C. Christopher Hook

Pineal parenchymal tumors. Clinical, pathologic, and therapeutic aspects.

Background. Pineal parenchymal tumors are rare; therefore, only limited clinical data regarding their behavior is available. This study was performed to provide further information regarding the pathologic features, clinical behavior, and response to therapy of these tumors.

Thalidomide treatment in myelofibrosis with myeloid metaplasia

Summary.  Myelofibrosis with myeloid metaplasia (MMM) is uniquely characterized by macroscopic bone marrow stromal changes that are believed to be both reactive and cytokine mediated. Furthermore, a prognostically detrimental increase in bone marrow angiogenesis has recently been demonstrated. These observations suggest a potential therapeutic role for agents that are inhibitory to angiogenesis as well as cytokines that are pathogenetically implicated in MMM. In a prospective study of 15 patients with MMM, thalidomide treatment, starting at a dose of 200 mg/d, resulted in increased platelet counts (12 of 15 patients), increased haemoglobin level (3 of 15), a modest decrease in spleen size (3 of 12), increased bone marrow megakaryopoiesis (5 of 9) and decreased bone marrow angiogenesis (2 of 9). Undesirable haematological effects included pericardial extramedullary haematopoiesis in one patient, marked leucocytosis in two patients and extreme thrombocytosis in three patients. The thrombocytosis occurred in both patients with post‐thrombocythaemic myeloid metaplasia (PTMM) and was also associated with higher baseline levels of circulating CD34+ cells. Previously described toxicities of thalidomide were seen in the majority of patients and dose escalation to 400 mg/d was permitted in only two patients. In contrast, toxicity‐related dose reductions to 50 mg/d did not appear to lessen drug efficacy. We conclude that thalidomide has both beneficial and potentially adverse biological activity in MMM. A lower dose of the drug might be more tolerable without compromising therapeutic value. Patients with PTMM and/or markedly increased circulating CD34+ cell counts might be susceptible to thalidomide‐induced thrombocytosis.

Absolute lymphocyte count recovery after induction chemotherapy predicts superior survival in acute myelogenous leukemia

Absolute lymphocyte count (ALC) recovery postautologous stem cell transplantation is an independent predictor for survival in acute myelogenous leukemia (AML). The role of ALC recovery after induction chemotherapy (IC) in AML is unknown. We hypothesize that ALC recovery after IC has a direct impact on survival. We have now evaluated the impact of ALC recovery after IC on overall survival (OS) and leukemia-free survival (LFS) in 103 consecutive, newly diagnosed AML patients treated with standard IC and consolidation chemotherapy (CC) from 1998 to 2002. ALC recovery was studied at days 15 (ALC-15), 21 (ALC-21), 28 (ALC-28) after IC and before the first CC (ALC-CC). Superior OS and LFS at each time point were observed with an ALC-15, ALC-21, ALC-28, and ALC-CC ⩾500 cells/μl. Patients with an ALC ⩾500 cells/μl at all time points vs those who did not have superior OS and LFS (not reached vs 13 months, P<0.0001; and not reached vs 11 months, P<0.0001, respectively). Multivariate analysis demonstrated ALC ⩾500 cells/μl at all time points to be an independent prognostic factor for survival. Our data suggest a critical role of lymphocyte (immune) recovery on survival after IC in AML.

Report of 255 clinical ethics consultations and review of the literature

OBJECTIVE To review clinical ethics consultations at a tertiary care academic medical center. METHODS We retrospectively reviewed all ethics consultations (and associated patient medical records) conducted at the Mayo Clinic in Rochester, Minn, between April 6, 1995, and December 31, 2005. RESULTS Of the 255 consultations, 101 (40%) reviewed intensive care unit care, 103 (40%) involved patients who died during hospitalization, and 174 (68%) were requested by physicians. The most common primary diagnoses of the patients involved were malignancy (18%, n=47), neurologic disease (18%, n=47), and cardiovascular disease (17%, n=43). Most cases involved multiple issues: patient competency and decision-making capacity (82%, n=208), staff member disagreement with care plans (76%, n=195), end-of-life and quality-of-life issues (60%, n=154), and goals of care and futility (54%, n=138). Withholding or withdrawing measures was the focus of 132 (52%) of the consultations. We also identified previously published reports of ethics consultations and compared the findings of those reports with ours. CONCLUSIONS Despite advances in medicine, the nature of ethical dilemmas remains relatively unchanged. Issues of communication, family conflict, and futility continue to give rise to ethical quandaries.

Low-dose, single-fraction, whole-lung radiotherapy for pulmonary hypertension associated with myelofibrosis with myeloid metaplasia

Summary. Pulmonary hypertension (PH) can complicate myelofibrosis with myeloid metaplasia (MMM), may arise in the absence of evidence for thromboembolic disease and carries a grim prognosis. Four patients with MMM and severe symptomatic PH were treated with whole‐lung external beam radiotherapy in a single fraction of 100 cGy. Within 72 h, each patient noted marked symptomatic improvement and had relief of hypoxia and reduction of oedema and/or ascites. Three of the four patients enjoyed an objective improvement in pulmonary artery systolic pressure as measured by transthoracic Doppler echocardiography. Low‐dose lung radiotherapy may be a useful palliative tool for patients with MMM complicated by PH.

Rituximab for refractory and or relapsing thrombotic thrombocytopenic purpura related to immune-mediated severe ADAMTS13-deficiency: a report of four cases and a systematic review of the literature

Thrombotic thrombocytopenic purpura (TTP) is a potentially life‐threatening disorder that in significant proportion of cases is related to the development of autoantibodies to, and resulting severe deficiency of, the ADAMTS13 protease. However, ADAMTS13 deficiency does not account for all cases. Response to plasma exchange (PE) is seen in TTP with and without ADAMTS13 deficiency and is therefore indicated for all with a clinical diagnosis of TTP, although the pathogenesis of the latter group remains to be defined. Although the majority of cases respond to PE, a significant percent are refractory or experience relapse. Rituximab is being increasingly used off‐label in this setting, but many reports do not define the pathogenesis of TTP so treated. We here report our experience with, and systematically review the published experience to date, of rituximab in management of refractory and or relapsing TTP specifically related to immune‐mediated severe ADAMTS13‐deficiency. In total, 73 patients met defined study inclusion criteria. The majority (∼95%) achieved complete remission within weeks of the first application of rituximab. The reported relapse rate was low in this patient subgroup, which carry an anticipated relapse rate of up to 60%. However, caution in interpretation of this data is needed given the relatively short median duration of follow‐up of approximately 10 months. Rituximab was generally well tolerated, with few serious adverse events reported. However, three severe infectious complications were identified, including viral reactivation in keeping with black box warnings for this agent. Furthermore, reflecting the rarity of this disorder, only a relatively small number of patients have been treated and data with regards to long‐term follow‐up are largely based on individual case reports. Prospective studies are urgently needed to define the true efficacy and long‐term safety of rituximab.

A practical approach to the differential diagnosis and evaluation of the adult patient with macrocytic anemia

The most common causes of macrocytic anemias in the adults are (1) alcoholism, (2) liver diseases, (3) hemolysis or bleeding, (4) hypothyroidism, (5) folate or vitamin B12 deficiency, (6) exposure to chemotherapy and other drugs, and (7) myelodysplasia. A carefully obtained history and examination with evaluation of a peripheral blood smear and reticulocyte count should be performed in most patients with macrocytosis. Serum vitamin B12 and folate levels, serum thyroid studies, liver function studies, and bone marrow aspirate and biopsy with cytogenetic analysis are frequently required to confirm a diagnosis suspected on the basis of the initial evaluation.

Ethical Issues in Geriatrics: A Guide for Clinicians

Because of demographic trends, it is reasonable to expect that clinicians will care for an increasing number of elderly persons with challenging medical and psychosocial problems. These problems and issues, in turn, may lead to daunting ethical dilemmas. Therefore, clinicians should be familiar with ethical dilemmas commonly encountered when caring for elderly patients. We review some of these dilemmas, including ensuring informed consent and confidentiality, determining decision-making capacity, promoting advance care planning and the use of advance directives, surrogate decision making, withdrawing and withholding interventions, using cardiopulmonary resuscitation and do-not-resuscitate orders, responding to requests for interventions, allocating health care resources, and recommending nursing home care. Ethical dilemmas may arise because of poor patient-clinician communication; therefore, we provide practical tips for effective communication. Nevertheless, even in the best circumstances, ethical dilemmas occur. We describe a case-based approach to ethical dilemmas used by the Mayo Clinic Ethics Consultation Service, which begins with a review of the medical indications, patient preferences, quality of life, and contextual features of a given case. This approach enables clinicians to identify and analyze the relevant facts of a case, define the ethical problem, and suggest a solution.

A phase II trial of pirfenidone (5-methyl-1-phenyl-2-[1H]pyridone), a novel anti-fibrosing agent, in myelofibrosis with myeloid metaplasia

The anti‐fibrotic and cytokine modulatory properties of pirfenidone suggest its usefulness in the treatment of myelofibrosis with myeloid metaplasia (MMM). In a prospective study, 28 patients with MMM were treated with oral pirfenidone. Twelve patients completed 1 year of therapy; 13 were withdrawn because of disease progression and three because of drug intolerance. Only one patient experienced a clinically relevant benefit with respect to anaemia and splenomegaly. The overall lack of clinical benefit correlated with no significant improvement in the bone marrow morphological features of the disease. We conclude that pirfenidone has no significant clinical or biological activity in MMM.

The Terri Schiavo Saga: The Making of a Tragedy and Lessons Learned

The recent case of Terri Schiavo has been an important medical, legal, and ethical controversy. However, much of the public discussion of the tragedy has been based on inaccurate information regarding the facts of the case and the actual legal and ethical issues involved. This article reviews the pertinent aspects of the case and the ethical and legal questions raised and highlights the lessons we should learn from this unique story.