Emerging drugs for the treatment of myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal haematopoietic stem cell disorders characterised by ineffective haematopoiesis and an increased risk of developing acute myeloid leukaemia. At present, the only curative option is allogeneic stem cell transplantation. However, the majority of patients are not eligible for this therapy, due to excessive treatment-related morbidity and mortality or lack of a suitable donor. As a result, the need for alternative therapies is great. Our improved understanding of the molecular pathogenesis of MDS has resulted in several new promising therapeutic agents. This review will consider the rational development of new agents based on the molecular biology of MDS.

Cases from the Osler Medical Service at Johns Hopkins University.

PRESENTING FEATURES: An 85-year-old black woman presented to the Osler Medical Service complaining of a pruritic, erythematous scaly rash that was on her right thigh and abdomen and that had been worsening over the prior 3 months. She also complained of increasing fatigue, decreased exercise tolerance, and a 5-lbs weight loss. There was no orthopnea, paroxysmal nocturnal dyspnea, fevers, chills, or night sweats. She denied recent travel and exposures to or contact with ill people. Her past medical history was unremarkable. There was no history of eczema, atopy, or dermatologic conditions. Her only medication was a baby aspirin taken daily. On physical examination, she was afebrile, her blood pressure was 110/72 mm Hg, and her pulse was 82 beats per minute with a room air oxygen saturation 98%. She was mildly obese but in no apparent distress. She had 1-cm anterior cervical lymphadenopathy bilaterally and a 1-cm left axillary lymph node. Cardiovascular and chest examination was unremarkable. Her abdomen was soft and nontender, with a faint, erythematous rash that was mildly scaly but nontender in her abdominal skin fold. Her right thigh showed a large erythematous area, approximately 15 x 20 cm, which was scaly with multiple areas of discoloration (Figure 1). There was no palpable mass. She had slight edema in her right leg. Her left thigh was normal. Neurologic examination was nonfocal. Laboratory studies were notable for a white blood cell count of 17,000 cells/microL, with a differential of 46% lymphocytes. The absolute lymphocyte count was 8000 cells/microL. Hematocrit was 28%. Platelet count was normal. A comprehensive metabolic panel was normal. A peripheral blood smear (Figure 2) showed numerous atypical lymphocytes with cerebriform nuclei. Peripheral blood flow cytometry showed the presence of a clonal population of T cells that expressed CD4 and CD5 but showed a loss of CD7. What is the diagnosis?

Cases from the Osler Medical Service at Johns Hopkins University.

PRESENTING FEATURES: A 70-year-old African American man was admitted with a history of fever, chills, and malaise of several days' duration. His past medical history was notable for end-stage renal disease requiring hemodialysis, coronary artery disease, and aortic stenosis requiring a bioprosthetic aortic valve replacement. On the day of admission, the patient was noted to have a shaking chill while undergoing dialysis through his catheter and was admitted to the hospital. He complained of pain at the catheter insertion site, shortness of breath, and dyspnea on exertion, but denied chest pain. On physical examination, the patient had a temperature of 100.4 degrees F, with a heart rate of 64 beats per minute, blood pressure of 127/72 mm Hg, and an oxygen saturation of 97% on room air. He was a mildly obese man in no apparent distress. He had shotty cervical lymphadenopathy and a right subclavian dialysis catheter in place, with erythema and pus at the entry site. His jugular venous pressure was 10 cm H(2)O. Lung examination showed bibasilar rales. Heart sounds were normal, with no rub or gallop. He had a 2/6 systolic ejection murmur best heart at the left sternal border as well as a 3/6 holosystolic murmur at the apex that radiated to his left axilla. Examination of the abdomen and extremities was unremarkable. The patient's neurological examination was unremarkable, and he was alert and oriented to person, place, and time. Laboratory studies showed an elevated white blood cell count of 16,700 cells/microL. His blood urea nitrogen level was 43 mg/dL and his serum creatinine level was 4.9 mg/dL. Multiple blood cultures grew methicillin-resistant Staphylococcus aureus. An admission, chest radiograph showed no infiltrate. An admission electrocardiogram showed normal sinus rhythm with first degree atrioventricular block, left anterior fascicular block, and left ventricular hypertrophy. shows rhythm strips from lead II electrocardiograms 5 months before admission (top), on admission (middle) and 5 days after admission (bottom). What is the diagnosis?