Dose-intense paclitaxel, etoposide and cyclophosphamide: a safe and active regimen for tumor cytoreduction and stem cell mobilization in metastatic breast cancer.

Patients with metastatic breast cancer in complete remission are the ones most likely to have an improved outcome with subsequent high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDC-PBSCT). Peripheral blood stem cells are usually procured following mobilization with single agent chemotherapy and colony-stimulating factor support. We utilized a dose-intense regimen of paclitaxel 200 mg/m2 i.v., etoposide 60 mg/kg i.v., and cyclophosphamide 3 g/m2 i.v. (TEC) followed by daily administration of granulocyte colony-stimulating factor. The aim was not only to mobilize stem cells but also to achieve optimal tumor cytoreduction prior to HDC/PBSCT. One hundred consecutive patients with metastatic breast cancer received 257 cycles of TEC between March 1994 and June 1997, with the aim of collecting 5 x 106 CD34-positive cells/kg usually following the second cycle of chemotherapy. Patient characteristics included a median age of 45 years, a median of two organ systems involved by disease, a median of two prior chemotherapy regimens and eight prior chemotherapy cycles, and a median interval of 8 months from diagnosis of metastases to first cycle of TEC. There were 61 febrile episodes during neutropenia and 13 of these were associated with bacteremia or fungemia. Mortality rate was 1%. An adequate number of stem cells was collected in 90% of patients. The overall response rate of the tumor was 58.8% with 23.7% complete responders among 97 evaluable patients. Multivariate analysis demonstrated chemosensitivity to the most recent standard chemotherapy regimen administered for metastatic disease, an ECOG performance score of 0 as opposed to 1, 2 or 3, and involvement by disease of only one organ system as significant variables for achieving a complete remission with TEC. This novel dose-intense regimen was safe and well tolerated, highly active against metastatic breast cancer, and capable of excellent stem cell mobilization. Bone Marrow Transplantation (2000) 25, 123-130.

Incidence and outcome of Clostridium difficile infection following autologous peripheral blood stem cell transplantation.

A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence and outcome of infection with Clostridium difficile. The diagnosis was confirmed in 14 patients with diarrhea (15 episodes) at a median of 33 days after stem cell infusion. Five patients were neutropenic at the time of diagnosis. Every individual had adverse known risk factors such as recent or current use of antibiotic, corticosteroid and antiviral therapy, recent administration of myeloablative chemotherapy and numerous, prolonged periods of hospitalization. Diarrhea, frequently hemorrhagic, was the most common presenting feature along with fever, abdominal cramps and abdominal distention. Diagnosis was established by the stool-cytotoxin test. Response to standard treatment with oral vancomycin or metronidazole was prompt despite the presence of several adverse prognostic features in these patients. There was only one instance of relapse which was also treated successfully. Several transplant-related variables such as age, sex, underlying malignancy, myelo-ablative regimen, duration of neutropenia, and prophylactic use of oral ampicillin underwent statistical analysis but failed to be predictive of C. difficile infection in such a setting. Finally, C. difficile is not uncommon after autologous PBSCT and must be included in the differential diagnosis in any such patient with diarrhea.

Varicella zoster virus infection associated with high-dose chemotherapy and autologous stem-cell rescue.

A retrospective evaluation of 215 consecutive recipients of high-dose chemotherapy (HDC) and autologous stem cell rescue (ASCR) was conducted to ascertain the incidence, temporal course, and outcome of varicella zoster virus (VZV) infection. Herpes zoster was identified in 40 individuals at a median of 69 days following ASCR. Six of these cases occurred at a median of 33 days prior to ASCR but following the initiation of high doses of stem cell mobilization chemotherapy. Twenty-five percent of patients demonstrated cutaneous or systemic dissemination and 32.5% required medical intervention for post-herpetic neuralgia. All except two individuals received antiviral chemotherapy. One patient with active VZV infection died of multiorgan failure 39 days after ASCR. Multivariate analysis of risk factors disclosed the significance of prophylactic acyclovir use in Herpes simplex virus seropositive individuals in reducing the risk of VZV infection. Moreover, the use of busulfan, thiotepa and carboplatin as the conditioning chemotherapy regimen was associated with an increased risk of subsequent VZV infection. The incidence of VZV reactivation after HDC and ASCR is similar to that observed following bone marrow transplantation but has an earlier onset. This may be related to an earlier induction of immunosuppression by stem cell mobilization chemotherapy administered prior to ASCR. We demonstrated a marked reduction in the proliferative and synthetic capacities of peripheral blood mononuclear cells obtained prior to and following stem cell mobilizing chemotherapy. Moreover, greater than 80% of VZV infections occurred within 6 months following ASCR and late cases were seldom observed compared to allogeneic and autologous bone marrow transplantation. The role of antiviral chemoprophylaxis during the period of maximum immunocompromise needs to be studied further in the HDC-ASCR setting.

Interferon alpha for the treatment of chronic hepatitis C in patients infected with human immunodeficiency virus. Hepatitis-HIV Spanish Study Group.

Liver disease secondary to hepatitis C virus (HCV) infection is a rising cause of morbidity and mortality among individuals who have been infected parenterally with human immunodeficiency virus (HIV) such as injection drug users, hemophiliacs, and transfused patients. We analyzed both the efficacy of interferon (IFN) alpha therapy in these patients and the predictors of response to this agent. A total of 119 patients with chronic hepatitis C (90 of whom were infected with HIV and 29 of whom were not) were included in a multicenter, prospective, open, nonrandomized observational study. IFN-alpha was given subcutaneously in a dosage of 5 million units three times a week during a 3-month period; those patients who responded received a dose of 3 million units given subcutaneously three times a week for an additional 9 months. One hundred seven patients completed the study; the level of aminotransferases returned to normal and sera became negative (complete response) for HCV RNA in 26 (32.5%) of 80 HIV-infected patients and 10 (37.0%) of 27 non-HIV-infected patients (P = .666) after completion of the treatment. Two variables were independently associated with a response in HIV-infected patients: a CD4+ T lymphocyte count of > 500 x 10(6)/L and a baseline HCV viremia level of < 10(7) copies/mL. In the 12 months following treatment, relapses occurred in 30.8% of the HIV-infected patients and 12.5% of non-HIV-infected patients (P = .403).

[The treatment of chronic hepatitis C with interferon in patients infected with the human immunodeficiency virus. The Spanish Group for the Study of Viral Hepatitis in HIV+ Patients]. / Tratamiento de la hepatitis crónica C con interferón en pacientes infectados por el virus de la immunodeficiencia humana. Grupo Español para el Estudio de las Hepatitis Víricas en Pacientes VIH+.

BACKGROUND: Alfa-interferon (aIFN) is widely recommended for the treatment of chronic hepatitis C (CHC). Hepatitis C virus (HCV) infection is very common in injecting drug users (IDUs), which in Spain represent the large number of HIV-infected persons. Interaction between human immunodeficiency virus (HIV) and HCV in coinfected patients might accelerate the clinical course of HCV-associated liver disease. The efficacy and safety of aIFN therapy in HIV-infected patients with CHC is not well known. PATIENTS AND METHODS: In a multicenter, prospective, open, non randomized and partially controlled study, we compared the efficacy and safety of aIFN therapy in 119 patients with CHC, of whom 90 were HIV-positive and 29 HIV-negative. Interferon was started at 5 mega U tiw for 3 months, followed in responders by 3 megaU tiw for additional 9 months. RESULTS: One hundred seven patients completed the study. A normalization of the aminotransferase values at the end of treatment (complete response, CR) was observed in 26/80 (32.5%) HIV-positive and 10/27 (37.0%) HIV-negative individuals (p = 0.666). Relapses at 12 months of stopping aIFN were seen in 30.8% of HIV-positive subjects and 12.5% of HIV-negatives (p = 0.403). Side effects were uncommon and did not have severity; only one patient required to stop the medication. However, 3 HIV-positive subjects treated with aIFN (3.5% of them) showed an irreversible fall of CD4+ T-cells below half the baseline values. CONCLUSION: HIV-infected patients with CHC seems to respond to aIFN with a similar rate than HIV-negatives. Moreover, the drug is similarly well tolerated in both groups of patients, although a fall of CD4+ T-cells is an unusual side effect of particular relevance observed in HIV-infected patients.