Lipid formulations of amphotericin B preserve and stabilize renal function in HSCT recipients.

The current study assessed renal function based on medical records in adult hematopoietic stem cell transplant (HSCT) recipients with proven or probable invasive fungal infection (IFI) transplanted between 1995 and 2000. We confirm that amphotericin B deoxycholate (AmB-d) is nephrotoxic in a large percentage of HSCT recipients. Due to nephrotoxicity, defined as serum creatinine (SCr) >2.5 mg/dl or a 100% increase in SCr from baseline, 88% of patients treated with AmB-d were switched to a lipid formulation of amphotericin B (LFAB). In total, 53% of patients initiated on AmB-d were switched within the first week of therapy. Significantly more patients (70.6%) treated with AmB-d experienced a 100% increase in SCr from baseline compared to patients treated with either AmBisome (44.4%) or Abelcet (41.2%). A Cox Proportional Hazards Model revealed that, compared to patients initiated on AmBisome or Abelcet, the risk of nephrotoxicity (RR=1.5 vs AmBisome; RR=1.7 vs Abelcet), dialysis (RR=2.4 vs AmBisome; RR=1.4 vs Abelcet), and death (RR=2.0 vs AmBisome; RR=1.1 vs Abelcet) were all increased for patients initiated on AmB-d. Study results suggest that renal function improves and mortality declines when an LFAB is given to HSCT patients as initial therapy rather than as second-line therapy, the current practice.

Predictive value of left ventricular ejection fraction in stem cell transplantation.

We evaluated predictive value of left ventricular ejection fraction at rest (REF) and its increment with exercise (deltaEF) on autologous and allogeneic stem cell transplantation mortality. In a 7 year period, a total of 163 patients evaluated for stem cell transplantation were studied. All were followed for at least 3 months after the transplant. REF was discriminatory for peritransplant mortality only in younger (<43 years) patients (n = 66), particularly those who underwent autologous transplantation (n = 30). Resting ejection fraction was not a discriminator for early death in any other subgroup. Cardiac reserve (deltaEF) was significantly lower in patients (n = 35), who died early. The finding was most prominent in younger patients who underwent autologous transplantation (n = 26). Combination of decreased REF and low deltaEF (n = 18) was associated with high peritransplant mortality (56%), after both autologous and allogeneic transplantation. A low REF with an appropriate deltaEF (n = 43) was associated with a 19% peritransplant mortality and no deaths in the autologous group. These observations indicate that resting ejection fraction is of only limited value for pretransplant evaluation. However, measurement of cardiac reserve during exercise can provide important prognostic information before stem cell transplantation.

Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols.

The PVSG was organized in 1967 to establish effective diagnostic criteria for polycythemia vera, to study the natural history of the disease and to define the optimal treatment. Although polycythemia vera and the other myeloproliferative diseases are relatively uncommon, the PVSG was able to accumulate well over 1,000 patients with these various disorders and to study them according to a total of 15 different protocols. PVSG-01, a long-term randomized controlled study of phlebotomy alone compared with the myelosuppressive agents, 32P or chlorambucil supplemented by phlebotomy, continues to receive follow-up data on 93% of surviving patients 18 years after initiation of the study. During its lifetime, PVSG has developed a widely accepted and highly effective set of criteria for the specific diagnosis of polycythemia vera as well as useful criteria for the diagnosis of essential thrombocythemia. It has gathered an enormous volume of data on the natural history of the myeloproliferative diseases and in particular on the nature of the prevalent complications, such as thrombotic events and hematologic and nonhematologic malignancies. With respect to the final question, the optimal treatment for polycythemia vera, it is apparent that the expectation of a single optimal therapy that would apply to all patients at all ages and stages of the disease was naive. Nevertheless considerable progress has been made. Moreover, the group has defined more precisely than ever before the nature of the complications of the disease and the association of the risks of specific complications with specific forms of therapy. It thus has made it possible to pose the next series of therapeutic questions that must be addressed in this disorder with a greater degree of sophistication than was previously possible.

Therapeutic implications of collagen metabolism in myelofibrosis.

Myelofibrosis is an idiopathic condition of man associated with increased deposition of bone marrow collagen. This is directly seen on bone marrow reticulin or collagen staining, and reflected by increased levels of serum procollagen III aminoterminal peptide (28). It is but one of a number of diseases in which collagen, and an aberration of the connective tissue matrix, influence normal anatomy and physiology. Animal experiments have shown that the therapeutic manipulation of the intra- and extracellular processing of collagen with various agents can influence its deposition and the degree of end-organ damage. Several of these drugs have been used therapeutically for various clinical conditions and deserve clinical trials to evaluate their effectiveness in myelofibrosis. Bone marrow fibrosis, and peripheral serum markers which reflect collagen metabolism could be followed as experimental parameters. Development of an effective and safe antifibroblastic therapy is awaited eagerly. An attempt to prevent the fibrosis found in myelofibrosis, as opposed to managing its complications, would revolutinize our approach to managing these patients.

Adult respiratory distress syndrome as a cause of death in pneumococcal pneumonia. Report of ten cases.

The Pneumococcus continues to be a common cause of infectious pneumonia; however, the cause of death in pneumococcal disease remains obscure. Ten patients are described who developed the adult respiratory distress syndrome (ARDS) secondary to pneumococcal pneumonia. The patients are young (median age, 33 years) and leukopenic (median white blood cell count, 2.1 cells/cu mm) and have a mortality of 50 percent (five patients). It is postulated that pulmonary sequestration of leukocytes may play a role in the pathogenesis of ARDS secondary to pneumococcal disease. Four different pneumococcal capsular subtypes (9V [68]; 9A [33]; 4; 3) were found capable of causing ARDS. The currently available pneumococcal vaccine does not contain two of the capsular subtypes associated with ARDS.