melphalan and Chronic-Disease

Topics: Acute Kidney Injury; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Chronic Disease; Combined Modality Therapy; Dexamethasone; Down-Regulation; Doxorubicin; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin lambda-Chains; Kidney Diseases; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloma Proteins; Pyrazines; Remission Induction; Renal Dialysis; Transplantation, Autologous

Mucocutaneous involvement occurs predominantly in primary systemic amyloidosis as well as in myeloma-associated systemic amyloidosis. It is rarely observed in other types of amyloidoses. Signs of such involvement may aid in the early diagnosis of the disease process. Herein, we describe a 64-year-old white male patient with myeloma-associated systemic amyloidosis in whom the disease presented with unique cutaneous lesions consisting of chronic paronychia and palmodigital erythematous swelling and induration of the hands. Following weekly regimens with prednisone (20 mg/day) and melphalan (2 mg/day) administered every 16 weeks, almost complete resolution of the cutaneous lesions was observed after 1 year of therapy. Also, in response to chemotherapy, modest regression of the myelomatous bone lesions and complete resolution of the underlying gammopathy occurred.

Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Chronic Disease; Drug Therapy, Combination; Erythema; Glucocorticoids; Hand Dermatoses; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Paronychia; Prednisone; Recurrence; Time Factors

Patients received. Thirty patients were enrolled from November 2008 to June 2015. Median age at diagnosis was 5.5 years (2-20). Twenty-one had very high-risk NBL (VHR-NBL), that is, stage 4 NBL at diagnosis or at relapse, with insufficient response (i.e., less than a partial response of metastases and more than three mIBG spots) after induction chemotherapy; nine had progressive metastatic relapse. Median Curie score at inclusion was 6 (1-26). Median number of prior lines of treatment was 3 (1-7). Objective response rate was 13% (95% confidence interval [CI]: 4-31) for the whole population, 19% for VHR-NBL, and 0% for progressive relapses. Immediate tolerance was good, with nonhematologic toxicity limited to grade-2 nausea/vomiting in eight patients. Two-year event-free survival was 17% (95% CI: 6-32). Among the 16 patients with VHR-NBL who had not received prior myeloablative busulfan-melphalan consolidation, 13 had at least stable disease after MIITOP; 11 subsequently received busulfan-melphalan; four of them were alive (median follow-up: 7 years).. MIITOP showed acceptable tolerability in this heavily pretreated population and encouraging survival rates in VHR-NBL when followed by busulfan-melphalan.

Topics: 3-Iodobenzylguanidine; Adolescent; Busulfan; Child; Child, Preschool; Chronic Disease; Humans; Melphalan; Neoplasm Recurrence, Local; Neuroblastoma; Topotecan; Young Adult

Post-transplantation cyclophosphamide (PTCY) therapy has made haploidentical transplantation a global reality in adults, but the literature is largely silent on the feasibility of this approach in children. We conducted a prospective study of 20 patients (median age, 12 years; range, 2-20 years) with advanced acute leukemia to evaluate the feasibility of PTCY-based haploidentical peripheral blood stem cell (PBSC) transplantation in children. The conditioning regimen comprised fludarabine, i.v. busulfan, and melphalan (Flu-Bu-Mel). PTCY on days +3 and +4 was followed by mycophenolate mofetil for 14-21 days and cyclosporine for 60 days. Thirteen patients (65%) had refractory or relapsed myelogenous leukemia, and the remainder had high-risk lymphoblastic leukemia. Prompt engraftment was noted at a median of 14 days, with full donor chimerism by day +28. The cumulative incidence of acute and chronic graft-versus-host disease was 35% and 5%, respectively. Nonrelapse mortality at 1 year was 20%. The incidence of disease progression was 25.7%. The actuarial overall survival at 2 years was 64.3% (95% confidence interval, 53.4%-75.2%). Our data suggest that Flu-Bu-Mel-based conditioning followed by PTCY-based haploidentical PBSC transplantation with reduced duration of immunosuppression is feasible in pediatric patients with advanced leukemia.

Topics: Acute Disease; Adolescent; Adult; Allografts; Busulfan; Child; Child, Preschool; Chronic Disease; Cyclophosphamide; Disease-Free Survival; Female; Graft vs Host Disease; Humans; Leukemia, Myeloid, Acute; Male; Melphalan; Peripheral Blood Stem Cell Transplantation; Survival Rate; Transplantation Conditioning; Vidarabine

We evaluated prognostic factors of melphalan/fludarabine-based dose-reduced allografts in patients with multiple myeloma. From 1998 to 2002, 120 patients with multiple myeloma were treated with melphalan/fludarabine followed by allogeneic stem cell transplantation. The cumulative risk at 1 year for treatment-related mortality (TRM) was 18% (95% confidence interval [CI], 12%-28%). In a multivariate analysis, relapse after prior high-dose chemotherapy was the most significant risk factor for TRM (hazard ratio [HR], 2.80; 95% CI, 1.16-6.74; P =.02), relapse (HR, 4.14; 95% CI, 2.04-8.38; P <.001), event-free survival (HR, 3.11; 95% CI, 1.77-5.46; P <.001), and overall survival (HR, 2.69; 95% CI, 1.35-5.35; P =.005). In addition, relapse was also significantly diminished by chronic graft-versus-host disease (GVHD) in a time-dependent Cox model (HR, 0.37; 95% CI, 0.16-0.87; P =.02). At transplantation, 8% of the patients were in complete remission, whereas 27% had progressive disease. After allografting, 49% achieved complete remission, and 38% achieved partial remission. In a subgroup of patients with chemosensitivity at transplantation and no relapse after prior high-dose chemotherapy who underwent transplantation with peripheral blood stem cells (n = 46), the cumulative risk of TRM at 1 year was only 8% (95% CI, 1%-54%). The 2-year estimated event-free and overall survival was 60% (95% CI, 42%-78%) and 75% (95% CI, 59%-91%), respectively, for related donors (n = 34) and was 81% (95% CI, 59%-100%) and 92% (95% CI, 76%-100%), respectively, for unrelated donors (n = 12).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chronic Disease; Female; Graft Survival; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Prognosis; Recurrence; Remission Induction; Salvage Therapy; Survival Analysis; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome; Vidarabine

A reduced-intensity preparative regimen consisting of melphalan and a purine analog was evaluated for allogeneic transplantation in 86 patients who had a variety of hematologic malignancies and were considered poor candidates for conventional myeloablative therapies because of age or comorbidity. Seventy-eight patients received fludarabine 25 mg/m(2) daily for 5 days in combination with melphalan 180 mg/m(2) (n = 66) or 140 mg/m(2) (n = 12). Eight patients received cladribine 12 mg/m(2) continuous infusion for 5 days with melphalan 180 mg/m(2). The median age was 52 years (range, 22-70 years). Disease status at transplantation was either first remission or first chronic phase in 7 patients, untreated first relapse or subsequent remission in 16 patients, and refractory leukemia or transformed chronic myelogenous leukemia in 63 patients. Nonrelapse mortality rates on day 100 were 37.4% for the fludarabine/melphalan combination and 87.5% for the cladribine/melphalan combination. The median percentage of donor cells at 1 month in 75 patients was 100% (range, 0%-100%). The probability of grade 2-4 and 3-4 acute graft-versus-host disease was 0.49 (95% CI, 0.38-0.60) and 0.29 (95% CI, 0.18-0.41), respectively. Disease-free survival at 1 year was 57% for patients in first remission or chronic phase and 49% for patients with untreated first relapse or in a second or later remission. On multivariate analysis the strongest predictor for disease-free survival was a good or intermediate risk category. In summary, fludarabine/melphalan combinations are feasible in older patients with associated comorbidities, and long-term disease control can be achieved with reduced-intensity conditioning in this population.

Topics: Acute Disease; Adenosine; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chronic Disease; Cladribine; Disease-Free Survival; Female; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Survival Rate; Transplantation Chimera; Transplantation Conditioning; Transplantation, Homologous; Vidarabine

Patients with acute leukemias relapsing within 1 year of an allogeneic BMT have a poor prognosis. We studied the use of melphalan 180 mg/m2 followed by allogeneic peripheral blood stem cells (PBSC) as salvage treatment for patients relapsing after related (n = 7) or matched unrelated transplants (n = 3). Diagnoses were AML (n = 4), ALL (n = 3), biphenotypic acute leukemia (n = 2) and CML in blast crisis (n = 1). Eight patients were beyond first relapse and none were in remission. The median time from previous transplant to relapse was 146 days (range 66-206). The melphalan dose was 90 mg/m2 intravenously on days -4 and -3 with PBSC infusion on day 0. GVHD prophylaxis consisted of cyclosporine and methylprednisolone. The median time to an absolute neutrophil count >0.5 x 10(9)/l and to a platelet count >20 x 10(9)/l was 11 and 13 days, respectively. All engrafting patients (n = 8) had 100% donor cells. Two patients died before day 30, but no other grade 3 or 4 toxicity occurred. Acute GVHD grades II-III occurred in two subjects, and chronic GVHD in four. Seven patients achieved CR, but relapsed at a median of 116 days (range 56-614). Leukemia was the cause of death in eight patients. Median survival was 149 days (range 6-614). This treatment produced responses in the majority of this poor prognosis group. However, durable remissions were not observed, and new treatments to consolidate the responses achieved in this setting are needed. This regimen could be considered for short-term disease control to facilitate donor lymphocyte infusion-based immunotherapy or other measures to prevent disease recurrence.

Topics: Acute Disease; Adult; Antineoplastic Agents, Alkylating; Bone Marrow Transplantation; Child; Chronic Disease; Combined Modality Therapy; Dose-Response Relationship, Drug; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Melphalan; Middle Aged; Pilot Projects; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Transplantation Chimera

High-dose melphalan (HDM) improves progression-free survival in multiple myeloma (MM), yet melphalan is a DNA-damaging alkylating agent; therefore, we assessed its mutational effect on surviving myeloma cells by analyzing paired MM samples collected at diagnosis and relapse in the IFM 2009 study. We performed deep whole-genome sequencing on samples from 68 patients, 43 of whom were treated with RVD (lenalidomide, bortezomib, and dexamethasone) and 25 with RVD + HDM. Although the number of mutations was similar at diagnosis in both groups (7137 vs 7230; P = .67), the HDM group had significantly more mutations at relapse (9242 vs 13 383, P = .005). No change in the frequency of copy number alterations or structural variants was observed. The newly acquired mutations were typically associated with DNA damage and double-stranded breaks and were predominantly on the transcribed strand. A machine learning model, using this unique pattern, predicted patients who would receive HDM with high sensitivity, specificity, and positive prediction value. Clonal evolution analysis showed that all patients treated with HDM had clonal selection, whereas a static progression was observed with RVD. A significantly higher percentage of mutations were subclonal in the HDM cohort. Intriguingly, patients treated with HDM who achieved complete remission (CR) had significantly more mutations at relapse yet had similar survival rates as those treated with RVD who achieved CR. This similarity could have been due to HDM relapse samples having significantly more neoantigens. Overall, our study identifies increased genomic changes associated with HDM and provides rationale to further understand clonal complexity.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Chronic Disease; Dexamethasone; Humans; Lenalidomide; Melphalan; Multiple Myeloma; Neoplasm Recurrence, Local; Transplantation, Autologous

Hematopoietic stem cell allograft is a treatment for patients with severe constitutional or acquired hematopoietic system diseases. This act is always linked to complications requiring multidisciplinary care. Our study describes the post-allograft cutaneous complications.. A prospective study was conducted at the Hematology department of "20 Août Hospital" in Casablanca during a period going from January 2018 to December 2020; including all patients who presented acute or chronic cutaneous complications post-allograft.. Twenty-five patients were included. All patients received induction chemotherapy (Busulfan/Fludarabine or Busulfan/Melphalan). A skin infection was found in 8 patients : four cases of Malassezia folliculitis, one case of perineal zona, one case of genital herpes, one case of varicella and one case of Candida sepsis. The acute graft versus host reaction was found in 3 patients, revealed by an erythematous rash all over the body. The chronic graft versus host reaction was found in five patients on a lichenoid form. Nine patients had a hyperpigmentation of the folds followed by detachment in the same areas, concluding to a Busulfan toxidermy.. Hematopoietic stem cell allograft has many complications. The literature mainly specifies hematological and digestive complications, while skin complications are little described. Our series is special by reporting different types and mechanisms of skin complications that can occur; with a predominance of skin graft-on-host reactions and infections. It also reports an unusual Busulfan toxidermy.

Topics: Acute Disease; Adolescent; Adult; Allografts; Busulfan; Candidiasis; Chickenpox; Child; Chronic Disease; Dermatomycoses; Female; Graft vs Host Disease; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Herpes Genitalis; Humans; Induction Chemotherapy; Malassezia; Male; Melphalan; Middle Aged; Morocco; Prospective Studies; Skin Diseases; Skin Diseases, Infectious; Vidarabine; Young Adult

Oral graft-versus-host disease (GVHD) is a significant complication after allogeneic stem cell transplantation (SCT) and there is no consistent information about its characteristics in patients after reduced-intensity conditioning regimen FLU/MEL (fludarabine 120 mg/m² and melphalan 140 mg/m²).. This was a single-centre prospective observational study of patients after allogeneic SCT with FLU/MEL conditioning performed during the period 1/2005-12/2007. Characteristics of oral GVHD were observed in 71 patients. The observation was discontinued due to death, donor lymphocyte infusion (DLI) or new chemotherapy administration.. In 10/2010, the median duration of the observation of the cohort of the patients was 13 (0.2-69) months, and 42 (35-69) months in the still-ongoing 20/71 (28%) patients. Oral acute GVHD had sporadic 7% incidence, whereas oral chronic GVHD was observed in 33% of patients and persisted with median duration of 188 (11-665) days. Clinical and histopathological features were similar in both acute and chronic oral GVHD and included mucosal lichenoid changes, erythema, ulcerations and pseudomembranes, satellite necrosis, apoptotic bodies and lichenoid interface inflammation.. It is necessary to consider complex clinical symptomatology and pathological correlations when classifying the oral GVHD, because local oral symptoms and histopathological features in both acute and chronic oral GVHD forms can be similar. Even though the oral chronic GVHD was mild in the majority of patients, it can be considered as clinically significant due to its incidence, duration and symptomatology. The FLU/MEL conditioning regimen should not be considered as low-risk protocol in this context.

Topics: Acute Disease; Adult; Aged; Chronic Disease; Female; Graft vs Host Disease; Humans; Male; Melphalan; Middle Aged; Mouth Diseases; Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Young Adult

The impact of human leukocyte antigen (HLA) mismatch after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIT) using unrelated donors (UD) is unclear, and may be modulated by T-cell depletion. We therefore examined outcomes of 157 consecutive patients undergoing RIT after uniform conditioning with fludarabine, melphalan, and alemtuzumab (FMC). Donors were 10/10 HLA-matched (MUDs, n = 107) and 6 to 9/10 HLA-matched (MMUDs, n = 50), with no significant differences in baseline characteristics other than increased cytomegalovirus seropositivity in MMUDs. Rates of durable engraftment were high. Graft failure rates (persistent cytopenias with donor chimerism) were similar (8% vs 3%, P = .21), though rejection (recipient chimerism) was more frequent in MMUDs (8% vs 0%, P < .01). There were no significant differences between donors in the incidences of acute graft-versus-host disease (GVHD; 20% vs 22% grade 2-4, respectively, P = .83), chronic extensive GVHD (3-year cumulative incidence [CI] 23% vs 24%, P = .56), or treatment-related mortality (1-year CI 27% vs 27%, P = .96). Furthermore, there was no difference in 3-year overall survival (OS; 53% vs 49%, P = .44). Mismatch occurred at the antigenic level in 40 cases. The outcome in these cases did not differ significantly from the rest of the cohort. We conclude that RIT using HLA-mismatched grafts is a viable option using FMC conditioning.

Topics: Acute Disease; Adolescent; Adult; Aged; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Agents; Chronic Disease; Disease-Free Survival; Female; Graft Rejection; Graft Survival; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; HLA Antigens; Humans; Incidence; Living Donors; Lymphocyte Depletion; Male; Melphalan; Middle Aged; Myeloablative Agonists; Retrospective Studies; Survival Rate; Time Factors; Transplantation Chimera; Transplantation Conditioning; Transplantation, Homologous; Vidarabine

Topics: Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Chronic Disease; Clinical Trials as Topic; Humans; Lenalidomide; Melphalan; Multiple Myeloma; Randomized Controlled Trials as Topic; Remission Induction; Stem Cell Transplantation; Thalidomide; Transplantation, Autologous; Treatment Outcome

The aim of this study was to assess the relationship between radiation therapy (RT) and treatment-related mortality in patients receiving high-dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT) for recurrent/refractory Hodgkin's disease (HD). Between December 1986 and December 1992, 59 patients previously treated at the Princess Margaret Hospital underwent HDCT (etoposide 60 mg/kg, melphalan 160 mg/m2) and ABMT, performed for refractory (13 patients) or relapsed (46 patients) HD. RT was incorporated in the salvage treatment with the intent to achieve complete control of disease prior to ABMT. RT was given before ABMT in 33 patients, and after ABMT in 4 patients. Treatment-related (TR) mortality was defined as any death occurring within 100 days of ABMT. Autopsies were performed for all patients with TR deaths. With a median follow-up of 4.6 years (range 1.2-7.4 years), the actuarial overall survival was 41% +/- 14% at 5 years. We observed 37 deaths, and 10 of these were TR deaths. Among the 24 patients who received thoracic RT before ABMT, there were 8 TR deaths, 3 of these solely attributable to radiation pneumonitis. The remaining 5 TR deaths all had respiratory failure with complicating sepsis as a major medical problem. The interval from RT to ABMT was shorter for 8 patients dying of TR death (mean 37 days; range 0-103 days), than for the 16 survivors (mean 105 days; range 0-263 days) (P = 0.026). Among 9 patients with ABMT within 50 days of thoracic RT, 6 had TR death. In contrast, among the 35 patients without thoracic RT (26 no RT, 9 non-thoracic RT), there were only 2 TR deaths. The 4 patients treated with mantle RT post-ABMT had no serious pulmonary complications. The use of thoracic RT before HDCT and ABMT was associated with a high post-transplant mortality rate. It was most evident in patients who received thoracic RT within 50 days prior to ABMT, or when the target volume included large volume of lung. We recommend that the use of post-transplant RT be investigated to decrease TR mortality.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Chronic Disease; Combined Modality Therapy; Etoposide; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Melphalan; Middle Aged; Prognosis; Radiotherapy; Recurrence; Survival Analysis; Transplantation, Autologous

Permanent alopecia after BMT has been reported as a side-effect associated with GVHD or after busulphan conditioning therapy, primarily in adults. We have reviewed children undergoing BMT to document the frequency of incomplete hair regrowth and to evaluate factors associated with this problem. Hair regrowth was studied in 74 children who survived > 6 months following BMT undertaken for malignant and non-malignant diseases. Alopecia was categorised as severe (< 50% of pre-transplant status), moderate (50-75%) or mild (> 75% but less than normal). Overall, 18 (24.3%) of 74 patients had mild (n = 5), moderate (n = 4) or severe (n = 9) alopecia. Risk factors for alopecia were presence of chronic GVHD (67%; p < 0.001), older age (p < 0.001) and prior cranial irradiation (42%; p = 0.03). Alopecia occurred in children receiving either busulphan (31%) or total body irradiation (16%; p = 0.15) as conditioning therapy. The highest frequency was seen in patients conditioned with busulphan with or without melphalan and who received prior cranial irradiation and/or developed chronic GVHD (75%). These data indicate that alopecia after BMT in children is a significant problem and confirm, in children, the previously noted association between alopecia and chronic GVHD and busulphan. Further risk factors of older age and prior cranial irradiation are identified. Consideration needs to be given to the use of an alternative to busulphan in children who are of older age, have received prior cranial irradiation and/or are at increased risk of GVHD.

Topics: Adolescent; Adult; Age Factors; Alopecia; Bone Marrow Purging; Bone Marrow Transplantation; Busulfan; Child, Preschool; Chronic Disease; Cranial Irradiation; Female; Graft vs Host Disease; Hair; Humans; Infant; Leukemia; Male; Melphalan; Radiation Injuries; Risk Factors; Whole-Body Irradiation

Overall 30 patients with multiple myeloma (MM) were examined for immunological and rheological parameters. MM was shown to be marked by imbalance of immunobiological reactivity, with the greatest changes being seen in the B cell immunity system. MM is also characterized by marked rheological shifts related to the immunological alterations and underlying the hyperviscosity syndrome and heart failure. Administration of polychemotherapy resulted in a decrease of the count of B lymphocytes, circulating immune complexes; a tendency toward normalization of the rheological blood properties was observed. Introduction of plasmapheresis into the treatment program of the patients noticeably raised the treatment efficacy.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Viscosity; Chronic Disease; Cyclophosphamide; Daunorubicin; Female; Heart Failure; Humans; Immunity, Cellular; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Nitrogen Mustard Compounds; Prednisolone; Vincristine

Three different programs of polychemotherapy (PCT) of multiple myeloma (MM) were compared. The programs included the use of cyclophosphamide (up to 750 mg/m2), vincristine (1.4 mg/m2), rubomycin (40 mg/m2), sarcolysine (7.5 mg/m2), paphencyl (50 mg/day) and prednisolone (from 30 to 60 mg/m2) in different combinations with regard to the hemocoagulation and rheological blood properties. It has been shown that in patients with MM there occur profound hemocoagulation and rheological alterations playing an important part in the genesis of the syndrome of hyperviscosity and circulation failure. The use of the programs of PCT in conjunction with therapeutic plasmapheresis brought about an appreciable improvement of the patients' general health status and correction of hemocoagulation and hemorheological disorders. To control the efficacy of PCT, its individualization, intensity and duration, it is recommended that in addition to the common tests, the activity of the antithrombin-III-heparin complex may be measured and the test for the presence of fibrin monomer in the plasma be made, since these parameters clearly reflect the changes in the system of hemostasis and enable one to discover the early signs of proliferation activation in MM thereby preventing hemorrhages.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Coagulation; Blood Viscosity; Chronic Disease; Cyclophosphamide; Daunorubicin; Drug Evaluation; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Nitrogen Mustard Compounds; Prednisolone; Vincristine

A case of a 70 years old female who developed multiple myeloma during a course of neutrophilia, and later on terminated with acute monocytic leukemia (AML, M 5 b) following Melphalan therapy for five years is reported. This patient was first found to have neutrophilia in 1966, After six years, she developed monoclonal gammopathy, (IgG1 kappa type) which coexisted with the neutrophilia. She was put on Melphalan regimen for 5 years which was discontinued due to anemia, leukocytopenia and the reduction of serum IgG. By routine bone marrow examination, she was diagnosed as AMoL (AML, M 5 b) in July 1984. Thereafter, a combination chemotherapy of BH-AC, 6-MP and prednisolone was started and complete remission for the AMoL was achieved after 2 months. Sixteen months later, she relapsed and a similar combination chemotherapy for reinduction regimen was administered. However, the AMoL was resistant and after 7 months, she died of pneumonia and multiple organ failure. The association of neutrophilia with multiple myeloma, the occurrence of AMoL after prolonged Melphalan therapy for the multiple myeloma and the strategy of therapy for secondary leukemia is discussed.

Topics: Aged; Chronic Disease; Female; Humans; Leukemia, Monocytic, Acute; Leukocytosis; Melphalan; Multiple Myeloma; Neutrophils

Topics: Antineoplastic Combined Chemotherapy Protocols; Chronic Disease; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Recurrence; Remission Induction

6 patients with chronic cluster headache were treated with lithium carbonate in order to establish the individual lowest effective dose and to assess the possibility of suspending treatment after prolonged administration. Lithium was give at rising doses until more than 90% improvement was obtained. This was achieved in 1 case with only 300 mg daily, in 3 cases with 600 mg and in 2 with 900 mg daily. Of the 5 patients in whom drug administration was suspended 3 had an immediate return of daily attacks of headache, 1 after a 4-month free interval and 1 has maintained the improvement after 6 months without the drug. The sharp decline of the effectiveness of lithium on administration of an antimitotic (Melphalan) provides the starting-point for a discussion on the possible mechanisms of action of lithium in cluster headache.

Topics: Adult; Chronic Disease; Cluster Headache; Drug Therapy, Combination; Female; Humans; Lithium; Lithium Carbonate; Male; Melphalan; Middle Aged; Multiple Myeloma; Vascular Headaches

Topics: Adult; Amyloidosis; Arthritis; Chronic Disease; Female; Humans; Melphalan