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Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m(2); n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT.

This study aimed to evaluate the efficacy of a nonmyeloablative conditioning consisting of fludarabine and TBI in patients aged > or =60 years.A total of 32 patients (median age 62 years; range 60-70) with hematological malignancies were treated with fludarabine (30 mg/m(2) x 3-5 days) and 200 cCy TBI followed by allogeneic hematopoietic stem cell transplantation (HSCT) from a matched-sibling donor. GVHD prophylaxis consisted of cyclosporine and mycophenolate. Neutrophil recovery occurred in all patients at a median time of 16 days (range 9-34). Six patients did not become granulocytopenic. On day +30, 10 patients had >95% donor chimerism and 19 patients had mixed chimerism. The cumulative probabilities of Grade II-IV acute GVHD and chronic GVHD were 48 and 83%, respectively. Transplant-related mortality at 100 days and 1 year was 6 and 10%, respectively. The probabilities of 2-year overall (OS) and progression-free survival (PFS) were 39 and 35%, respectively. The estimated 2-year probability of OS and PFS for patients in early disease stages were 77 and 64%, respectively, which were significantly higher than the survival and PFS estimates of 0% obtained in patients with advanced disease stages at the time of transplant. Our analysis would suggest that for patients older than 60, this regimen is well tolerated and associated with a low incidence of transplant-related mortality. The leukemic burden at time of transplant has proven to be the most important risk factor for the outcome.

A new HLA-DRB5 allele, HLA-DRB5*0113, has been identified in an Italian patient during routine HLA typing in order to activate a bone marrow donor search. HLA typing was performed by different molecular biology techniques, and the results showed that the HLA-DRB5*0113 allele differs from HLA-DRB5*010101 allele for three nucleotide substitutions at codons 57 (GAC-->GAT; Asp) and 58 (GCT-->GAG; Ala-->Glu) of exon 2.

PURPOSE/OBJECTIVE:The use of low-dose, irradiation-based preparative regimens have allowed the extension of allografting to older and medically infirm patients. The study reported here assessed outcomes for patients with acute myeloid leukemia (AML) in different stages of their disease, who were not considered candidates for conventional hematopoietic cell transplantation (HCT) because of age and/or other known risk factors and were given minimal conditioning followed by HCT from related or unrelated donors. PATIENTS AND METHODS/METHODS:The present study included 122 patients with AML, who were conditioned with 2 Gy total-body irradiation (TBI) on day 0 with or without preceding fludarabine (30 mg/m2/d from days -4 to -2), and given postgrafting cyclosporine at 6.25 mg/kg twice daily from day -3 and mycophenolate mofetil at 15 mg/kg twice daily from day 0. RESULTS:Durable engraftment was observed in 95% of the patients. Cumulative incidences of acute graft-versus-host disease grades 2 to 4 at 6 months were 35% after related and 42% after unrelated HCT, respectively. With a median follow-up of 44 months (range, 26 to 79 months), 51 patients were alive, of whom 48 were in complete remission (CR). Cumulative nonrelapse mortalities were 10% and 22%, and cumulative mortalities from disease progression were 47% and 33% at 2 years for related and unrelated recipients, respectively. Overall, 2-year survival was 48%, and disease-free survival was 44%. Patients receiving transplantation in CR1 had 2-year overall survivals of 44% after related and 63% after unrelated HCT, respectively. CONCLUSION/CONCLUSIONS:We conclude that HCT from related and unrelated donors after low-dose TBI is a promising treatment for elderly patients with AML.

OBJECTIVES/OBJECTIVE:Thalidomide combined with conventional chemotherapies including oral melphalan shows significant anti-myeloma activity. To address this issue, feasibility and efficacy of a three drug combination consisting of intravenous (i.v.) melphalan, thalidomide and prednisone [M(i.v.)PT] was evaluated in advanced myeloma patients. PATIENTS AND METHODS/METHODS:Twenty-four advanced myeloma patients were treated with multiple cycles of a regimen consisting of low dose i.v. melphalan (20 mg/m2) at d 1, thalidomide at the dose of 50-100 mg/d given continuously and oral prednisone at the planned dose of 50 mg/d every other day. Intravenous melphalan was administered every fourth month. Median time from diagnosis was 40 months (range: 8-144 months). Fifteen patients (66%) had previously been treated with a combination of thalidomide and dexamethasone or with thalidomide alone. RESULTS:Overall, on an intent-to treat basis, 14 patients responded: three achieved near complete remission (nCR), seven achieved partial response (PR), four minimal response (MR). Six patients showed stable disease (SD) and four-disease progression. Interestingly, of five patients who had previously progressed while on thalidomide and prednisone, one reached nCR, two PR and one MR. After a median follow up of 14 months, median progression free survival was 9 months. Response duration was longer than that induced by the previous line of treatment in eight patients (33%). Thalidomide-associated toxicity mainly consisted of constipation, tingling and sedation. CONCLUSIONS:M(i.v.)PT is an effective regimen, which can overcome resistance to thalidomide plus prednisone in advanced myeloma with acceptable toxicity.

Human herpesvirus 8 (HHV-8) is causally associated with Kaposi's sarcoma (KS). KS is most frequently observed in HIV patients and in solid organ transplant recipients. The role of HHV-8 in allogeneic haematopoietic cell transplantation (HCT) remains to be determined. Here we describe a case in which KS concomitantly occurred with CMV reactivation after a non-myeloablative allogeneic HCT and presented with skin lesions, but not visceral involvement. Skin biopsy confirmed the diagnosis and ruled out graft versus host disease or disease recurrence. Molecular findings indicated viral reactivation of the recipient's primary infection. Tumour lesions completely receded when immunosuppression was tapered. Prevalence studies in donors and recipients are needed to determine the clinical impact of HHV-8 in HCT.

We previously reported results in 71 patients with advanced hematologic malignancies given HLA-matched unrelated granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) grafts after fludarabine 90 mg/m(2), 2 Gy of total body irradiation, and postgrafting mycophenolate mofetil (MMF) 15 mg/kg twice daily and cyclosporine 6.25 mg/kg twice daily orally. Graft rejection was 15%; the cumulative probability of acute graft-versus-host disease (GVHD) was 52%. According to MMF pharmacokinetic studies, which showed a short half-life of its active metabolite, mycophenolic acid, we increased MMF dosing from 15 mg/kg twice daily to 15 mg/kg 3 times daily to increase immunosuppression and reduce the incidence of both graft rejection and acute GVHD. Among 103 patients so treated, graft rejection occurred in 5%, whereas acute GVHD remained at 53%. Outcomes were compared with results of previous G-PBMC recipients given MMF twice daily. Infection rates were slightly higher with MMF 3 times daily than with MMF twice daily. Nevertheless, 2-year nonrelapse mortality and overall and progression-free survivals were similar for MMF 3-times-daily and twice-daily patients (19%, 58%, and 49% versus 20%, 48%, and 37%, respectively). Nonmyeloablative conditioning with postgrafting cyclosporine and MMF given 3 times daily allowed 95% durable engraftment of unrelated donor G-PBMC grafts.

BACKGROUND:It is unknown whether the duration of systemic immunosuppressive treatment after allogeneic nonmyeloablative hematopoietic cell transplantation (HCT) might influence the incidence, severity, timing, and/or corticosteroid-responsiveness of graft-versus-host disease (GVHD). METHODS:We retrospectively analyzed outcomes among 185 patients with hematologic malignancies who were given grafts from HLA-matched related donors following conditioning with 2 Gy total body irradiation alone or in combination with fludarabine between December 1998 and March 2003. Postgrafting immunosuppression consisted of mycophenolate mofetil (days 0-27) in combination with 3 different cyclosporine (CSP) regimens: taper from (A) days 35 to 56 (n=107), (B) days 56 to 77 (n=35), and (C) days 56 to 180 (n=43). RESULTS:The overall incidences of grades II-IV and III-IV acute GVHD, and extensive chronic GVHD were 52%, 13%, and 56%, respectively. The duration of CSP prophylaxis did not significantly influence the overall rate of acute GVHD (grade II-IV), extensive chronic GVHD, or non-relapse mortality. However, prolonged administration of CSP (group C) was associated with a significantly decreased hazard of grades III-IV acute GVHD (HR 0.2, 95% CI [0.04, 0.9]) and with an increased likelihood of discontinuing all systemic immunosuppression (HR 2.4, 95% CI [1.1, 5.2]) when compared to the shortest course of CSP (group A). CONCLUSION/CONCLUSIONS:Longer CSP duration decreased the risk of severe GVHD and increased the likelihood of discontinuing all systemic immunosuppression after nonmyeloablative HCT with HLA-matched related grafts.