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Background: Bone mineral density (BMD) loss commonly occurs after hematopoietic cell transplantation (HCT). Hypothesizing that genetic variants may influence post-HCT BMD loss, we conducted a prospective study to examine the associations of single nucleotide polymorphisms (SNP) in bone metabolism pathways and acute BMD loss after HCT. Methods and Findings: We genotyped 122 SNPs in 45 genes in bone metabolism pathways among 121 autologous and allogeneic HCT patients. BMD changes from pre-HCT to day +100 post-HCT were analyzed in relation to these SNPs in linear regression models. After controlling for clinical risk factors, we identified 16 SNPs associated with spinal or femoral BMD loss following HCT, three of which have been previously implicated in genome-wide association studies of bone phenotypes, including rs2075555 in COL1A1, rs9594738 in RANKL, and rs4870044 in ESR1. When multiple SNPs were considered simultaneously, they explained 5-35% of the variance in post-HCT BMD loss. There was a significant trend between the number of risk alleles and the magnitude of BMD loss, with patients carrying the most risk alleles having the greatest loss. Conclusion: Our data provide the first evidence that common genetic variants play an important role in BMD loss among HCT patients similar to age-related BMD loss in the general population. This infers that the mechanism for post-HCT bone loss is a normal aging process that is accelerated during HCT. A limitation of our study comes from its small patient population; hence future larger studies are warranted to validate our findings. [ABSTRACT FROM AUTHOR]

Thalidomide has been associated with venous thrombotic events, as reported in the post-marketing surveillance reports by Celgene Corporation; as well as case reports in the literature. Seven arterial thrombotic events have been reported in patients receiving thalidomide with 3 cases occurring in patients with other predisposing conditions. We report 4 additional cases of arterial thromboses in 1 lymphoma and 3 myeloma patients treated with thalidomide. The mechanism for these events is unclear; however, it is significant that 2 patients were receiving concomitant anticoagulation with aspirin and warfarin. [ABSTRACT FROM AUTHOR]

Seven morphologists examined 382 slide and 82 non-slide, post-Chernobyl pediatric acute leukemia (AL) cases in radiation-exposed areas of Belarus, Russia and Ukraine; part of a case-control study by the International Consortium for Research on the Health Effects of Radiation. Among the slide cases, 99% were confirmed as AL: 92% acute lymphoid leukemia (ALL) and 86% acute myeloid leukemia (AMD demonstrating the utility of FAB classification for distinguishing ALL and AML. Among the non-slide cases, 79% were confirmed as AL: 84% ALL, and 71% AML. This study affirms AL diagnostic accuracy during a time of social upheaval in the former Soviet Union. [Copyright &y& Elsevier]

Many challenges emerged during completion of a study to examine radiation dose and acute leukemia among children in areas of the former Soviet Union. In an era of globalization, our experiences might benefit others involved in multinational investigations. [ABSTRACT FROM AUTHOR]

Context: Women with breast cancer are the most frequent recipients of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (autotransplants) in North America. Despite widespread use, controversy exists about the benefits of and appropriate patients for this therapy.Objective: To determine factors associated with disease progression or death after autotransplantation in women with metastatic breast cancer.Design: Analysis of data collected retrospectively (January 1989 to 1992) and prospectively (1992 through January 1995) for the Autologous Blood and Marrow Transplant Registry.Setting: Sixty-three hospitals in North America, Brazil, and Russia.Participants: A total of 1188 consecutive women aged 18 to 70 years receiving autotransplants for metastatic or locally recurrent breast cancer, with a median follow-up of 291/2 months.Main Outcome Measure: Time to treatment failure (disease progression, disease recurrence, or death) after autotransplantation.Results: Factors associated with significantly (P<.05) increased risk of treatment failure in a Cox multivariate analysis included age older than 45 years (relative hazard, 1.17; 95% confidence interval [CI], 1.02-1.33), Karnofsky performance score less than 90% (1.27; 95% CI, 1.07-1.51), absence of hormone receptors (1.31; 95% CI, 1.15-1.51), prior use of adjuvant chemotherapy (1.31; 95% CI, 1.10-1.56), initial disease-free survival interval after adjuvant treatment of no more than 18 months (1.99; 95% CI, 1.62-2.43), metastases in the liver (1.47; 95% CI, 1.20-1.80) or central nervous system (1.56; 95% CI, 0.99-2.46 [approaches significance]) vs soft tissue, bone, or lung, 3 or more sites of metastatic disease (1.32; 95% CI, 1.13-1.54), and incomplete response vs complete response to standard-dose chemotherapy (1.65; 95% CI, 1.36-1.99). Receiving tamoxifen posttransplantation was associated with a reduced risk of treatment failure in women with hormone receptor-positive tumors (relative hazard, 0.60; 95% CI, 0.47-0.87). Women with no risk factors (n = 38) had a 3-year probability of progression-free survival of 43% (95% CI, 27%-61 %) vs 4% (95% CI, 2%-8%) for women with more than 3 risk factors (n = 343).Conclusion: These data indicate that some women are unlikely to benefit from autotransplantation and should receive this treatment only after being provided with prognostic information and in the context of clinical trials attempting to improve outcome. [ABSTRACT FROM AUTHOR]

We evaluated the results of high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with diffuse aggressive non-Hodgkin lymphoma (NHL) in first relapse (Rel 1) or second complete remission (CR 2). Data were evaluated from the Autologous Blood and Marrow Transplant Registry on 429 patients with diffuse aggressive NHL who underwent transplantation in Rel 1 or CR 2. Transplantations were performed between 1989 and 1996 and were reported to the Autologous Blood and Marrow Transplant Registry by 93 centers in North and South America. The probability of 3-year survival was 44% (95% confidence interval [CI], 33%–55%). The probability at 3 years of progression-free survival was 31% (95% CI, 27%–36%). Patients who underwent transplantation in CR 2 had a 3-year probability of progression-free survival of 38% (95% CI, 30%–46%) compared with 28% (95% CI, 22%–33%) for those who were not in remission at the time of transplantation (P < .001). In multivariate analysis, chemotherapy resistance, increased lactic dehydrogenase at diagnosis, an interval of <12 months from diagnosis to relapse, age ≥40 years, and use of myeloid growth factors to accelerate posttransplantation bone marrow recovery were adverse predictors of survival. High-dose chemotherapy and autologous hematopoietic stem cell transplantation for patients with diffuse aggressive NHL in CR 2 or Rel 1 resulted in better outcome for patients with chemotherapy-sensitive disease, longer relapse-free intervals, and age <40 years. Exposure to myeloid growth factors to accelerate recovery for recipients of bone marrow grafts may increase the risk of disease progression or death. [Copyright &y& Elsevier]

Evidence supporting the role of hematopoietic stem cell transplantation (SCT) in the therapy of multiple myeloma (MM) is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published medical literature and for grading the quality of the evidence, the strength of the evidence, and the strength of the treatment recommendations. Treatment recommendations based on the evidence presented in the review were made unanimously by a panel of MM experts. Recommendations for SCT as an effective therapy for MM include the following: SCT is preferred to standard chemotherapy as de novo therapy; SCT is preferred as de novo rather than salvage therapy; autologous peripheral blood stem cell transplantation (PBSCT) is preferred to bone marrow transplantation (BMT); and melphalan is preferred to melphalan plus total body irradiation as the conditioning regimen for autologous SCT. Recommendations that SCT is not effective include the following: current purging techniques of bone marrow. Recommendations of equivalence include the following: PBSCT using CD34+ selected or unselected stem cells. No recommendation is made for indications or transplantation techniques that have not been adequately studied, including the following: SCT versus standard chemotherapy as salvage therapy, tandem autologous SCT, autologous or allogeneic SCT as a high-dose sequential regimen, allogeneic BMT versus PBSCT, a preferred allogeneic myeloablative or non-myeloablative conditioning regimen, and maintenance therapy post–autologous SCT with interferon alpha post-SCT. The priority area of needed future research is maintenance therapy posttransplantation with nothing versus interferon alpha versus other agents such as corticosteroids or thalidomide or its derivatives. © 2003 American Society for Blood and Marrow TransplantationBiology of Blood and Marrow Transplantation 9:4-37 (2003) [Copyright &y& Elsevier]