melphalan and Lung-Diseases

Intensive therapy and autologous marrow or peripheral blood stem cell transplantation is often utilized in Hodgkin's disease patients whose disease has progressed after primary conventional chemotherapy. A number of studies have described long-term disease-free survival in up to 50% of transplanted patients. High-dose chemotherapy conditioning regimens such as "CBV" or "BEAM" have been used more often than regimens containing total body irradiation. Usually unpurged autologous bone marrow has been utilized as the source of hematopoietic stem cell reconstitution, although recently the use of "primed" peripheral blood stem cells has increased markedly. The challenges of transplant-related toxicity and recurrence of disease post-transplant are discussed, as well as possible strategies to reduce these problems. The use of autologous transplantation is discussed in three clinical settings: patients who have failed to enter a complete remission (CR) after primary chemotherapy, those who have relapsed within 12 months of attaining a CR and those who have relapsed after a longer (i.e., > or = 12 months) first CR. When compared with conventional salvage chemotherapy, transplantation appears to produce a higher long-term disease-free survival rate in all of these patient groups. However, assessment of an advantage for autotransplantation, particularly in patients with long first remissions, is difficult without a Phase III trial. On the other hand, recently updated results from our center indicate that 72% of patients relapsing after long initial remissions benefit from autotransplantation at this point in their disease course, and that transplant-related mortality is low in this setting. Other issues addressed include the potential role of autologous transplantation as consolidation therapy in selected high-risk patients in an initial CR, as well as the utility of conventional chemotherapy and involved-field radiotherapy in conjunction with autotransplantation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Bone Marrow Transplantation; Carmustine; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Digestive System Diseases; Etoposide; Heart Diseases; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lung Diseases; Melphalan; Multicenter Studies as Topic; Podophyllotoxin; Recurrence; Remission Induction; Salvage Therapy; Survival Rate; Treatment Outcome; Whole-Body Irradiation

Autologous stem cell transplantation (SCT) with high-dose melphalan (HDM, 200 mg/m2) is the most effective therapy for multiple myeloma. To determine the feasibility of combining carmustine (300 mg/m2) with HDM, we enrolled 49 patients with previously treated Durie-Salmon stage II/III myeloma (32M/17W, median age 53) on a phase I/II trial involving escalating doses of melphalan (160, 180, 200 mg/m2). The median beta2-microglobulin was 2.5 (0-9.3); marrow karyotypes were normal in 88%. The phase I dose-limiting toxicity was > or =grade 2 pulmonary toxicity 2 months post-SCT. Other endpoints were response rate and progression-free survival (PFS). HDM was safely escalated to 200 mg/m2; treatment-related mortality was 2% and > or =grade 2 pulmonary toxicity 10%. The complete (CR) and near complete (nCR) response rate was 49%. With a median post-SCT follow-up of 2.9 years, the PFS and overall survival (OS) post-SCT were 2.3 and 4.7 years. PFS for those with CR or nCR was 3.1 years while for those with stable disease (SD) it was 1.3 years (P=0.06). We conclude that carmustine can be combined with HDM for myeloma with minimal pulmonary toxicity and a high response rate.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Lung Diseases; Male; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Recurrence; Survival Analysis; Transplantation, Autologous

Sixty-five patients with hematological malignancies (25 multiple myeloma, 18 Hodgkin's disease, 22 non-Hodgkin's lymphomas) who received a carmustine-based regimen followed by autologous PBPC transplantation, were studied retrospectively to evaluate the incidence of post-transplant non-infective pulmonary complications (NIPCs), risk factors predictive of NIPCs, and response to steroids. Carmustine (BCNU) given i.v. at a dose of 600 mg/m2 was combined with etoposide and cyclophosphamide in 40 patients (BCV regimen) and with etoposide and melphalan in 25 patients (BEM regimen). Seventeen of 65 patients (26%) had one episode of NIPCs. The median time to NIPCs was 90 days (52-289). Factors that increased the risk of developing NIPCs on multivariate analysis were female sex (P < 0. 001) and BCV regimen (P < 0.05). All patients with NIPCs received prednisone at a dose of 1 mg/kg body weight for 10 days then tapered by 5 mg every two days; complete response to steroids was achieved in 15 of 17 patients; one unresponsive patient died of interstitial pneumonia. BCNU given at the dose of 600 mg/m2 is well tolerated when associated with melphalan and etoposide. In females and in patients receiving BCNU with cyclophosphamide, a BCNU dose reduction may be advisable. Bone Marrow Transplantation (2000) 25, 309-313.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Etoposide; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Infant; Infections; Lung Diseases; Male; Melphalan; Middle Aged; Retrospective Studies; Transplantation, Autologous

Forty patients (median age, 31 years; range, 20 to 63) with Hodgkin lymphoma underwent an allogeneic stem cell transplant with the gemcitabine-fludarabine-melphalan reduced-intensity conditioning regimen. Thirty-one patients (77%) had undergone a prior autologous stem cell transplant, with a median time to progression after transplant of 6 months (range, 1 to 68). Disease status at transplant was complete remission/complete remission, undetermined (n = 23; 57%), partial remission (n = 14; 35%), and other (n = 3; 8%). Twenty-six patients (65%) received brentuximab vedotin before allotransplant. The overall complete response rate before allotransplant was 65% in brentuximab-treated patients versus 42% in brentuximab-naive patients (P = .15). At the latest follow-up (October 2015) 31 patients were alive. The median follow-up was 41 months (range, 5 to 87). Transplant-related mortality rate at 3 years was 17%. Pulmonary, skin toxicities, and nausea were seen in 13 (33%), 11 (28%), and 37 (93%) patients, respectively. At 3 years, estimates for overall and progression-free survival were 75% (95% CI, 57% to 86%) and 54% (95% CI, 36% to 70%). Overall incidence for disease progression was 28% (95% CI, 16% to 50%). We believe the gemcitabine-fludarabine-melphalan regimen allows moderate dose intensification with acceptable morbidity and mortality. The inclusion of gemcitabine affected nausea, pulmonary, and likely skin toxicity. Exposure to brentuximab vedotin allowed more patients to reach allogeneic stem cell transplantation in complete remission. With over 50% of patients progression-free at 3 years, allogeneic stem cell transplantation with reduced-intensity conditioning remains an effective and relevant treatment option for Hodgkin lymphoma in the brentuximab vedotin era.

Topics: Adult; Brentuximab Vedotin; Deoxycytidine; Female; Gemcitabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Immunoconjugates; Lung Diseases; Male; Melphalan; Middle Aged; Nausea; Remission Induction; Salvage Therapy; Skin Diseases; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Young Adult

Pulmonary Langerhans histiocytosis (PLH) is a rare disease due to the accumulation of Langerhans cells at the level of the bronchioles. These dendritic immunocytes form granulomata and destroy the wall of the airway. We report a case of PLH developing at the same time as Hodgkin's lymphoma in a young woman who smoked tobacco and cannabis. We observed a complete remission of the PLH lesions parallel to the remission of the Hodgkin's lymphoma after chemotherapy, in the absence of any change in the consumption of tobacco and cannabis. This observation leads us to discuss the potential relationships between PLH on one hand, and smoking, the lymphoma and its treatment on the other.

Topics: Accidents, Traffic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bronchioles; Carmustine; Cytarabine; Dacarbazine; Doxorubicin; Etoposide; Female; Histiocytosis, Langerhans-Cell; Hodgkin Disease; Humans; Ifosfamide; Incidental Findings; Lung Diseases; Lymphatic Diseases; Marijuana Smoking; Melphalan; Methylprednisolone; Mitoguazone; Remission Induction; Smoking; Tomography, X-Ray Computed; Vinblastine; Vindesine; Vinorelbine; Young Adult

Simultaneous bilateral spontaneous pneumothorax (SBSP) during high-dose chemotherapy has been described in patients with pulmonary involvement by malignancy, including sarcoma, trophoblastic tumor, non-seminomatous testicular cancer, and non-Hodgkin lymphoma. We present a case of SBSP developing in a patient 11 days after a high-dose chemotherapy preparative regimen and stem cell transplantation without underlying pulmonary disease or evidence of lung lesions. It is important to recognize spontaneous pneumothorax as a potential complication of high-dose chemotherapy, especially in patients with known pulmonary lesions.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Cytarabine; Etoposide; Female; Humans; Lung Diseases; Lymphoma, Mantle-Cell; Melphalan; Middle Aged; Pneumothorax; Prognosis

We describe a case of a systemic amyloidosis of kappa-AL type, presenting at CT as focal lung parenchymal nodules or areas of consolidation with or without a halo,showing different sizes and morphologic kinetics at follow-up. Lesions accompanied by a halo revealed faster progression and earlier response to chemotherapy with almost complete resolution after high dose therapy with a cytostatic alkylating agent(Melphalan) and autologous peripheral stem cell transplantation than their counterparts without a halo. Amyloid deposition was histologically confirmed, and severe inflammatory activity was found in and at the margins of the amyloidomas, the latter correlating in CT with the halo sign. In our case, this sign had a high prediction for growth kinetics and response to therapy of pulmonary amyloid.

Topics: Amyloid; Amyloidosis; Disease Progression; Follow-Up Studies; Forecasting; Humans; Immunoglobulin kappa-Chains; Lung Diseases; Male; Melphalan; Middle Aged; Myeloablative Agonists; Peripheral Blood Stem Cell Transplantation; Remission Induction; Tomography, X-Ray Computed; Treatment Outcome

We describe here an extremely rare case of primary amyloidosis which presented moderate pleural effusion and high fever. A 71-year-old man was admitted to our hospital because of exertional dyspnea, fatigue and fever. A chest X-ray showed right-sided moderate pleural effusion. A thoracocentesis revealed an exudative pleural effusion. Cytology and cultures of the effusion were negative. External drainage failed to control the effusion. To determine the etiology of the effusion and fever, bronchoscopy was performed. Biopsies of the tracheal wall showed amyloid deposition. The pleural effusion might have been due to the inflammation and the disturbed lymphatic drainage caused by the amyloid deposition. Treatment with melphalan (6 mg) and prednisolone (35 mg) for 4 days every 6 weeks decreased the fever and alleviated his symptoms.

Topics: Aged; Amyloidosis; Anti-Inflammatory Agents; Antineoplastic Agents, Alkylating; Bronchoscopy; Dyspnea; Exudates and Transudates; Fever; Humans; Lung Diseases; Male; Melphalan; Pleural Effusion; Prednisolone; Treatment Outcome

Topics: Antineoplastic Agents, Alkylating; Drug Administration Schedule; Hematopoietic Stem Cell Transplantation; Humans; Lung Diseases; Melphalan; Multiple Myeloma; Probability; Transplantation, Autologous

A 56 year-old woman was admitted due to exertional dyspnoea. Her chest x-ray and CT scanning showed widespread diffuse infiltrative changes in both lungs, associated with a pronounced decrease in diffusion capacity. Transbronchial biopsies showed primary (AL) amyloidosis. Systemic AL-amyloidosis was excluded and diagnosis of localised diffuse parenchymal pulmonary amyloidosis was established. Treatment with prednisolone and melphalan for one year has stabilised the condition. Lung transplantation will be considered in case of deterioration.

Topics: Amyloidosis; Anti-Inflammatory Agents; Female; Humans; Lung; Lung Diseases; Melphalan; Middle Aged; Prednisolone; Tomography, X-Ray Computed

A-52-year-old patient presented with a 2-year history of multiple myeloma, recurrent episodes of hypercalcemia, and extensive bone involvement. She developed pulmonary infiltrates, initially misdiagnosed as interstitial pneumonia. High-resolution computed tomography and bone scintiscanning indicated pulmonary calcification, which was confirmed by a transbronchial biopsy. Cytostatic treatment of multiple myeloma in combination with repetitive i.v. administration of bisphosphonates over a period of 6 months led to a significant improvement of clinical symptoms. Regression of pulmonary infiltrates was demonstrated by chest radiograph and computed tomography. There are only a few reports on pulmonary calcification in patients with multiple myeloma; the condition was associated mostly with progressive disease, kidney failure, adult respiratory distress syndrome and bad prognosis. In our patient isolated calcification of the lungs without involvement of other organ systems was successfully treated. These findings suggest that interstitial pulmonary calcinosis in multiple myeloma can be reversed by normalization of serum calcium levels using bisphosphonates combined with cytostatic treatment.

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Calcinosis; Diphosphonates; Female; Humans; Lung Diseases; Melphalan; Middle Aged; Multiple Myeloma; Pamidronate; Prednisone; Tomography, X-Ray Computed

High-dose chemotherapy with BCNU, melphalan, or both, followed by autologous bone marrow transplantation (ABMT) has been reported to produce response rates in excess of 60% in patients with advanced melanoma. We tested doses of BCNU associated with reversible bone marrow toxicity and acceptable extramedullary toxicity without the use of ABMT in 19 patients with a diagnosis of advanced malignant melanoma. All patients were evaluable for toxicity and 18 were evaluable for response; one patient had a new primary tumor. The patient population had a median age of 44 years (range, 16 to 71) and a median Karnofsky performance status of 80 (range, 50 to 100). Ten were women and nine were men, all had visceral dominant disease, and none had received previous chemotherapy. Our purpose was to test the feasibility of treatment without ABMT, its toxicity and efficacy, and the possibility of administering sequential repeated courses of therapy. Vincristine was added to the regimen to potentially increase efficacy. Treatment consisted of BCNU (750 mg/m2) and vincristine (2 mg days 1 and 8). Six patients who recovered bone marrow function received melphalan (60 mg/m2) and vincristine (2 mg days 1 and 8). Twenty-two percent (95% confidence limits, 3% to 39%) of patients had remissions (all partial) and these were of short duration. Toxicity was substantial with 16% early lethality and 29% incidence of lethal drug-related complications. Two patients (11%) died toxic after a second course of BCNU. Our results suggest that there is no practical role for high-dose BCNU in the treatment of melanoma.

Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Bone Marrow Transplantation; Carmustine; Central Nervous System Diseases; Drug Administration Schedule; Female; Humans; Lung Diseases; Male; Melanoma; Melphalan; Middle Aged; Thrombocytopenia; Vincristine

Topics: Amyloidosis; Dimethyl Sulfoxide; Humans; Lung Diseases; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisolone; Pulmonary Alveoli

Topics: Amyloidosis; Autopsy; Bone and Bones; Carbon Dioxide; Coronary Vessels; Female; Humans; Lung; Lung Diseases; Melphalan; Middle Aged; Multiple Myeloma; Myocardium; Oxygen; Pulmonary Ventilation; Respiration; Spirometry; Vital Capacity