melphalan and Cytomegalovirus-Infections

Cytomegalovirus (CMV) is an important pathogen after allogeneic transplantation. However, few studies have examined CMV reactivation after autologous peripheral blood stem cell transplantation (APBSCT) to treat multiple myeloma (MM), especially in the setting of the newer chemotherapeutic agents and/or 2 sequential APBSCTs (ie, tandem transplantation). A retrospective chart review of patients with MM who underwent either single APBSCT or tandem transplantation was conducted to evaluate the incidence, risk factors, and outcomes of CMV infection at a single institution. A total of 104 patients with MM underwent transplantation during the study period, including 66 patients who received tandem transplantation. The majority of patients (66 of 104; 63.5%) were CMV-seropositive, and CMV viremia was frequently detected in this subgroup (32 of 66; 48.5%). No primary CMV infections were identified. CMV reactivation was more common in recipients of tandem transplantation than in recipients of single APBSCT (P < .001). In addition, patients who developed CMV viremia were more likely to have received conditioning therapy with melphalan, bortezomib, dexamethasone, and thalidomide compared with those without CMV reactivation (P = .015). However, on multiple logistic regression analysis, only receipt of tandem transplantation was significantly associated with CMV reactivation (odds ratio, 5.112; 95% confidence interval, 1.27-20.60; P = .022). Febrile episodes of CMV viremia were observed in 17 patients (17 of 32; 53.1%), and invasive CMV disease was diagnosed in 1 patient. Our data suggest that CMV reactivation after APBSCT for MM is relatively common, and that viremia is often associated with fever. CMV surveillance should be considered, especially when tandem transplantation is performed using combination chemotherapy with high-dose melphalan.

Topics: Aged; Antiviral Agents; Boronic Acids; Bortezomib; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Peripheral Blood Stem Cell Transplantation; Pyrazines; Retrospective Studies; Risk Factors; Thalidomide; Transplantation Conditioning; Transplantation, Autologous; Viral Load; Viremia; Virus Activation

Human cytomegalovirus (HCMV) reactivation can cause a wide range of complications in hematopoietic stem cell transplant recipients, ranging from pneumonia to graft failure. Although reactivations are usually seen in the early post-transplant period, ongoing and untreated HCMV reactivation at the time of high-dose chemotherapy and autologous stem cell support is an exceedingly rare circumstance whose consequences remain largely unknown. This case report describes a patient who underwent high-dose melphalan and autologous transplantation with unknown active HCMV replication.

Topics: Antineoplastic Agents, Alkylating; Cytomegalovirus; Cytomegalovirus Infections; Fatal Outcome; Humans; Male; Melphalan; Middle Aged; Stem Cell Transplantation; Transplantation, Autologous; Virus Activation

Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Cytomegalovirus; Cytomegalovirus Infections; Humans; Incidence; Melphalan; Peripheral Blood Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Virus Activation; Whole-Body Irradiation

Tandem autologous transplant actually represents a challenge in multiple myeloma treatment, but the best conditioning regimen is still under investigation. With the aim of evaluating the feasibility of a modified tandem transplant strategy, we treated 10 multiple myeloma patients after conventional first line chemotherapy with a two step conditioning regimen consisting of high-dose melphalan (200 mg/m2) followed by high-dose melphalan (180 mg/m2) together with indarubicin (15 mg/sqm2 c.i. x 3 days) both with peripheral stem cell support. At first transplant, the median age wasyears, performance status was good and disease status was CR in 2 patients and PR in the rest. At the end of the first transplant, 70% of patients achieved CR and only mild toxicity was observed. After the second transplant further improvement of the response rate was obtained with 90% CR. However, we observed three toxic early infection-related deaths from CMV and legionella pneumonia at day + 17, +26, +54 after transplantation. Although this schedule seems to be effective in terms of response rate, the 30% TRM imposes an anthracycline dose-reduction with careful patient selection. This approach could reduce the toxic effects and maintain the efficacy of therapy at the same time.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cytomegalovirus Infections; Female; Humans; Idarubicin; Legionnaires' Disease; Male; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Pilot Projects; Remission Induction; Transplantation Conditioning; Transplantation, Autologous

Although the life-threatening cytomegalovirus (CMV) disease is a well known complication following allogeneic hematopoietic stem cell transplantation (HSCT), it has been considered infrequent after autologous peripheral blood stem cell transplantation (PBSCT). On the other hand, the massive involvement of the gastrointestinal (GI) tract as the primary site of fatal CMV disease is particularly rare after autologous PBSCT. We present the case of a woman who suffered from CMV disease after high-dose busulphan/melphalan/thiotepa (BuMelTT) and autologous PBSCT. The primary site of infection was the GI tract, which was extensively affected. During the fifth week post-transplant the patient started with epigastralgia, diarrhea, fever, GI bleeding, and thrombocytopenia, and she died on day +52. Another case of fatal CMV disease among the few patients treated with BuMelTT has been recently reported, which suggests that the immunodeficiency associated with that regimen can be as intense as that occurring after allogeneic BMT.

Topics: Antineoplastic Combined Chemotherapy Protocols; Busulfan; Cytomegalovirus Infections; Fatal Outcome; Female; Gastrointestinal Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Melphalan; Middle Aged; Thiotepa; Transplantation, Autologous

Patients who undergo splenectomy and recipients of allogeneic marrow (alloBMT) or peripheral stem cell transplantation are at increased risk of overwhelming infection from encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. As prophylaxis against these pathogens splenectomised patients are immunised and may also receive antibiotics for life. We report relapsing overwhelming sepsis caused by penicillin-resistant pneumococcus in a patient who was immunised and received prophylactic phenoxymethylpenicillin for 8 months following splenectomy and matched unrelated donor (MUD) marrow transplantation for refractory T cell lymphoma. No obvious focus of sepsis was found during any of the three episodes and S. pneumoniae serogroup 6, subtype 6B was isolated from blood cultures on each occasion. He was treated with i.v. cephalosporins, as the organisms were resistant to penicillin with a minimum inhibitory concentration (MIC) of 2.0, and there was complete resolution of symptoms each time. In the light of recurrent sepsis with this penicillin-resistant organism the decision was made to give prophylactic levofloxacin for the next 12 months. This case illustrates that the choice of prophylactic regimen and the treatment of sepsis in immunocompromised patients remain difficult and challenging issues.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Bone Marrow Transplantation; Carmustine; Cefotaxime; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Cytomegalovirus Infections; Doxorubicin; Drug Therapy, Combination; Etoposide; Humans; Idarubicin; Immunocompromised Host; Immunosuppressive Agents; Levofloxacin; Lymphoma, T-Cell; Male; Melphalan; Ofloxacin; Penicillin Resistance; Pneumococcal Infections; Prednisone; Recurrence; Rifampin; Splenectomy; Streptococcus pneumoniae; Transplantation Conditioning; Vincristine

Topics: Adult; Animals; Antibodies, Monoclonal; Bone Marrow Transplantation; Cyclophosphamide; Cytomegalovirus Infections; Graft vs Host Disease; Humans; Immunoglobulin G; Immunosuppression Therapy; Melphalan; Mice; Pilot Projects; Receptors, Interleukin-2; Transplantation, Homologous; Whole-Body Irradiation

A patient with multiple myeloma had pancytopenia after treatment with melphalan and prednisone and died of an interstitial pneumonia. Post-mortem examinations showed cytomegalic cells in the lungs. Lung tissue showed a high titer of cytomegalovirus. Only when other causes have been ruled out by microbiologic, serologic, and histologic examinations should melphalan be believed to cause respiratory illness.

Topics: Cytomegalovirus Infections; Humans; Lung; Male; Melphalan; Middle Aged; Multiple Myeloma; Pneumonia, Viral; Prednisone