melphalan and Bacterial-Infections

Topics: Alkylating Agents; Amyloidosis; Anemia; Anemia, Refractory; Animals; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Blood Transfusion; Bone and Bones; Bone Marrow Examination; Bone Marrow Transplantation; Bone Neoplasms; Calcium; Combined Modality Therapy; Diagnosis, Differential; Heavy Chain Disease; Humans; Immunoglobulin D; Immunotherapy; Interferons; Kidney Failure, Chronic; Leukemia; Melphalan; Mice; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Myeloma Proteins; Osteolysis; Osteosclerosis; Paraproteinemias; Plasma Cells; Plasmacytoma; Prednisone; Radionuclide Imaging; Waldenstrom Macroglobulinemia

Pharmacokinetic modeling has suggested, and clinical investigations have confirmed, that intracavitary drug administration can result in a much greater drug exposure for the cavity into which the agent is instilled compared to the plasma. Both the safety and the efficacy of several agents administered individually or in combination have now been demonstrated. Several malignancies, in particular ovarian carcinoma and malignant mesothelioma, which remain confined to body cavities for much of their natural history, might be most rationally treated by the intracavitary treatment approach. Early clinical trials have demonstrated significant activity of intracavitary chemotherapy in both of these malignancies. Optimal drugs and dosages as well as appropriate scheduling for the various tumors involving body cavities remain to be defined. Whether or not combination intracavitary chemotherapy will significantly improve survival of patients with malignant disease confined to body cavities must await carefully controlled clinical trials comparing this treatment approach to standard systemically administered chemotherapy.

Topics: Absorption; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascitic Fluid; Bacterial Infections; Bleomycin; Cisplatin; Cytarabine; Diffusion; Doxorubicin; Drug Synergism; Female; Fluorouracil; Humans; Immunotherapy; Melphalan; Methotrexate; Mitomycins; Neoplasms; Ovarian Neoplasms; Peritoneal Cavity; Permeability; Pleura; Pleural Effusion; Radiation-Sensitizing Agents; Sclerosis; Streptozocin

Topics: Acute Kidney Injury; Altretamine; Anemia; Bacterial Infections; Bone Neoplasms; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Hypercalcemia; Interferons; Kidney Failure, Chronic; Melphalan; Meningeal Neoplasms; Multiple Myeloma; Spinal Cord Compression; Vinblastine; Vincristine; Vindesine

The basic pathologic process in multiple myeloma is the neoplastic proliferation of a single clone of plasma cells. Although the events which trigger autonomous cell growth are not well understood, the secretion of an M component, a serum or urinary immunoglobulin molecule or a light chain fragment by the vast majority of myeloma cells has provided a biologic marker which has greatly facilitated the study of this disease Some of the more recent clinical concepts which have evolved from studies on the plasma cell and the immunoglobulin molecule are discussed.

Topics: Alkylating Agents; Amyloidosis; Bacterial Infections; Blood Viscosity; Bone Diseases; Clone Cells; Hemostasis; Humans; Hypercalcemia; Kidney Failure, Chronic; Melphalan; Multiple Myeloma; Paraproteins

Whether the intensity of the conditioning regimen affects febrile neutropenia (FN) and severe bacterial infections (SBIs) is not well established. We analyzed the risk factors (RFs) for the development of FN and SBI in the first 100d post-transplant in 195 consecutive adult recipients of a reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC-allo).. The RIC regimens consisted of fludarabine plus melphalan (62%) or busulphan (38%) (FluMel or FluBu). SBIs include pneumonia, urinary tract infections, and bacteremia.. FN occurred in 141 patients (72%), always in the first 30d post-allo-RIC. However, a SBI occurred in only 27 patients (14%) during this early post-transplant period (

Topics: Adult; Bacterial Infections; Busulfan; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Melphalan; Middle Aged; Mucositis; Mycophenolic Acid; Myeloablative Agonists; Neutropenia; Retrospective Studies; Risk Factors; Time Factors; Transplantation Conditioning; Transplantation, Homologous

This study was designed to evaluate the efficacy of therapeutic intensification with autologous stem cell transplantation (ASCT) for mantle cell lymphomas (MCL) in terms of response rate, duration of response, and event-free and overall survivals. Twenty-four patients with confirmed MCL responding to chemotherapy received a high-dose chemo-radiotherapy regimen followed by ASCT. Transplantation was performed during first-line therapy in nine cases, second-line in 13 cases and third-line in two cases. The source of hematopoietic stem cells was peripheral blood for 19 cases. At the time of ASCT, eight patients were in complete remission (33%). Seventeen of the 24 cases received an intensified regimen with TBI and seven received the BEAM or the BEAC regimen. After transplantation, 19 patients were in CR (79%). Nine of these were alive in continued CR at a median follow-up of 34 months, while seven relapsed at a median of 18 months. One patient died from Pneumocystis carinii interstitial pneumonitis and five patients developed secondary malignancies. With a median follow-up after transplantation of 34 months, the 3-year event-free survival was 55% and the 3-year overall survival was 68%. These results indicate that therapeutic intensification with ASCT might be an effective treatment for mantle cell lymphomas. Bone Marrow Transplantation (2000) 25, 251-256.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Etoposide; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Mantle-Cell; Male; Melphalan; Middle Aged; Neoplasms, Second Primary; Recurrence; Survival Rate; Transplantation, Autologous; Treatment Outcome; Whole-Body Irradiation

This study aimed to compare clinical outcomes of chemotherapy patients who received either a neutropenic diet (ND) or liberalised diet (LD) and to investigate associations between ND and infectious outcomes.. A retrospective case note audit of patients admitted to Flinders Medical Centre from 2013 to 2017 was conducted. Patients were eligible if they were aged 18 years and above, received chemotherapy and were neutropenic during admission. Demographic and clinical data were collected from medical records. Primary outcomes were occurrence of infections and fever. Secondary outcomes include hospital length of stay and infection-related mortality.. Seventy-nine patients received ND while 75 patients received LD. The ND group had more patients with acute myeloid leukaemia (p < .001) and receiving high-toxicity chemotherapy (p = .005). Incidence of febrile neutropenia (p = .016), bacteraemia (p = .044) and number of febrile days (p = .033) was higher in the ND group. ND was not independently associated with occurrence of febrile neutropenia or infections. Subsample analysis of 20 pairs of patients matched on age, sex and cancer diagnosis found no significant differences in clinical outcomes between groups.. ND was not associated with the prevention of adverse outcomes in chemotherapy patients.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Bacterial Infections; Carmustine; Chemotherapy-Induced Febrile Neutropenia; Cytarabine; Diet Therapy; Enterocolitis, Neutropenic; Female; Hematologic Neoplasms; Humans; Idarubicin; Male; Melphalan; Middle Aged; Neutropenia; Podophyllotoxin; Retrospective Studies; South Australia

Immunoglobulin light chain (AL) amyloidosis can be treated with high-dose melphalan and autologous stem cell transplantation (HDM/SCT). Risk factors for infections may include hyposplenism, hypogammaglobulinemia, treatment-related neutropenia, melphalan-induced mucositis, and nosocomial exposures.. A review of 493 patients with AL amyloidosis undergoing treatment with HDM/SCT from August 1994 to August 2009 was performed. The objectives were to determine the rate and types of infections following HDM/SCT, to identify factors associated with microbiologically documented infections, and to assess the contribution of infections to all-cause treatment-related mortality (TRM; defined as deaths within 100 days of SCT).. Microbiologically documented infections after HDM/SCT occurred in 24% (n = 119) of patients. TRM was 10% (n = 48) overall, and 21% (n = 25) in patients who had a documented infection. Thus, the relative risk of TRM in a patient with a documented infection was 3.42 (95% confidence interval [CI] 2.02-5.79). Infections were caused by gram-positive bacteria in 51%, anaerobic bacteria in 16%, gram-negative bacteria in 13%, and fungi in 9% of cases. Serum creatinine >2 mg/dL was associated with increased risk of post-SCT infection (38% vs. 21%, P = 0.0007) with an odds ratio of 2.27 (95% CI 1.40-3.68). No significant association for infection was found for age, gender, cardiac involvement, prior steroid therapy, dose of melphalan, multiorgan involvement, days to neutrophil engraftment, or dose of CD34 +  cells infused.. Serum creatinine >2 mg/dL is a risk factor for infections in patients with AL amyloidosis undergoing HDM/SCT. The relative risk of TRM in a patient with a documented infection was increased >3-fold. A broad spectrum of infections, similar to that in other SCT patients, is seen in this population in the early post-SCT period.

Topics: Aged; Aged, 80 and over; Amyloidosis; Bacterial Infections; Combined Modality Therapy; Cross Infection; Dose-Response Relationship, Drug; Female; Humans; Immunoglobulin Light Chains; Male; Melphalan; Middle Aged; Mycoses; Myeloablative Agonists; Postoperative Complications; Risk Factors; Stem Cell Transplantation; Transplantation, Autologous

Liver injury is a common complication in allogeneic hematopoietic stem cell transplantation. Its major causes comprise graft-versus-host disease (GVHD), infection, and toxicities of preparative regimens and immunosuppressants; however, we have little information on liver injuries after reduced intensity cord blood transplantation (RICBT). We reviewed medical records of 104 recipients who underwent RICBT between March 2002 and May 2004 at Toranomon Hospital. Preparative regimen and GVHD prophylaxis comprised fludarabine/melphalan/total body irradiation and cyclosporine or tacrolimus. We assessed the etiology of liver injuries based on the clinical presentation, laboratory results, comorbid events, and imaging studies in 85 patients who achieved primary engraftment. The severity of liver dysfunction was assessed according to the National Cancer Institute Common Toxicity Criteria version 2.0. Hyperbilirubinemia was graded according to a report by Hogan et al (Blood. 2004;103:78-84). Moderate to very severe liver injuries were observed in 36 patients. Their causes included cholestatic liver disease (CLD) related to GVHD or sepsis (n = 15), GVHD (n = 7), cholangitis lenta (n = 5), and others (n = 9). Median onsets of CLD, GVHD, and cholangitis lenta were days 37, 40, and 22, respectively. Frequencies of grade 3-4 alanine aminotransferase elevation were comparable across the 3 types of hepatic injuries. Serum gamma-glutamil transpeptidase was not elevated in any patients with cholangitis lenta, whereas 27% and 40% of patients with CLD and GVHD, respectively, developed grade 3-4 gamma-glutamil transpeptidase elevation. Multivariate analysis identified 2 risk factors for hyperbilirubinemia; grade II-IV acute GVHD (relative risk, 2.23; 95% confidential interval, 1.11-4.47; P = .024) and blood stream infection (relative risk, 3.77; 95% confidential interval, 1.91-7.44; P = .00013). In conclusion, the present study has demonstrated that the hepatic injuries are significant problems after RICBT, and that GVHD and blood stream infection contribute to their pathogenesis.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Busulfan; Chemical and Drug Induced Liver Injury; Cholangitis; Cord Blood Stem Cell Transplantation; Cyclosporine; Female; Hematologic Diseases; Hematologic Neoplasms; Hepatic Veno-Occlusive Disease; Humans; Hyperbilirubinemia; Immunosuppressive Agents; Incidence; Infant, Newborn; Liver Diseases; Liver Function Tests; Male; Melphalan; Middle Aged; Postoperative Complications; Risk Factors; Tacrolimus; Tissue Donors; Transplantation Conditioning; Vidarabine; Whole-Body Irradiation

Seventeen patients were treated with high-dose melphalan with autologous bone marrow transplant (ABMT) and cyclophosphamide pretreatment. All of the patients had marrow reconstitution. Although there was one death caused by infection, high-dose melphalan with ABMT causes toxicity that is generally acceptable, and can achieve a high-response rate, but with responses of short duration in tumors resistant to standard-dose combination chemotherapy. In other poor-prognosis tumors that are sensitive to chemotherapy, or can be debulked surgically, or locally irradiated, high-dose melphalan with ABMT given as late intensification therapy may significantly prolong time to relapse, and ultimately prolong survival.

Topics: Adult; Bacterial Infections; Bone Marrow Transplantation; Combined Modality Therapy; Cyclophosphamide; Female; Humans; Male; Melphalan; Middle Aged; Myeloproliferative Disorders; Neoplasms; Prognosis; Vomiting

Patients with asymptomatic or smoldering multiple myeloma should not be treated but should be observed closely for progression. For symptomatic myeloma, chemotherapy is indicated. Melphalan, the agent of choice, should be given with prednisone for 1 week of every 6 weeks, If melphalan brings no response, or response and then relapse, cyclophosphamide (Cytoxan) should be give intravenously every 4 weeks or orally every day. BCNU, CCNU, and doxorubicin (Adriamycin) have also shown activity in myeloma. Hypercalcemia occurs in one-third of patients and should be countered with hydration, corticosteroids, Neutra-Phos, or mithramycin. Long-term hemodialysis has achieved some success. The combination of sodium flouride and calcium carbonate produces new bone formation; it seems a useful adjunct in treatment for myelomatous bone disease. Radiation should be utilized only for severe, localized pain or for solitary lesions. Survival with multiple myeloma varies, mean durations being 2 to 3 years. Multivariate analysis indicates that serum creatinine and calcium levels are the most significant indicators regarding 2-year survival. We have found monoclonal proteinuria not significantly more frequent with renal insufficiency than with normal renal function, renal insufficiency not significantly more frequent with lambda than with kappa chains, and survival not significantly greater with IgG myeloma than with IgA.

Topics: Anemia; Bacterial Infections; BCG Vaccine; Carmustine; Cyclophosphamide; Fractures, Bone; Humans; Hypercalcemia; Kidney Failure, Chronic; Melphalan; Multiple Myeloma; Mycobacterium bovis; Prognosis

Management of some diverse complications of plasma cell myeloma is reviewed with respect to prevention when possible and prompt treatment when necessary. A series of 102 patients from the Duke University Medical Center was surveyed to ascertain the approximate frequency with which renal failure, hypercalcemia, infection, hyperviscosity syndrome, and neurologic disorders occur. Selected patient studies and additional data from the literature emphasize aspects of these complications amenable to therapy aside from that directed at plasma cell growth.

Topics: Acute Kidney Injury; Bacterial Infections; Blood Urea Nitrogen; Blood Viscosity; Bone Neoplasms; Cephalothin; Cyclophosphamide; Cytarabine; Female; Fluoxymesterone; Furosemide; Gentamicins; Humans; Hypercalcemia; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Neurologic Manifestations; Plicamycin; Renal Dialysis