melphalan and ranimustine

A 68-year-old man was diagnosed as having bronchial asthma in November 1996. He presented with leukocytosis in June 2002. The WBC count was 29,900/microliter with 82% mature neutrophils showing toxic granules. The neutrophil alkaline phosphatase score and serum level of vitamin B12 were elevated. Bone marrow demonstrated myeloid hyperplasia and plasmacytosis. Cytogenetic and molecular analyses were negative for Philadelphia chromosome and BCR/ABL fusion gene. Lambda-type Bence-Jones protein was detected on the serum and urinary immunoelectrophoresis. The coexistence of chronic neutrophilic leukemia and myeloma was suspected based on the clinical features. The serum level of granulocyte-colony stimulating factor (G-CSF) was elevated. Immunohistochemically, atypical plasma cells were positive for anti G-CSF antibody. Finally, we diagnosed this patient as having a G-CSF-producing myeloma. Treatment with melphalan and prednisolone was initiated without beneficial response. He was then admitted to our hospital for ROAD therapy (ranimustine, vincristine, melphalan, and dexamethasone). The neutrophil count decreased in parallel with the serum G-CSF level. These observations indicated that the neutrophilia in this case was probably caused by a reactive response to G-CSF secreted from the myeloma cells.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Diagnosis, Differential; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Neutrophilic, Chronic; Leukocytosis; Male; Melphalan; Multiple Myeloma; Neutrophils; Nitrosourea Compounds; Treatment Outcome; Vincristine

The outcome of relapsed/refractory HIV-associated lymphoma remains poor, even in the era of combined antiretroviral therapy. However, recent reports showed the efficacy of autologous stem cell transplantation (ASCT). We conducted a single-arm, multicenter phase II study in patients with relapsed/refractory HIV-associated lymphoma to assess the safety and efficacy of ASCT. The study included 14 patients with relapsed/refractory HIV-associated lymphoma. Five patients who achieved partial remission or better after the standard salvage regimen proceeded to ASCT. Conditioning treatment involved ranimustine (300 mg/m2) on day - 6, etoposide (200 mg/m2) on days - 5 to - 3, cytarabine (200 mg/m2) on days - 5 to - 3, and L-PAM (140 mg/m2) on day - 2. All patients achieved engraftment and were alive on day 100 of ASCT. One-year and 2-year overall survival rates were both 40% and 1-year and 2-year progression-free survival rates were both 40%. Grade 2 or 3 diarrhea and oral mucositis were observed in 43% of patients. Cytomegalovirus antigenemia, retinitis, and bacterial infections were noted in 43%, 29%, and 29% of patients, respectively. Therapy-related death was not observed. Although the number of enrolled patients was insufficient for statistical analysis. ASCT was feasible and safe for relapsed/refractory HIV-associated lymphoma.Registration: This study is registered in UMIN-CTR (UMIN000003159).

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Etoposide; Feasibility Studies; Humans; Lymphoma, AIDS-Related; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Nitrosourea Compounds; Peripheral Blood Stem Cell Transplantation; Safety; Survival Rate; Transplantation, Autologous

To investigate whether combination chemotherapy with vincristine, cyclophosphamide, prednisolone, and melphalan (COP/ MP) with the addition of ranimustine (MCNU) (MCNU-COP/MP) is superior to the slightly modified COP/MP (mCOP/MP) regimen in multiple myeloma (MM), a multicenter randomized study was performed. Two hundred ten patients with newly diagnosed, overt MM not treated with chemotherapy were enrolled from 32 institutions of the Lymphoma Study Group of the Japan Clinical Oncology Group and were randomized to receive either MCNU-COP/MP or mCOP/MP. The response rate (RR) to mCOP/MP was 43.7% (95% confidence interval [CI], 33.9%-53.8%] and to MCNU-COP/MP was 56.1% (95% CI, 46.1%-65.7%) (P = .097). The progression-free survival (PFS) was significantly longer for patients treated with MCNU-COP/MP than for patients treated with mCOP/MP (median, 23.0 months [95% CI, 18.9-25.8] versus 15.8 months [95% CI, 14.1-19.4]) (P = .014). However, no significant difference in overall survival rate (OS) was observed between the groups (median, 49.9 months [95% CI, 40.4-59.1] versus 44.0 months [95%, CI, 32.8-59.8]) (P = .75). Grades 3 and 4 hematological toxicities were more frequently observed with MCNU-COP/MP than with mCOP/MP, but the incidence of grades 3 and 4 nonhematological toxicities was low in both groups. In conclusion, MCNU-COP/MP in comparison with mCOP/MP improved RR and PFS in overt MM; however, this outcome did not contribute to prolonging OS, indicating that addition of MCNU to mCOP/MP has no benefit on survival.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disease-Free Survival; Female; Humans; Japan; Male; Melphalan; Middle Aged; Multiple Myeloma; Nitrosourea Compounds; Prednisone; Treatment Outcome; Vincristine

This pilot study evaluated the efficacy of a new combination chemotherapy with a newly developed nitrosourea derivative ranimustine and evaluated the efficacy of interferon alpha (IFN-alpha) maintenance in previously untreated patients with multiple myeloma (MM). The induction therapy (ROAD-IN) was a 6-week regimen consisting of chemotherapy with ranimustine, vincristine (Oncovin), melphalan (Alkeran) and dexamethasone starting on day 1 and IFN-alpha, which was administered three times weekly for 3 weeks starting on day 22. This was repeated for three cycles. The responders were subsequently randomized into two groups that received or did not receive IFN-alpha as maintenance therapy. Of the 164 patients registered, 161 were evaluated. An objective response to induction therapy was seen in 75% of patients; complete remission (CR) in 38 (24%) and partial remission (PR) in 82 (51%). The median survival for all patients was 3.6 years from registration. The survival of responders (CR + PR) was significantly better than that of non-responders (median survival 4.3 years vs. 1.4 years; 7-year survival rate 32% vs. 9%; P < 0.0001). The IFN-alpha maintenance did not show any advantage for either response duration or survival. This pilot study demonstrated that a comparatively short period of induction therapy with the ROAD-IN regimen produced a rather high response rate and a similar survival rate to those achieved with other longer induction regimens, and that good responders to the initial therapy survived significantly longer than non-responders.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chi-Square Distribution; Connectin; Dexamethasone; Humans; Interferon-alpha; Logistic Models; Melphalan; Multiple Myeloma; Muscle Proteins; Myeloma Proteins; Nitrosourea Compounds; Pilot Projects; Prospective Studies; Remission Induction; Vincristine

To compare VMCP, a multidrug combination chemotherapy comprising vincristine (VCR), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL), with MMPP comprising MPH, ranimustine (MCNU), procarbazine, and PSL as induction, to elucidate the value of alternating combination chemotherapy, and to search for an appropriate maintenance therapy in multiple myeloma.. At 16 institutions in the Nagoya City area, we carried out a randomized trial of VMCP versus MMPP as the initial treatment. Patients who were refractory or resistant to the initial therapy were crossed over into the other arm (crossover trial). For patients who achieved a partial response (PR) or a minor response (MR) and in whom the paraprotein level ceased to decrease, the maintenance therapy was randomized either to an MPH/PSL combination (MP) or to alternating combination therapy (AT) with VMCP and MMPP.. In the 94 evaluable patients of the 111 enrolled, the response rate (PR rate) was 27.7% (13/47) in the VMCP arm and 44.7% (21/47) in the MMPP arm (P = 0.0859). The crossover trial resulted in a PR rate of 15.8% (3/19) for the VMCP-->MMPP crossover and 14.3% (2/14) for the MMPP-->VMCP crossover. The median survival time was 23.4 months for those initially begun in the VMCP arm and 24.9 months for those in the MMPP arm, showing a tendency for better survival during a follow-up of 2-6 years with MMPP treatment, but without statistical significance. The survival time of patients with progressive disease was significantly shorter than that of patients with PR, MR or no change (NC). However, there was no significant difference in the survival rate among those who achieved PR, MR, or NC. As to the maintenance therapy, there was no significant difference in survival between MP therapy and AT. Patients who reached a plateau phase survived significantly longer than those who did not. Except for six cases of grade 3 or 4 neurotoxicity in the VMCP arm, there was no significant difference in the hematologic or gastrointestinal toxicity between the two arms.. We conclude that VMCP is less effective for myeloma than MMPP as the induction treatment, that alternating noncrossresistant chemotherapeutic combinations do not offer an advantage in multiple myeloma, and that patients who reach a plateau phase have a significantly longer survival time.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Humans; Melphalan; Middle Aged; Multiple Myeloma; Nitrosourea Compounds; Prednisolone; Prednisone; Procarbazine; Vincristine

In two consecutive studies of a pilot study and a multicenter trial 16 patients and 61 patients, respectively, with multiple myeloma were treated with the combination chemotherapy (CMVM regimen; the same intermittent high dose dexamethasone as in VAD regimen, MCNU bolus injection of 1.2mg/m2 on day 1, melphalan 12mg/day on days 1-6) plus IFN alpha (HLBI 300MU every day or two) to assess the efficacy and the toxicity of this protocol. Both studies were achieved in the same regimen except for initial 12 days administration of IFN alpha in the multicenter trial. The treatment was repeated 3 times every 6-8 weeks. Complete remission (CR) in which serum and urine M protein disappeared and myeloma cells in bone marrow were eradicated was obtained in 6 in 16 patients (37.5%) in the pilot study and 16 in 61 patients (26.2%) in the multicenter trial. CR plus PR was 68.8% and 68.9% in two studies. The achievement of CR in such high proportion of patients may exhibit a significant advance in the myeloma therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Drug Administration Schedule; Humans; Interferon-alpha; Melphalan; Middle Aged; Multiple Myeloma; Nitrosourea Compounds; Pilot Projects; Remission Induction; Survival Rate; Vincristine

The BEAM regimen consisting of carmustine (BCNU), etoposide, cytarabine, and melphalan (MEL) is widely used before autologous hematopoietic stem cell transplantation (auto-HSCT) for lymphoma. However, intravenous BCNU is not available in Japan, and therefore, ranimustine (MCNU) has been used instead of BCNU (the MEAM regimen). We retrospectively analyzed the outcome of 79 adult patients who underwent auto-HSCT for lymphoma using this regimen in two centers, with 1- and 2-day dosing of MEL, respectively. Three-year overall survival (OS) and progression-free survival (PFS) probabilities were 77.3 and 56.5 % in the entire population and 71.7 and 58.0 % in patients with diffuse large B cell lymphoma. These outcomes were at least equivalent to those with the BEAM regimen. There was no regimen-related pulmonary toxicity. In a multivariate analysis, older age was the only factor that was significantly associated with for OS. In a comparison of the two MEL dosing schedules, while there was no significant differences in either OS or PFS, diarrhea was observed more frequently with 1-day dosing of MEL. In conclusion, the MEAM regimen appeared to be a promising conditioning regimen in auto-HSCT for lymphoma. A large prospective study is warranted to confirm the current findings.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Disease-Free Survival; Dose-Response Relationship, Drug; Etoposide; Febrile Neutropenia; Female; Humans; Lymphoma; Male; Melphalan; Middle Aged; Nausea; Nitrosourea Compounds; Peripheral Blood Stem Cell Transplantation; Retrospective Studies; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult

The number of elderly patients with diffuse large B cell lymphoma (DLBCL) continues to increase but the data regarding autologous stem cell transplantation (ASCT) for elderly patients are limited. We analyzed 484 patients, ages 60 years or over, diagnosed with relapsed/refractory DLBCL who received ASCT from 1993 to 2010 in the Japan Society for Hematopoietic Cell Transplantation database. Median age was 64 years (range, 60 to 78). To evaluate the impact of age at ASCT, patients were classified into 3 groups: those between the ages of 60 to 64, 65 to 69, and 70 years or over. Overall nonrelapse mortality (NRM) at day 100, 1 year, and 2 years was 4.1%, 5.9% and 7.7%, respectively. NRM did not significantly differ among age groups (P = .60). Two-year progression-free survival (PFS) and overall survival (OS) were 48% and 58%, respectively. PFS and OS were significantly longer in patients 60 to 64 years old; however, the survival rate was acceptable even in those 70 or over, with a 2-year OS of 46%. ASCT is feasible in selected elderly patients and age alone should not be a contraindication for ASCT. Eligibility should be individualized and identification of a subset of elderly patients at high risk of treatment-related morbidity or mortality warrants investigation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cyclophosphamide; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Middle Aged; Nitrosourea Compounds; Recurrence; Retrospective Studies; Survival Analysis; Transplantation, Autologous

Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carboplatin; Cisplatin; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Epstein-Barr Virus Infections; Etoposide; Female; Humans; Immunosuppressive Agents; Lymphoma, T-Cell, Peripheral; Melphalan; Methotrexate; Middle Aged; Nitrosourea Compounds; Pharyngitis; Prednisolone; Recurrence; Rituximab; Salvage Therapy; Tacrolimus; Transplantation Conditioning; Transplantation, Homologous; Vincristine; Whole-Body Irradiation

The presence of renal failure in patients with multiple myeloma (MM) has been considered an ominous prognostic factor associated with a significantly decreased life expectancy. The prognostic factors have seldom been analyzed to predict discontinuation of hemodialysis (HD) therapy in MM patients with renal failure after HD initiation. It is clinically very important to predict whether HD can be discontinued after introducing HD in such patients.. All medical and HD records were reviewed in MM patients who underwent HD in the National Center for Global Health and Medicine Hospital between January 1995 and May 2009. Thirty-two patients with MM had undergone HD. The clinical features and the factors that might be associated with recovery of renal function leading to discontinuation of HD in MM patients with severe renal failure were examined.. The factors associated with recovery of renal function and discontinuation of HD were: low International Staging System (ISS) score (p = 0.0034); high response to chemotherapy (p = 0.036); low serum Ca (p = 0.006); low Cr (p = 0.019), and low serum β₂-microglobulin (sβ₂M) (p = 0.002). On multivariate analysis, low serum Ca and sβ₂M were significantly associated with HD discontinuation. Moreover, discontinuing HD was the significant factor associated with improved overall survival in MM patients who required HD at least once.. sβ₂M and Ca were the laboratory parameters that were significant, independent prognostic factors for predicting the probability of recovery from severe renal failure and discontinuation of HD in MM patients who needed HD at least once.

Topics: Acute Kidney Injury; Aged; Antineoplastic Combined Chemotherapy Protocols; beta 2-Microglobulin; Biomarkers; Calcium; Creatinine; Dexamethasone; Doxorubicin; Female; Humans; Kidney; Male; Melphalan; Middle Aged; Multiple Myeloma; Multivariate Analysis; Nitrosourea Compounds; Prednisolone; Prognosis; Recovery of Function; Renal Dialysis; Survival Analysis; Treatment Outcome; Vincristine

AIDS-related lymphoma (ARL) is a serious complication of HIV infection. We performed MEAM (MCNU + etoposide + cytarabine + L-PAM) regimen with autologous stem cell transplantation (ASCT) for three patients with refractory or relapsed ARL. All three patients had been treated with highly active anti-retroviral therapy (HAART) during the course of the treatment regimen and ASCT. The regimen was well tolerable, and no uncontrollable infection was noted. All patients are still alive and maintain complete remission at 24, 20 and 9 months after transplantation. ASCT using MEAM regimen as a conditioning regimen was feasible for our patients with refractory or relapsed ARL.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; HIV Infections; Humans; Lymphoma, AIDS-Related; Male; Melphalan; Nitrosourea Compounds; Recurrence; Salvage Therapy; Transplantation Conditioning; Transplantation, Autologous

We have experienced 4 cases of therapy-related leukemia (TRL) in 119 patients with multiple myeloma (MM) who had received combination chemotherapy including alkylating agents between 1988 and 1998. All 4 cases were acute myelogenous leukemia, 3 were males and 1 was female. Median age at diagnosis of MM was 60 years, and median time to TRL from diagnosis of MM was 5.5 years. The chromosome abnormalities were found in 3 of those cases. All 4 cases were resistant to antileukemic chemotherapy, and median survival time from TRL was only 5.5 months. The TRL in MM is thought to be a more important problem, because recently the treatment for this disease has become more intensive, including high-dose chemotherapy supported by autologous stem cell transplantation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chromosome Aberrations; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Humans; Leukemia, Myeloid, Acute; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasms, Second Primary; Nitrosourea Compounds; Prednisolone; Prednisone; Vincristine

Systemic light-chain deposition due to plasma cell dyscrasias manifests as a form of restrictive cardiomyopathy with diastolic ventricular dysfunction. Although these manifestations are likely to be cardiac amyloidosis, whether these pathological conditions are reversible after treatment of the underlying plasma cell disorders is unknown. To our knowledge, we describe the first patient with cardiac light-chain deposition due to multiple myeloma in whom echocardiographic and biochemical factors of cardiac function were ameliorated dramatically after remission of this disorder. We emphasize that restrictive cardiomyopathy due to light-chain deposition may be reversible and have a relatively better prognosis after remission of plasma cell dyscrasias.

Topics: Adult; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Marrow Examination; Cardiomyopathy, Restrictive; Dyspnea; Echocardiography; Electrocardiography; Hemodynamics; Humans; Immunoglobulin Light Chains; Male; Melphalan; Multiple Myeloma; Nitrosourea Compounds; Prognosis; Remission Induction; Treatment Outcome; Vincristine

A newly designed combination chemotherapy for multiple myeloma, MMCP [ranimustine (MCNU), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL)], was analyzed and compared with the results of our previous randomized trial of VMCP [vincristine, MPH, CPM and PSL] and MMPP [MCNU, MPH, procarbazine and PSL].. MCNU (33.3 mg/m2, div) on day 1 and MPH (4 mg/m2, po), CPM (66.7 mg/m2, po) and PSL (30 mg/m2, po) from day 1 to 4, were administered. Each cycle was repeated every 3 weeks.. From January 1991 until August 1995, 104 patients with multiple myeloma diagnosed at 10 hospitals of Nagoya Cooperative Study Group were enrolled.. Of the 87 evaluable patients, partial response rate for MMCP was 65.5% and was significantly higher than that of VMCP (13/47=27.7%, p<0.0001) and that of MMPP (21/47=44.7%, p=0.0196). A plateau attainment was observed in 49.4%. The percentage of the patients who attained plateau was significantly increased in the MMCP arm than in the VMCP arm (19.1 %, p=0.0017) but was not in comparison with that of MMPP arm (42.6%, p=0.6790). Patients treated with MMCP survived significantly longer than those treated with VMCP or MMPP (p=0.0009 by generalized Wilcoxon test, p=0.0023 by log-rank test) with median survival for MMCP being 31.6 months, for VMCP 22.5 months, and for MMPP 22.9 months. No significant differences were observed with respect to adverse effects among the three regimens.. The newly designed MMCP is a candidate as an induction chemotherapy for multiple myeloma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Nitrosourea Compounds; Prednisolone; Prednisone; Procarbazine; Remission Induction; Survival Rate; Treatment Outcome; Vincristine

IgD myeloma is an infrequent type of multiple myeloma and is characterized by an aggressive clinical behavior and a short survival time. No satisfactory treatments have thus far been established. Recently we treated a patient with IgD(lambda)-type myeloma with glucocorticoids, and succeeded in achieving a complete remission. This case seems to indicate a usefulness of glucocorticoid monotherapy for treating IgD myeloma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Glucocorticoids; Humans; Immunoglobulin D; Immunoglobulin lambda-Chains; Interferons; Melphalan; Methylprednisolone; Middle Aged; Multiple Myeloma; Myeloma Proteins; Nitrosourea Compounds; Prednisolone; Remission Induction; Vincristine

A 52-year-old woman complained of lower back pain and gluteal pain in April 1997, and was found to have anemia, hypercalcemia and renal disorder. In September of the same year, she was diagnosed as having IgA-lambda myeloma (stage IIIA). VMMD-IFN therapy was started in November, 1997, and this resulted in improvement of the M-protein level, and relief of the pain in the lower back and gluteal region. A second course of VMMD-IFN therapy was also effective. In April 1998, however, the back pain worsened, and in July the patient suffered a fall and fractured her left femur. Upon readmission to our hospital, the level of M-protein was lower, and high fever, hypercalcemia, renal disorder, elevation of the LDH level, anemia and thrombocytopenia were observed. Bone marrow examination revealed 30% atypical large-sized CD19-, CD38+, CD56+ myeloma cells and chromosomal abnormalities. Although the symptoms were improved temporarily after a third course of VMMD therapy, disease aggravation occurred again, and extramedullary masses appeared on the head, face and pelvis. VAD therapy was performed without effect, and the patient died about 2 months after recurrence. This was a comparatively rare case of fulminant multiple myeloma occurring in the terminal stage.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cell Transformation, Neoplastic; Dexamethasone; Female; Humans; Immunoglobulin A; Immunoglobulin lambda-Chains; Interferon-alpha; Melphalan; Middle Aged; Multiple Myeloma; Nitrosourea Compounds; Vincristine

There are only 3.3% of patients with multiple myeloma in Japan Myeloma Study Group who have lived longer than ten years. Features associated with long survival include responded well to simple treatment such as melphalan or cyclophosphamide and prednisone, short duration of treated time with long activity and prolonged unmaintained remissions. High-dose melphalan therapy, VAD chemotherapy and MCNU-VP16-melphalan combination were tried for patients relapsed with alkylating agents and the result were reported. Bone marrow transplantation and cytokine therapy for myeloma will be discussed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Administration Schedule; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Nitrosourea Compounds; Podophyllotoxin; Prednisone; Remission Induction; Survival Rate; Vincristine

Untreated twenty patients of multiple myeloma were treated with the chemotherapy protocol as follows: Initial induction therapy;MP continuous or MP intermittent----IFN alpha----steroid pulse. Maintenance therapy;alkylating agents which have no cross resistance were used ((V) MP----(MP)----(V) EP----MCNU). Remission rate (CR+PR) after the initial MP therapy was 45%, and that after including IFN alpha and steroid pulse therapy was 50%, Fifty percent survival rate was almost as same as those reported previously (34M). Our protocol presented here was based on the idea that, initially, myeloma cells with proliferative activity could be affected by MP therapy, and subsequent IFN alpha therapy would have effect even on the residual myeloma cells. Serial checks of 3H-TdR uptake of myeloma cells during the therapy supported this idea. During the maintenance therapy, clinical responses to the initial induction therapy were not aggravated in the responded cases when evaluated by the variation of serum M-protein level. We propose that considering from a point of proliferative activity of myeloma cells is important for designing therapeutic protocols for multiple myeloma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Interferon-alpha; Male; Melphalan; Middle Aged; Multiple Myeloma; Nitrosourea Compounds; Prednisolone; Remission Induction; Vincristine

Seventy patients with progressive multiple myeloma received combination chemotherapy with cyclophosphamide and prednisolone (CP), BCNU, cyclophosphamide, procarbazine and prednisolone (BCPP), and MCNU, cyclophosphamide, melphalan and prednisolone (MCMP) as first line treatment. Total remission rate in patients treated with CP, BCPP, and MCMP was 76.2%, 86.1%, and 91%, and complete response rate 26.1%, 33.3% and 63.7%, respectively, 5-yr survival in the patients treated with CP and BCPP regimen was 51.9 +/- 11.1%, 39.7 +/- 8.9%, respectively, however, the difference was not significant, 1-yr survival in the patients treated with MCMP was 91 +/- 8.7%. It was postulated that long-term survival or cure can only be anticipated if the treatments giving high CR rates was developed. The study, though preliminary, supports the notion that MCMP therapy should be used as primary standard treatment for patients with multiple myeloma.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Drug Evaluation; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Nitrosourea Compounds; Prednisolone; Procarbazine; Remission Induction; Survival Rate

Topics: Antineoplastic Agents; Cell Cycle; Cell Division; Cell Line; Humans; Melphalan; Multiple Myeloma; Nitrosourea Compounds; Tumor Cells, Cultured