melphalan and HIV-Infections

A few prospective trials in HIV-positive patients with Burkitt lymphoma (BL) or high-grade B-cell lymphoma (HGBL) have been reported. Investigated therapies have shown good efficacy but relevant safety problems, with high rates of interruptions, severe mucositis, septic complications, and fungal infections. Here, we report the results of a multicentre phase II trial addressing a new dose-dense, short-term therapy aimed at maintaining efficacy and improving tolerability. The experimental programme included a 36-day polychemotherapy induction followed by high-dose cytarabine-based consolidation and response-tailored BEAM (carmustine, etoposide, cyatarabine, and melphalan)- conditioned autologous stem cell transplantation (ASCT). This therapy would be considered active if ≥11 complete remissions (CR) after induction (primary endpoint) were recorded among 20 assessable patients. HIV-positive adults (median age 42, range 26-58; 16 males) with untreated BL (n = 16), HGBL (n = 3) or double-hit lymphoma (n = 1) were enrolled. All patients had high-risk features, with meningeal and bone marrow infiltration in five and nine patients respectively. The experimental programme was safe and active in a multicentre setting, with only two episodes of grade 4 non-haematological toxicity (hepatotoxicity and mucositis), and no cases of systemic fungal infections; two patients died of toxicity (bacterial infections). Response after induction (median duration: 47 days; interquartile range 41-54), was complete in 13 patients and partial in five [overall response rate = 90%; 95% confidence interval (CI) = 77-100]. All responders received consolidation, and five required autologous stem cell transplant. At a median follow-up of 55 (41-89) months, 14 patients are relapse-free and 15 are alive, with a five-year progression-free survival and an overall survival of 70% (95% CI = 60-80%) and 75% (95% CI = 66-84) respectively. No patient with cerebrospinal fluid (CSF)/meningeal lymphoma experienced central nervous system recurrence. With respect to previously reported regimens, this programme was delivered in a shorter period, and achieved the main goal of maintaining efficacy and improving tolerability.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Burkitt Lymphoma; Carmustine; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; HIV Infections; Humans; Lymphoma, B-Cell; Male; Melphalan; Middle Aged; Transplantation, Autologous

Burkitt lymphoma is an aggressive B cell malignancy accounting for 1-2% of all adult lymphomas. Treatment with dose-intensive, multi-agent chemotherapy is effective but associated with considerable toxicity. In this observational study, we compared real-world efficacy, toxicity, and costs of four frequently employed treatment strategies for Burkitt lymphoma: the Lymphome Malins B (LMB), the Berlin-Frankfurt-Münster (BFM), the HOVON, and the CODOX-M/IVAC regimens. We collected data from 147 adult patients treated in eight referral centers. Following central pathology assessment, 105 of these cases were accepted as Burkitt lymphoma, resulting in the following treatment groups: LMB 36 patients, BFM 19 patients, HOVON 29 patients, and CODOX-M/IVAC 21 patients (median age 39 years, range 14-74; mean duration of follow-up 47 months). There was no significant difference between age, sex ratio, disease stage, or percentage HIV-positive patients between the treatment groups. Five-year progression-free survival (69%, p = 0.966) and 5-year overall survival (69%, p = 0.981) were comparable for all treatment groups. Treatment-related toxicity was also comparable with only hepatotoxicity seen more frequently in the CODOX/M-IVAC group (p = 0.004). Costs were determined by the number of rituximab gifts and the number of inpatients days. Overall, CODOX-M/IVAC had the most beneficial profile with regards to costs, treatment duration, and percentage of patients completing planned treatment. We conclude that the four treatment protocols for Burkitt lymphoma yield nearly identical results with regards to efficacy and safety but differ in treatment duration and costs. These differences may help guide future choice of treatment.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Carmustine; Cost-Benefit Analysis; Cyclophosphamide; Cytarabine; Etoposide; Female; HIV Infections; Humans; Ifosfamide; Male; Melphalan; Methotrexate; Middle Aged; Neoplasm Staging; Retrospective Studies; Rituximab; Survival Analysis

Emerging data relating to human immunodeficiency virus type 1 (HIV-1) cure suggest that vaccination to stimulate the host immune response, particularly cytotoxic cells, may be critical to clearing of reactivated HIV-1-infected cells. However, evidence for this approach in humans is lacking, and parameters required for a vaccine are unknown because opportunities to study HIV-1 reactivation are rare.. We present observations from a HIV-1 elite controller, not treated with combination antiretroviral therapy, who experienced viral reactivation following treatment for myeloma with melphalan and autologous stem cell transplantation. Mathematical modeling was performed using a standard viral dynamic model. Enzyme-linked immunospot, intracellular cytokine staining, and tetramer staining were performed on peripheral blood mononuclear cells; in vitro CD8 T-cell-mediated control of virion production by autologous CD4 T cells was quantified; and neutralizing antibody titers were measured.. Viral rebound was measured at 28,000 copies/mL on day 13 post-transplant before rapid decay to <50 copies/mL in 2 distinct phases with t1/2 of 0.71 days and 4.1 days. These kinetics were consistent with an expansion of cytotoxic effector cells and killing of productively infected CD4 T cells. Following transplantation, innate immune cells, including natural killer cells, recovered with virus rebound. However, most striking was the expansion of highly functional HIV-1-specific cytotoxic CD8 T cells, at numbers consistent with those applied in modeling, as virus control was regained.. These observations provide evidence that the human immune response is capable of controlling coordinated global HIV-1 reactivation, remarkably with potency equivalent to combination antiretroviral therapy. These data will inform design of vaccines for use in HIV-1 curative interventions.

Topics: Antibodies, Neutralizing; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cytokines; Enzyme-Linked Immunospot Assay; HIV Antibodies; HIV Infections; HIV-1; Humans; Leukocytes, Mononuclear; Melphalan; Middle Aged; Models, Theoretical; Multiple Myeloma; Myeloablative Agonists; Stem Cell Transplantation; T-Lymphocyte Subsets; Transplantation, Autologous; Virus Activation

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

HIV infection rages at the endemic state in Sub Saharan African and especially in Congo Brazzaville. We report the observation of three female patients infected with HIV and developing multiple myeloma. The three patients were treated at the University hospital of Brazzaville between 2000 and 2002. In two cases multiple myeloma was discovered after the diagnosis of HIV infection. In the other case, the diagnosis of HIV infection was posterior to the occurrence of multiple myeloma. HIV infection was symptomatic in two cases who received consequently antiviral treatment. Multiple myeloma was diagnosed at an advanced stage in the three cases. The paraprotein was an IgG in two cases and an IgA in the other one. The CD4 counts before treatment were around 200/mm3 in two cases and within normal limits in the third case. Viral load was not measured. VMCP and VAMCP regimens were administered without major complications and under anti-infectious prophylaxis. The follow-up is still insufficient to assess the medium-term evolution and to determine the prognosis of multiple myeloma. The description of these three cases confirms the involvement of HIV in B cell lymphoma genesis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; HIV Infections; Humans; Immunoglobulin A; Immunoglobulin G; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Vincristine