Posttraumatic stress disorder in breast cancer patients following autologous bone marrow transplantation or conventional cancer treatments.

We assessed 17 women who had undergone autologous bone marrow transplants (BMT) for their breast cancer and 20 other women who had been treated for breast cancer (but not with BMT) by structured clinical interviews examining each stage of the breast cancer experience (e.g. initial diagnosis, initial treatment, recurrence of cancer (if applicable) and BMT (if applicable)) and at follow-up points; 3, 6 and 12 months (if applicable) posttreatment. The two groups did not differ on incidence of posttraumatic stress disorder (PTSD), major depressive disorder (MDD) or generalized anxiety disorder at any stage. We found a high rate of PTSD over the cancer experience, 35% for the combined sample, with cancer diagnosis being the most likely point for developing PTSD, 27% for the combined sample. None of the 17 women who had undergone BMT developed PTSD as a result of the treatment.

Hydroxychloroquine for the treatment of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. Both the disease and the medications used to treat it are associated with significant morbidity and mortality. The manifestations of chronic GVHD often resemble those of autoimmune disorders. Hydroxychloroquine (HCQ) is a 4-aminoquinoline antimalarial drug used for the treatment of autoimmune diseases. HCQ interferes with antigen processing and presentation, cytokine production, and cytotoxicity and is synergistic with cyclosporine and tacrolimus in vitro. Forty patients with steroid-resistant or steroid-dependent chronic GVHD were enrolled in a phase 2 trial of HCQ 800 mg (12 mg/kg) per day. Three complete responses and 14 partial responses were seen in 32 evaluable patients (53% response rate). All responders tolerated a >50% reduction in their steroid dose while receiving HCQ. Clinical response occurred at a median of 8 weeks (range, 4 to 24 weeks). No hematologic, hepatic, renal, or retinal toxicity was associated with HCQ. In light of its mechanisms of action, clinical activity for GVHD, and low toxicity profile, HCQ may be useful in a multiagent approach for the treatment of extensive chronic GVHD.

Autotransplants in men with breast cancer. ABMTR Breast Cancer Working Committee. Autologous Blood and Marrow Transplant Registry.

The purpose of this study was to determine the outcome of high-dose therapy with autologous hematopoietic stem cell support (autotransplants) in men with breast cancer. We studied 13 men receiving autotransplants for breast cancer and reported to the Autologous Blood and Marrow Transplant Registry (ABMTR) by 10 centers. Six men had stage 2 breast cancer, four had stage 3, and three had metastatic breast cancer. Of twelve tumors tested, all were estrogen receptor positive. Median age at transplant was 50 years. The most common conditioning regimen was cyclophosphamide, thiotepa and carboplatin (n = 5); the remaining eight men received other alkylator-based regimens. Three men received bone marrow, eight received blood stem cells, and two received both for hematopoietic support. All patients had hematopoietic recovery. There were no unexpected regimen-related toxicities. Of 10 men receiving autotransplants as adjuvant therapy, three relapsed 3, 5 and 50 months post-transplant and died 16, 19 and 67 months post-transplant. Seven of 10 are disease-free with median follow-up of 23 months (range 6-50 months). Of three men treated for metastatic breast cancer, one had progressive disease and two recurrent disease at 6, 7 and 16 months post-transplant. In conclusion, results of autotransplants for male breast cancer appear similar to those reported for women receiving autotransplants for breast cancer.

The basis of informed consent for BMT patients.

During recent decades the doctrine of informed consent has become a standard part of medical care as an expression of patients' rights to self-determination. In situations when only one treatment alternative exists for a potential cure, the extent of a patient's self-determination is constrained. Our hypothesis is that for patients considering a life-saving procedure such as bone marrow transplant (BMT), informed consent has little meaning as a basis for their right to self-determination. A longitudinal study of BMT patients was undertaken with four self-administered questionnaires. Questions centered around expectations, knowledge, anxiety and factors contributing to their decision to undergo treatment. Although the informed consent process made patients more knowledgeable about the treatment, their decision to consent was largely based on positive outcome expectations and on trust in the physician. Informed consent relieved their anxieties and increased their hopes for survival. Our conclusion was that the greatest value of the informed consent process lay in meeting the patients' emotional rather than cognitive needs. When their survival is at stake and BMT represents their only option, the patient's vulnerability puts a moral responsibility on the physician to respect the principle of beneficence while not sacrificing the patient's right to self-determination.

Peripheral blood stem cells: a historical perspective.

Peripheral blood stem cells (PBSC) are rapidly becoming the primary rescue modality for autologous transplantation and are now actively being investigated in the allogeneic transplant setting. Many investigators and clinical researchers believe that PBSC are likely to replace bone marrow stem cells entirely, for use in clinical transplantation in the not too distant future (1). In order to better understand the rapidly changing developments in this field, it would be helpful to understand the historical development of this technology. The purpose of this article is to build for the reader a strong historical foundation with the intent to integrate the history of peripheral blood stem cells with their subsequent isolation, mobilization, collection, and clinical applications.

Phase I-II trial of high-dose cyclophosphamide, carboplatin and autologous bone marrow or peripheral blood stem cell rescue.

In an effort to evaluate the toxicities and anti-tumor efficacy of the combination of high-dose cyclophosphamide (CY) and carboplatin, we undertook a phase I-II trial with autologous bone marrow (BM) or peripheral blood stem cell (PBSC) rescue for patients with solid tumors. Forty three patients, 39 of whom had either high risk stage II or III or metastatic breast cancer were treated with escalating doses of carboplatin 1200-1800 mg/m2 and cyclophosphamide 4800-6000 mg/m2 over 3 days followed by autologous BM or PBSC infusion. No life-threatening or fatal toxicities were observed. Reversible congestive heart failure was seen in two patients. Transient hepatotoxicity, characterized primarily by elevation of transaminase levels, and nausea and vomiting, adequately managed with anti-emetic therapy, were seen in 39 and 40 of 43 patients, respectively. The 14 month post-transplant probability of relapse-free survival for 26 patients with high risk II-III breast cancer was 79%; for 13 patients with metastatic disease, the 22 month relapse-free survival probability was 23%. High-dose carboplatin and CY at maximally administered doses of 1800 mg/m2 and 6000 mg/m2 is a well tolerated preparative transplant regimen for autologous BM or PBSC transplantation. It appears to have similar anti-tumor activity and an improved safety profile when compared with other commonly employed transplant preparative regimens.

Randomized double-blind, placebo-controlled evaluation of oral ondansetron in the prevention of nausea and vomiting associated with fractionated total-body irradiation.

PURPOSE: To evaluate oral ondansetron in the prevention of total-body irradiation (TBI)-induced nausea and vomiting. METHODS: Twenty patients who received 4 days of TBI as part of their preparative regimen before bone marrow transplantation were randomized to receive either 8-mg oral doses of ondansetron or placebo. Administration of drug was double-blinded. Initial rescue therapy consisted of intravenous (i.v.) ondansetron 0.15 mg/kg following two or more emetic episodes between successive fractions of TBI or five total emetic episodes during the 4 days of therapy. If, after receipt of i.v. ondansetron, patients had two or more emetic episodes between fractions of TBI or five total emetic episodes, additional antiemetics were administered. RESULTS: Patients who received oral ondansetron had significantly fewer emetic episodes compared with those who received placebo (P = .005) over the entire 4-day study period. Oral ondansetron was also significantly superior to placebo with respect to the time of onset of emesis or rescue (P = .003). Six of 10 patients treated with oral ondansetron completed the study without additional antiemetic therapy, while none of 10 patients who received placebo completed the study without rescue antiemetic therapy. Six placebo patients who received initial rescue therapy with i.v. ondansetron required no additional antiemetics. No relationships were apparent between peak ondansetron concentration (Cmax) or area under the concentration versus time curve (AUC) and number of emetic episodes. CONCLUSION: Oral ondansetron is an effective therapy for the prevention of emesis induced by TBI.

The impact of harvest center on quality of marrows collected from unrelated donors.

The total number and distribution of nucleated cells in harvested bone marrow are potentially important determinants of patient outcome following bone marrow transplantation. In order to assess whether marrows collected from predominantly unrelated donors at Georgetown University Medical Center (GUMC) were different in cellular content from marrows collected at harvest centers outside of GUMC, we compared the nucleated cell counts and mononuclear cell subset distribution (CD34, CD3, CD4, CD8, CD19 antigen-positive cell content) of 10 consecutive marrows harvested at GUMC to 10 unrelated donor marrows from outside harvest centers. Significantly higher nucleated cell counts and CD34 antigen-positive cell content and significantly lower CD3 and CD4 antigen-positive T-cell numbers were demonstrated among the marrows harvested at GUMC. These results confirmed significant variability in marrow collection practices between GUMC and 10 different outside harvest centers and suggest that strict adherence to a specific collection procedure, involving small volume marrow aspirations and multiple puncture sites, results in a product with a high number of early hematopoietic progenitor cells and minimal contamination by peripheral blood. These data further suggest the need for careful monitoring of individual unrelated donor marrow collection centers' practices to optimize the quality of the harvested marrow.