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Several studies have shown that a higher lymphocyte count 3-4 weeks after allogeneic stem cell transplantation (SCT) is associated with better transplant outcome. However, the factors determining early lymphocyte recovery are not defined. To further explore the relationship between lymphocyte recovery and outcome we analyzed lymphocyte counts and other engraftment parameters in 157 patients with leukemia (48 acute myelogenous leukemia, 80 chronic myelogenous leukemia, and 29 acute lymphoblastic leukemia [ALL]) receiving T cell-depleted myeloablative SCT from an HLA-identical sibling. In multivariate analysis the day 30 absolute lymphocyte count (LC30) above the median of 450/muL was associated with improved survival (71% +/- 5% versus 38% +/- 6%, P < .0001), less relapse (21% +/- 5% versus 44% +/- 7%, P = .009), less nonrelapse mortality (NRM; 9 +/- 3 versus 36% +/- 6%, P < .0001) and less acute graft-versus-host disease (aGVHD) (34% +/- 5% versus 51% +/- 6%, P = .025). The beneficial effect of a higher LC30 influenced outcome in patients with both standard and high-risk disease but did not affect survival and relapse in ALL. We found that a higher LC30 correlated with higher lymphocyte counts at all time points between 30 and 90 days post-SCT and also with more rapid neutrophil and platelet engraftment. These results indicate that LC30 is a surrogate for robust engraftment and identifies an "at-risk" population of patients after T cell-depleted SCT.

Basic fibroblast growth factor (FGF-2), an important modulator of cartilage and bone growth and differentiation, is expressed and regulated in osteoblastic cells. To investigate the role of FGF-2 in bone, we examined mice with a disruption of the Fgf2 gene. Measurement of trabecular bone architecture of the femoral metaphysis of Fgf2(+/+) and Fgf2(-/-) adult mice by micro-CT revealed that the platelike trabecular structures were markedly reduced and many of the connecting rods of trabecular bone were lost in the Fgf2(-/-) mice. Dynamic histomorphometry confirmed a significant decrease in trabecular bone volume, mineral apposition, and bone formation rates. In addition, there was a profound decreased mineralization of bone marrow stromal cultures from Fgf2(-/-) mice. This study provides strong evidence that FGF-2 helps determine bone mass as well as bone formation.

Pulmonary function (PF) was studied in 69 consecutive patients with hematologic diseases, with a minimum 5-year (range, 5-13 years) follow-up after allogeneic stem cell transplantation from an HLA-matched sibling. Fifty-six patients (81%) received total body irradiation based myeloablative stem cell transplantation (MT) and 13 (19%) underwent nonmyeloablative stem cell transplantation (NST). Thirty-one patients (45%) developed a late decrease in PF from baseline, 25 with a restrictive and 6 with an obstructive pattern PF abnormality. Twelve patients (17%) were symptomatic, 8 with a severe restrictive PF defect, but none required supplemental oxygen. The incidence of developing a late PF abnormality was comparable in MT (24 of 56) and NST (5 of 13; P = .51). In multivariate analysis, chronic graft-versus-host disease (relative risk, 16) and pretransplantation diffusion capacity for carbon monoxide or forced expiratory volume in the first second

Between July 1997 and August 2004, 146 consecutive patients with hematologic malignancies received a T cell-depleted peripheral blood stem cell transplant from an HLA-identical sibling by using total body irradiation (TBI) and cyclophosphamide conditioning regimens. Eighty-five patients received 13.6 Gy of TBI with no lung shielding, and 61 received lung shielding (total lung dose, 6–12 Gy). Ninety-four patients (65.5%) had standard-risk disease; the remainder had more advanced disease or unfavorable diagnoses. Of the 21 transplant-related deaths, 14 were from pulmonary causes (10 idiopathic pulmonary syndromes and 4 from infection) that occurred at a median of 90 days (range, 23–238 days) after transplantation. Independent risk factors for pulmonary transplant-related mortality (PTRM) were pretransplantation diffusion capacity for carbon monoxide (relative risk, 5.7 for diffusion capacity for carbon monoxide