resistance; Etoposide; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Melphalan; Neoplasm Recurrence, Local; Neoplasms; Thioguanine; Transplantation, Autologous

There has been a striking improvement in the overall numbers of children and adolescents who become disease-free and remain disease-free as a result of intensive therapy as defined today, for the following cancers: acute nonlymphocytic leukemia (ANLL), non-Hodgkin's lymphoma (NHL), poor risk acute lymphocytic leukemia (ALL), osteosarcoma, and Ewing's sarcoma. The therapy for each of these tumors, with the exception of osteosarcoma, consisted of combination chemotherapy with or without radiotherapy and was started as soon after diagnosis as possible. Aggressive therapy of osteosarcoma has consisted of surgical removal of lung metastases and chemotherapy. Intensive chemotherapy recently has included the use of high doses of certain drugs such as cytosine arabinoside (Ara-C), methotrexate, VP-16-213 and melphalan in the treatment of patients with tumors that are currently difficult to treat.

Topics: Acute Disease; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Etoposide; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Melphalan; Methotrexate; Neoplasms; Osteosarcoma; Risk; Sarcoma, Ewing

This article reviews, for the internist, recent advances in our understanding of the immunology and clinical characteristics of chronic lymphocytic leukemia (CLL). The method of treatment based on clinical staging of CLL and as practiced in the authors' clinic is detailed. It also provides an outline of possible investigation and therapy that may be expected in the coming years.

Topics: Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Carmustine; Chromosomes, Human, 6-12 and X; Cyclophosphamide; Doxorubicin; Female; Humans; Leukemia, Lymphoid; Male; Melphalan; Middle Aged; Neoplasm Staging; Prednisone; T-Lymphocytes; Trisomy; Vincristine

The M-2 protocol (vincristine, cyclophosphamide, BCNU, melphalan, and prednisone) was administered monthly to 63 evaluable patients with advanced chronic lymphocytic leukemia. Complete remission (absence of all clinical and bone marrow evidence of leukemia) and partial response (greater than 50% decrease in organ enlargement and reduction of WBC count to below 15,000 x 10(6)/liter) were achieved in 17% and 44%, respectively, for a total response rate of 61%. The median survivals from therapy of patients achieving a CR, RR, or no response were 73+, 40, and 14 mo respectively. The median survival time from onset of treatment for stages II, III, and IV disease were 47, 20 and 19 mo, respectively, which was not statistically different from historical controls. However, when untreated patients are compared to this latter group, a significant survival advantage from diagnosis was found (p = 0.01), stressing the importance of prior therapy as the only unfavorable prognostic factor. Although complete remissions in CLL, as reflected in apparently normal bone marrow B-lymphocyte markers, can be induced wih acceptable morbidity, the majority of patients relapse after cessation of therapy. An alternative approach to the M-2 protocol will be needed to eradicate the disease.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Drug Therapy, Combination; Female; Femur Head Necrosis; Humans; Hypercalcemia; Leukemia, Lymphoid; Male; Melphalan; Neoplasms, Multiple Primary; Paresthesia; Prednisone; Prognosis; Thrombocytopenia; Vincristine

Topics: Adult; Aged; Arsenic; Benzene; Bone Marrow; Breast Neoplasms; Female; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Male; Melphalan; Middle Aged; Multiple Myeloma; Mycosis Fungoides; Ovarian Neoplasms; Paraproteinemias; Waldenstrom Macroglobulinemia

Topics: Anemia, Aplastic; Benzene; Benzene Derivatives; Bone Marrow; Bone Marrow Cells; Chloramphenicol; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid; Melphalan; Mutation; Occupational Diseases; Oxymetholone; Phenylbutazone

Topics: Adenocarcinoma; Alkylating Agents; Antineoplastic Agents; Breast Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Carmustine; Cyclohexanes; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Hodgkin Disease; Humans; Hydroxyurea; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Melanoma; Melphalan; Multiple Myeloma; Nitrosourea Compounds; Prednisone; 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

Topics: Amyloid; Amyloidosis; Anemia; Antineoplastic Agents; Clinical Trials as Topic; Cyclophosphamide; Hodgkin Disease; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infections; Leukemia, Lymphoid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Prognosis; Pyelonephritis

CBV and BEAM are the two most frequently used regimens for patients with lymphoma undergoing autologous hematopoietic stem-cell transplantation (ASCT). This study compared their morbidity and transplant-related mortality (TRM) in 113 patients with non-Hodgkin's lymphoma (69) and Hodgkin's disease (44) undergoing ASCT between 1990 - 2004. CBV (cyclophosphamide, 6000 mg m(-2); VP-16, 750 mg m(-2); and high-dose BCNU, 800 mg m(-2)) was administered to 75 patients and 38 received BEAM (BCNU, 300 mg m(-2); VP-16, 800 mg m(-2); cytarabine, 800 mg m(-2); melphalan, 140 mg m(-2)). Patients in the BEAM group had a significantly higher median age (p = 0.002) and were more heavily treated before ASCT (p = 0.003). More patients showed active disease at transplant in the BEAM group (p = 0.04). Sinusoidal obstruction syndrome (SOS) was more frequent in the CBV group (11% vs 0%, p = 0.048). There were 20 (18%) transplant-related deaths, 18 in the CBV and two in the BEAM group. Infectious complications (12 patients, seven with pneumonia) and SOS (four) were the most frequent causes of death. The cumulative incidences of TRM were 25% in the CBV and 7% in the BEAM group (p = 0.02). CBV thus produced a higher incidence of SOS and TRM than BEAM in this series.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Infections; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Male; Melphalan; Middle Aged; Morbidity; Mortality; Podophyllotoxin; Transplantation Conditioning; Transplantation, Autologous

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Drug Evaluation; Drug Resistance; Etoposide; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Melphalan; Neoplasm Recurrence, Local; Neoplasms; Thioguanine; Transplantation, Autologous

Topics: Adolescent; Child; Child, Preschool; Clinical Trials as Topic; Drug Evaluation; Humans; Infant; Leukemia, Lymphoid; Melphalan; Neoplasm Staging

Topics: Amyloid; Amyloidosis; Anemia; Antineoplastic Agents; Clinical Trials as Topic; Cyclophosphamide; Hodgkin Disease; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infections; Leukemia, Lymphoid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Prognosis; Pyelonephritis

Topics: Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; CD4 Antigens; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cell Line, Tumor; Clone Cells; Combined Modality Therapy; Culture Media, Conditioned; Cyclophosphamide; Disease Progression; Female; Humans; Leukemia, Lymphoid; Melphalan; Middle Aged; Multiple Myeloma; Neoplastic Stem Cells; Osteolysis; Paraproteinemias; Prednisone; Vincristine

Natural killer (NK)-cell leukemia/lymphoma is a rare entity that has been defined only in recent years. In the Revised European-American Lymphoma and World Health Organization classifications, only the mature NK-cell malignancies are included. However, at least 3 types of precursor NK-cell neoplasms have been reported in the literature. These include myeloid/NK-cell acute leukemia, myeloid/NK-cell precursor acute leukemia, and blastic NK-cell lymphoma/leukemia. These leukemias are characterized by the presence of blasts, which express CD56, in the peripheral blood, bone marrow, lymph nodes, and/or extranodal tissues. We report a case that is morphologically consistent with myeloid/NK-cell acute leukemia but immunologically is myeloid/NK-cell precursor acute leukemia. This case is unique in its cutaneous presentation without involvement of the peripheral blood. Extensive flow cytometric studies were performed on the skin biopsy and bone marrow aspirate specimens, which included many markers that had not been tested before in these entities. The clinical implications of these findings are discussed.

Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carmustine; CD2 Antigens; Cytarabine; Flow Cytometry; Humans; Immunophenotyping; Killer Cells, Natural; Leukemia, Lymphoid; Male; Melphalan; Podophyllotoxin

Twenty-six patients (median age 33 years) with poor-risk malignancies were treated with high-dose combination chemotherapy associating BCNU-etoposide-cytosine arabinoside and melphalan (BEAM) followed by autologous bone marrow transplantation (ABMT). Twenty-one patients had malignant lymphomas, three, acute lymphoblastic leukemia (ALL), and two, malignant thymomas. Eleven patients (group 1) were not in complete remission (CR) at the time of BEAM, and fifteen patients (group 2) were in CR. Hematological recovery occurred in all patients. The duration of aplasia and the non-hematological toxicities were similar in both groups. Ten of the eleven patients (group 1) evaluable for response achieved CR and one achieved partial remission (PR). Five patients relapsed, and five are in continuous CR with a short follow-up (median 8 months). Among the fifteen patients in CR at the time of BEAM (group 2), four patients relapsed and ten patients are in unmaintained continuous CR with a median follow-up of 15 months (one patient died in CR). The disease-free survival is 53%, with 29% for patients receiving BEAM while in relapse (group 1) and 65% for patients receiving BEAM while in CR (group 2). These data indicate that BEAM followed by ABMT can produce a high antitumor response with an acceptable toxicity in patients with poor-risk malignancies.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Child; Child, Preschool; Combined Modality Therapy; Cytarabine; Etoposide; Female; Hematologic Diseases; Humans; Leukemia, Lymphoid; Lymphoma; Male; Melphalan; Middle Aged; Recurrence; Remission Induction; Thymoma; Thymus Neoplasms

We investigated the transport of [chloroethyl-14C]melphalan with lymphocytes from three groups of patients with chronic lymphocytic leukemia (untreated, treated sensitive, and treated resistant). There was no significant difference in the Km or Vmax of melphalan transport in lymphocytes from the three groups. In addition, there were no significant differences in intracellular melphalan levels after a 35-min incubation with 5.4 microM melphalan among the three groups. There was no evidence of intracellular metabolism of melphalan to dihydroxymelphalan except in lymphocytes from one treated sensitive patient. DL-2-Aminobicyclo[2,2,1]heptane-2-carboxylic acid, a specific analogue of the sodium-independent leucine-preferring amino acid transport system, inhibited the uptake of melphalan to a greater extent in lymphocytes from resistant patients than in those of untreated patients. Glutathione levels were not significantly different in lymphocytes from resistant patients as compared to those of untreated patients. The percentage of DNA cross-links as determined by an ethidium bromide fluorescence assay was 2-5-fold greater in lymphocytes from untreated patients than in those of resistant patients. These results suggest that resistance to the nitrogen mustards in patients with chronic lymphocytic leukemia is secondary to neither a transport defect nor alteration in intracellular melphalan levels but rather due to some other mechanism responsible for decreased DNA cross-links.

Topics: Amino Acids; Biological Transport; Cells, Cultured; Cross-Linking Reagents; DNA; DNA Damage; Drug Resistance; Glutathione; In Vitro Techniques; Leukemia, Lymphoid; Lymphocytes; Melphalan

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leukemia, Lymphoid; Lomustine; Male; Melphalan; Middle Aged; Neoplasm Staging; Prednisone

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Cells; Dexamethasone; Humans; Leukemia, Lymphoid; Male; Melphalan

K 18, an IgG-Melphalan conjugate was administered to 30 patients, who had recurrent hematopoietic malignancy. Ten out of the 30 patients received single doses of 1 to 20 enteric tablets containing 10 mg of K 18, as a phase I study. No side effects were observed. K 18 was administered every day to the remaining 20 patients in order to evaluate the side effects and therapeutic effects, as a phase II study. One patient attained partial remission. Although no remission effect was obtained in 14 of the 20 patients, antitumor effects such as a decrease in leukemia cells, were observed in 4 of 20 patients. As to side effects, neither recurrence of tumor nor cumulative toxicity were shown in one patient with NHL who received only K 18 for 14 months as maintenance therapy. Evaluation of antitumor effect was difficult in the case of the remaining 4 patients. In the 20 cases who entered the phase II study, a decrease in neutrophils was observed in 2 patients, a slight decrease in platelets in 3 patients and increased transaminase activity in one patient as side effects of K 18. In brief, compared with Melphalan, K 18 has between 1.3 and 2 times a more potent therapeutic effect, with extremely low side effects.

Topics: Administration, Oral; Adolescent; Adult; Drug Administration Schedule; Drug Evaluation; Female; Humans; Immunoglobulin G; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Melphalan; Middle Aged; Multiple Myeloma

Dose-effect relationships of high-dose melphalan were evaluated in 37 patients with measurable relapsed or refractory acute leukemias. Thirteen patients (Group 1) received 70-100 mg/m2 of melphalan without marrow rescue and 24 patients (Group 2) received 140-180 mg/m2 of melphalan followed by marrow transplantation. Patients in both groups were comparable with respect to age, sex, diagnosis, and status of the leukemia. The complete remission rate was 23% in Group 1 versus 75% in Group 2 (P less than 0.01). Hematological recovery of remission patients was not statistically different in either group. Nonhematological toxicity was comparable in the two dose ranges examined. These results demonstrate the existence of a dose-response effect of high-dose melphalan regimens in relapsed acute leukemias, without marked increases in nonhematological toxicity with these doses.

Topics: Acute Disease; Adolescent; Adult; Aged; Bone Marrow; Bone Marrow Transplantation; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Hematologic Diseases; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Melphalan; Middle Aged; Retrospective Studies

Experience with 19 autologous bone marrow transplantations shows that this approach may produce a high proportion of complete remissions in otherwise resistant tumours. Although most responses are of short duration, they suggest that longterm disease-free survival may be achieved in patients with poor prognosis if treated earlier in the course of disease.

Topics: Adult; Bone Marrow Transplantation; Child; Cyclophosphamide; Female; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Male; Melphalan; Middle Aged; Postoperative Complications; Remission Induction

The M-2 protocol was administered every 5 weeks to 25 patients with stage III and IV chronic lymphocytic leukemia (CLL). Complete remission (CR; absence of all clinical and bone marrow evidence of leukemia including normal immune markers for monoclonal disease) and partial remission (PR; greater than 50% decrease in organ enlargement and reduction of WBC count to below 15,000 X 10(6)/l) were achieved in 20 and 48%, respectively. A median number of 24 cycles of therapy was required to produce a CR. The median duration of unmaintained remission was 12 months. All CR patients are still surviving. The median survival of the PR patients and the overall groups is 21 months. To improve the CR rate and survival in patients with advanced CLL, more effective methods of determining residual leukemic cells and different treatment strategies will be needed.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Humans; Leukemia, Lymphoid; Melphalan; Middle Aged; Neoplasm Staging; Prednisone; Prognosis; Vincristine

The incidence of a lymphoreticular system malignancy in patients with chronic lymphocytic leukemia (CLL), Richter's syndrome (RS), is 3.3 to 10.6%. In 89 cases in the literature, the second neoplasm was either reticulum cell sarcoma or large cell diffuse histiocytic lymphoma (DHL), and there were 61 cases of Hodgkin's disease (HD). In a few cases the lymphoma was simultaneously diagnosed, for other cases an association with preexisting CLL was reported. Appearance of lymphoma was associated with leukemia regression for only 4 patients with DHL and 3 with HD. We report one case of B-lymphocyte CLL with macroglobulinemia, treated with melphalan and prednisone, in which DHL developed and the hematologic and histologic signs of CLL and of paraproteinemia remissed. Such patients might constitute a subgroup or a variant of RS. Since the non-Hodgkin malignant lymphomas (NHML) are considered to be monoclonal neoplastic expansion of the B-cell or T-cell lymphocytes, and since in some cases it has been proved that the proliferative cell clone was the same as that of the initial lymphoproliferative disease, RS could be a dedifferentiation or a transformation of CLL, resulting in an aggressive clinical course. The inclusion in this syndrome of CLL cases associated with HD is still controversial. Many of these cases could be giant cell pleomorphic lymphomas, while, on the contrary, in typical cases this association might be merely fortuitous.

Topics: Blood Transfusion; Female; Hemosiderosis; Humans; Immunoglobulin M; Leukemia, Lymphoid; Lymph Nodes; Lymphatic Diseases; Melphalan; Middle Aged; Paraproteinemias; Prednisone; Syndrome

A patient with multiple myeloma who subsequently developed chronic lymphocytic leukemia is reported. Initial studies demonstrated clinical and hematological features of multiple myeloma with an IgM lambda paraprotein. Skeletal disease was a significant presenting feature, although relapse occurred in extraosseous sites, particularly the pleura. He developed chronic lymphatic leukemia 31 months later and immunological studies showed the malignant lymphocytes to have kappa (Kappa) light chain surface immunoglobulin, demonstrating separate clonal origin of this patient's two B-cell malignancies.

Topics: Aged; Bone Marrow; Bone Neoplasms; Humans; Immunoglobulins; Leukemia, Lymphoid; Lymphocytes; Male; Melphalan; Multiple Myeloma; Ribs

In these studies, we report adaptation of a colony-forming assay to chronic lymphocytic leukemia (CLL) peripheral blood cells. T-lymphocyte-depleted CLL peripheral blood cells were cultured with irradiated, normal T cells and media conditioned by normal, mitogen-stimulated T cells in methylcellulose. Colonies containing small and transformed lymphocytes appeared after 5-7 days incubation. The plating efficiency of CLL colonies was 0.15 +/- 0.08% (x +/- S.D.), similar to that of other colony-forming systems. The majority of CLL colony-forming cells were in S phase (50 +/- 4% x +/- S.E.) as determined by thymidine suicide and the fraction of colony-forming cells in S phase was inversely related to the WBC. Cells harvested from CLL colonies lacked surface markers for T lymphocytes and stained positively for monoclonal surface and/or cytoplasmic immunoglobulin light chains. A 1-h incubation was used to study the in vitro response of CLL colony-forming cells to adriamycin and melphalan. Preliminary studies suggest differences in patterns of in vitro sensitivity to melphalan between patients previously treated with alkylating agents and those who had not received treatment. This system can be used to study regulation of CLL cell proliferation, and may have utility in predicting response to chemotherapeutic agents.

Topics: Cell Division; Cells, Cultured; Colony-Forming Units Assay; Doxorubicin; Erythrocytes; Humans; Leukemia, Lymphoid; Lymphocytes; Melphalan; Mitogens

Topics: Adult; Aged; Antineoplastic Agents; Busulfan; Chlorambucil; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Melphalan; Middle Aged; Multiple Myeloma; Pleural Effusion; Pulmonary Fibrosis

Several new cyclopentenones related to helenalin have been synthesized as potential alkylating antitumor agents. The procedure involved the transformation of 2-methyl-2-carbethoxycyclopentanone (2) to an ethylene ketal 3, bromination of 3 followed by dehydrobromination to yield a ketal olefin 5, reduction of 5 to the alcohol 6, conversion of 6 to the corresponding hydroxycyclopentenone 7, and estrification of 7 to afford the cyclopentenone esters 8--11. Biological assays indicated that only cyclopentenones possessing a conjugated ester side chain, such as 9 and 10, demonstrated significant in vitro cytotoxicity against the growth of tissue culture cells originating from human epidermoid carcinoma of the larynx (H.Ep.-2) as well as in vivo antitumor activity in Walker 256 carcinosarcoma in rats and P-388 lymphocytic leukemia in mice.

Topics: Animals; Antineoplastic Agents, Phytogenic; Carcinoma 256, Walker; Cells, Cultured; Cyclopentanes; Leukemia, Experimental; Leukemia, Lymphoid; Male; Mice; Mice, Inbred DBA; Rats; Sesquiterpenes; Sesquiterpenes, Guaiane

Topics: Asparaginase; Child; Cyclophosphamide; Cytosine; Daunorubicin; Doxorubicin; Drug Therapy, Combination; Hodgkin Disease; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Melphalan; Mercaptopurine; Methotrexate; Neoplasms; Nitrogen Mustard Compounds; Osteosarcoma; Prednisone; Procarbazine; Prognosis; Remission, Spontaneous; Rhabdomyosarcoma; Teniposide; Thioguanine; Vincristine; Wilms Tumor

Acute myelocytic leukemia occurring many years after intensive radiotherapy and/or chemotherapy has been reported in 82 patients with Hodgkin's disease, 58 patients with multiple myeloma, and 40 patients with chronic lymphocytic leukemia. The precise incidence of this occurrence is uncertain, since the total number of patients at risk is unknown. Most patients with Hodgkin's disease had received intensive radiation therapy. Many also received chemotherapy. One-third of the patients with myeloma were treated only with melphalan. Acute leukemia may occur as part of the natural history of Hodgkin's disease and multiple myeloma; it has been seen with increasing frequency in recent years due to improved survival secondary to better treatment. It is also possible that radiotherapy and/or chemotherapy may be causally related to the development of acute leukemia.

Topics: Antineoplastic Agents; Hodgkin Disease; Humans; Leukemia, Lymphoid; Melphalan; Multiple Myeloma; Neoplasms; Radiotherapy

An investigation was undertaken of the mechanism of resistance to nitrogen mustard (HN2) and other alkylating agents, with particular emphasis on the interaction between cross-resistance and drug transport mechanisms in L5178Y lymphoblasts. Dose-survival curves demonstrated that the D0 for HN2-sensitive cells (L5178Y) treated with HN2 in vitro was 9.79 ng/ml and the D0 for HN2-resistant cells (L5178Y/HN2) was 181.11 ng/ml; thus, sensitive cells were 18.5-fold more responsive than were resistant cells and the difference was highly significant (p less than 0.001). A similar evaluation of 5 additional alkylating agents, including chlorambucil, melphalan, 1,3-bis(2-chloroethyl)-l-nitrosourea, Mitomycin C, and 2,3,5-tris(ethyleneimino)-1,4-benzoquinone, revealed that L5178Y/HN2 cells were also cross-resistant, in part, to each of these compounds. Furthermore, the degree of cross-resistance was remarkably similar; for each drug, dose-survival studies showed that HN2-resistant cells were approximately 2- to 3-fold more resistant to therapy than were sensitive cells. L5178Y/HN2 cells were also cross-resistant to cyclophosphamide in vivo; after treatment with cyclophosphamide, DBA/2 female mice that were given inoculations of L5178Y cells, but not those given transplants of L5178Y/HN2 cells, showed a significant prolongation of survival time (p less than 0.01). Transport of HN2, hydrolyzed derivative of HN2 and choline by L5178Y lymphoblasts in vitro was not competitively inhibited by any of the other alkylating agents, suggesting that transport of these compounds was by an independent mechanism. These findings suggest that the mechanism whereby L5178Y/HN2 cells are cross-resistant to other alkylating agents may involve nontransport factors and that these other drugs may bypass a major portion of HN2 resistance by using independent transport systems.

Topics: Alkylating Agents; Animals; Binding, Competitive; Biological Transport; Carmustine; Cell Line; Chlorambucil; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Resistance; Female; Leukemia, Experimental; Leukemia, Lymphoid; Male; Mechlorethamine; Melphalan; Mice; Mice, Inbred DBA; Mitomycins

Topics: Aged; Alkylating Agents; Biopsy; Bone Marrow; Chlorambucil; Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Male; Melphalan; Middle Aged; Multiple Myeloma; Uracil Mustard; Waldenstrom Macroglobulinemia

Topics: Animals; Antineoplastic Agents; Biological Assay; Carmustine; Cyclohexanes; Cyclophosphamide; Cytarabine; Daunorubicin; Disease Models, Animal; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Fluorouracil; Hodgkin Disease; Humans; Leukemia; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Male; Mechlorethamine; Melphalan; Mice; Mice, Inbred AKR; Multiple Myeloma; Nitrosourea Compounds; Prednisone; Remission, Spontaneous; Vinblastine; Vincristine

Topics: Aged; Autopsy; Biopsy; Bone Marrow Cells; Cyclophosphamide; Female; Heart Neoplasms; Humans; Kidney Neoplasms; Leukemia, Lymphoid; Lymphocytes; Male; Melphalan; Middle Aged; Multiple Myeloma; Nasal Polyps; Nose Neoplasms; Osteitis Deformans; Plasmacytoma; Pleural Effusion; Prednisolone; Radiography

Topics: Adrenal Glands; Animals; BCG Vaccine; Corynebacterium; Cyclophosphamide; Disease Models, Animal; Immunotherapy; Kidney; Leukemia, Experimental; Leukemia, Lymphoid; Liver; Lung; Lymph Nodes; Male; Melphalan; Microscopy, Electron; Mycobacterium bovis; Myocardium; Pancreas; Rats; Spleen; Testis; Thymus Gland; Urinary Bladder

Topics: Aged; Animals; Antibodies, Anti-Idiotypic; B-Lymphocytes; Binding Sites, Antibody; Bone Marrow; Bone Marrow Cells; Goats; Humans; Immune Sera; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Iodine Radioisotopes; Leukemia, Lymphoid; Melphalan; Middle Aged; Multiple Myeloma

Topics: Agammaglobulinemia; Antibodies; Antigens, Bacterial; Blood Protein Disorders; Blood Proteins; Busulfan; Chlorambucil; Electrophoresis, Paper; Hodgkin Disease; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin A; Immunoglobulins; Immunosuppression Therapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mannomustine; Melphalan; Primary Myelofibrosis; Radiation Effects; Saliva; Skin Tests; Spleen; Time Factors

Topics: Age Factors; Antibody Formation; Arteritis; Bence Jones Protein; Blood Protein Disorders; Blood Protein Electrophoresis; Clone Cells; Cyclophosphamide; Female; gamma-Globulins; Humans; Hypergammaglobulinemia; Immunochemistry; Leukemia, Lymphoid; Lymphocytes; Macroglobulins; Male; Melphalan; Multiple Myeloma; Plasma Cells; Terminology as Topic; Waldenstrom Macroglobulinemia

Topics: Antineoplastic Agents; Asparaginase; Burkitt Lymphoma; Choriocarcinoma; Cyclophosphamide; Cytarabine; Dactinomycin; Daunorubicin; Female; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Melphalan; Mercaptopurine; Methotrexate; Prednisone; Pregnancy; Vincristine; Wilms Tumor

Topics: Adenocarcinoma; Animals; Fluorides; Injections, Intraperitoneal; Leukemia, Experimental; Leukemia, Lymphoid; Mammary Neoplasms, Experimental; Melphalan; Mice; Phenformin; Sarcoma 37

Topics: Cyclophosphamide; Leukemia; Leukemia, Experimental; Leukemia, Lymphoid; Lymphocytes; Melphalan; Mice; Moloney murine leukemia virus; Oncogenic Viruses; Radiation Effects; Research; Triethylenemelamine

Topics: Blood Protein Disorders; Blood Protein Electrophoresis; Cyclophosphamide; Drug Therapy; gamma-Globulins; Geriatrics; Hospitals, General; Humans; Leukemia; Leukemia, Lymphoid; Lymphocytes; Melphalan; Multiple Myeloma; Myeloma Proteins; Neoplasms; Vascular Diseases; Waldenstrom Macroglobulinemia

Topics: Adolescent; Child; Geriatrics; Head and Neck Neoplasms; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mandibular Neoplasms; Maxillary Neoplasms; Melanoma; Melphalan; Multiple Myeloma; Neoplasms; Orbital Neoplasms; Plasmacytoma; Sarcoma; Sarcoma, Kaposi

Topics: Animals; Antineoplastic Agents; Antiviral Agents; Cyclophosphamide; Fluorouracil; Leukemia; Leukemia, Experimental; Leukemia, Lymphoid; Melphalan; Mercaptopurine; Mice; Oncogenic Viruses; Pathology; Pharmacology; Rauscher Virus; Research; Splenomegaly; Thiosemicarbazones; Vincristine