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Over a 3-year period, 145 patients ineligible for myeloablative conditioning underwent reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (SCT) from an HLA-identical sibling in a prospective study. The median age was 54 years, 88 patients were male and 61 patients were beyond the early-intermediate phase of their disease. The 100-day probability of developing grade II-IV acute graft-versus-host disease (GVHD) was 34%, and the 1-year probability of developing chronic extensive GVHD was 41%. The 1-year probabilities of transplant-related mortality (TRM), overall (OS) and progression-free survival were 20, 60 and 52%, respectively. Multivariate analyses found a better OS in: (i) patients <60 years; and (ii) recipients of a first SCT; and a higher TRM in: (i) age >60 years, (ii) recipients of a prior autologous SCT, and (iii) an ECOG performance status >1. The 1-year TRM in patients with 0 or 1 and >2 of the above-mentioned adverse prognostic factors were 17 vs 53%, respectively (P<0.001). In summary, our study shows that elderly patients have a higher TRM following an RIC protocol. However, age by itself should not preclude these RIC transplants, since TRM appears to be unacceptably high only in the presence of additional adverse factors.

In previous studies, the prognostic value of bone marrow (BM) histologic patterns in chronic lymphocytic leukemia (CLL) has been demonstrated. In order to investigate whether such a value is independent of other prognostic parameters, a multivariate survival analysis (Cox's regression model) was undertaken in a series of 329 CLL patients in whom a BM had been performed. The following binary variables were included in the analysis: age (more than 60 years), lymphadenopathy (more than two areas involved), splenomegaly, hepatomegaly, absolute lymphocyte count (more than 30,000 microL), anemia (hemoglobin less than 10 g/dL), thrombocytopenia (less than 100,000 microL), and BM pattern (diffuse v nondiffuse). Three variables entered the regression at significant level: BM pattern (P less than .001), anemia (P less than .001), and hepatomegaly (P = .03). The model was also tested by expressing the variables in a continuous way when possible. Again, BM pattern entered first in the regression (P less than .001), followed by the hepatomegaly (P = .002), hemoglobin level (P = .02), and lymphadenopathy (P = .04). When both the binary and the continuous models were tested separately in 227 patients with BM as initial staging procedure and in 102 patients in whom this was performed later during the course of the disease, in all instances, BM pattern entered first in the regression at a highly significant level. BM histologic pattern appears to be a better single prognostic parameter than any one of the variables employed in current clinical staging systems. A combined clinicopathologic system incorporating the BM pattern, together with the usual clinical variables, is presented.