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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.

Summary: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. Keywords: informed consent; understanding; trust; beneficence; patient autonomy A patient undergoing a very complex and potentially lifesaving procedure such as a bone marrow transplant (BMT) is required to make difficult decisions based on extensive and complicated information. The difficulties of the decision-making process are exacerbated by the emotionally and physically demanding circumstances surrounding a potentially terminal illness. By virtue of having a particular life-threatening illness, patients are, so to speak, 'forced' to consider BMT if they are to have a chance to survive in the long term. In such situations, their voluntariness to consent is constrained.The notion of constrained voluntariness and its impliCorrespondence: LH Jacoby,

Compana and Pui' have failed to mention in their well-balanced and lucid review article on minimal residual disease (MRD) in leukemia two important practical aspects of quantitating MRD by polymerase chain reaction (PCR). First, the quantitation of MRD by PCR is not precise, and the method based on Poisson statistics used by Brisco et aI2 is no exception. If MRD quantitation were to be performed on the same sample on different days, up to twofold difference in the amount of MRD may be observed. This poor reproducibility should be kept in mind before changing treatment based on the detection of MRD. Second, the method of preparation of the remission bone marrow for DNA extraction may also influence the amount of MRD detected. For example, the PCR method is likely to amplify target genes from DNA released from dead cells (not clonogenic). The time taken for the bone marrow to remove the dead leukemic cells may be variable depending on the initial leukemic load and the ability of the reticuloendothelial system to remove the debris. DNA prepared from a buffy coat preparation or a whole bone marrow suspension is more likely to contain DNA from dead cells as opposed to DNA prepared from, eg, Hypaque-Ficoll-separated bone marrow cells. These two practical issues may explain the wide variations in the reported percentage of patients with MRD at the time of initial remission (around 6 weeks from diagnosis) and might partly explain the observation that the percentage of patients with detectable MRD is lower in studies reporting MRD after several months from diagnosis.' These practical issues must be addressed in prospective studies designed to validate the prognostic importance of MRD in acute leukemia. It is premature to intensify therapy in patients with a high amount of MRD at the time of initial remission and to decrease therapy in patients with no detectable MRD. It must be kept in mind that prognosis in leukemia is relative to the txeatment and that good results obtained in patients with no MRD may be because of the currently available therapy, which is better than the therapy used 2 decades ago. To change the current practice in good prognosis patients may be an invitation for disaster.

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.