Among patients with newly diagnosed myeloma, survival in recipients of a hematopoietic stem-cell autograft followed by a stem-cell allograft from an HLA-identical sibling is superior to that in recipients of tandem stem-cell autografts. (ClinicalTrials.gov number, NCT00415987 [ClinicalTrials.gov].).

The inclusion of ATG resulted in a significantly lower rate of chronic GVHD after allogeneic transplantation than the rate without ATG. The survival rate was similar in the two groups, but the rate of a composite end point of chronic GVHD-free survival and relapse-free survival was higher with ATG. (Funded by the Neovii Biotech and the European Society for Blood and Marrow Transplantation; ClinicalTrials.gov number, NCT00678275.).

We previously reported that patients with fibrotic, chronic graft-versus-host disease (cGVHD) have antibodies activating the platelet-derived growth factor receptor pathway. Because this pathway can be inhibited by imatinib, we performed a pilot study including 19 patients with refractory cGVHD, given imatinib at a starting dose of 100 mg per day. All patients had active cGVHD with measurable involvement of skin or other districts and had previously failed at least 2 treatment lines. Patient median age was 29 years (range, 10-62 years), and median duration of cGvHD was 37 months (range, 4-107 months). The organs involved were skin (n ‫؍‬ 17), lung (n ‫؍‬ 11), and bowel (n ‫؍‬ 5); 15 patients had sicca syndrome. Imatinib-related, grade 3 to 4 toxicity included fluid retention, infections, and anemia. Imatinib was discontinued in 8 patients: in 3 because of toxicity and in 5 because of lack of response (n ‫؍‬ 3) or relapse of malignancy (n ‫؍‬ 2). Overall response rate at 6 months was 79%, with 7 complete remissions (CRs) and 8 partial remissions (PRs). With a median follow-up of 17 months, 16 patients are alive, 14 still in CR or PR. The 18-month probability of overall survival is 84%. This study suggests that imatinib is a promising treatment for patients with refractory fibrotic cGVHD. (Blood.

Summary. The number of long-term survivors after allogeneic bone marrow transplantation (BMT) has been increasing over the past years, and quality of life (QOL) has become an important end-point. We studied 244 patients undergoing an allogeneic BMT to identify factors and events influencing psychosocial outcome. Patients enrolled received the Psychosocial Adjustment to Illness Scale (PAIS) questionnaire assessing psychological and social adjustment to chronic illness or its sequelae. Eightytwo per cent of patients had a haematological disease. The median age was 28 years at BMT, and the median follow-up was 61 months. The median overall PAIS score for all patients was 56 (range 22±76): 25% (n 61) of patients were considered to have a good QOL (# 25 percentile score); 44% (n 108) of patients had an intermediate QOL (26± 75 percentile score) and 31% (n 75) had a poor QOL (. 75 percentile score). Factors associated with a poor QOL in multivariate analysis were: patients' age at BMT (. 25 years, P , 0´01); presence of long-term sequelae (P , 0´01); chronic graft-versus-host disease (GVHD) (P , 0´05); and a short interval from BMT (, 5 years; P , 0´05). The QOL improved with time: 12% of patients reported a good QOL within 5 years compared with 38% after this time point and, conversely, 38% reported a poor QOL within 5 years compared with 24% after this time point (P , 0´0001). Older patients had significantly poorer QOL compared with younger patients (# 25 years; P 0´01). Females had significantly poorer scores when compared with males in the sexual (P , 0´0001) and psychological domains (P 0´001). The data suggest that (i) one-third of patients undergoing allogeneic BMT report a poor QOL; (ii) factors associated with poor QOL are older age, presence of long-term sequelae, chronic GVHD and short follow-up; (iii) QOL is superior in long-term survivors; and (iv) BMT affects different aspects of life in males and females. A longitudinal study is ongoing to prove the effect of time on quality of life.

Epidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival. The cumulative incidence of PP-IFDs was 5.1% at 40 days, 6.7% at 100 days, and 8.8% at 12 months post-transplantation. Multivariate analysis identified the following variables as associated with PP-IFDs: transplant from an unrelated volunteer donor or cord blood, active acute leukemia at the time of transplantation, and an IFD before transplantation in the early phase; transplant from an unrelated volunteer donor or cord blood and grade II-IV acute graft-versus-host disease (GVHD) in the late phase; and grade II-IV acute GVHD and extensive chronic GVHD in the very late phase. The risk for PP-IFD was significantly higher when acute GVHD was followed by chronic GVHD and when acute GVHD occurred in patients undergoing transplantation with grafts from other than matched related donors. The presence of PP-IFD was an independent factor in long-term survival (hazard ratio, 2.90; 95% confidence interval, 2.32 to 3.62; P < .0001). Our findings indicate that tailored prevention strategies may be useful in subpopulations at differing levels of risk for PP-IFDs.

Newly diagnosed patients with acute graftversus-host disease (GvHD, grades I-IV; n ‫؍‬ 211) were given 6-methylprednisolone (6MPred) 2 mg/kg per day for 5 consecutive days; 150 patients (71%) tapered 6MPred on day ؉5 and were considered responders; 61 patients (29%) could not taper their steroid dose and were considered nonresponders. The cumulative incidence of transplant-related mortality (TRM) for responders and nonresponders is, respectively, 27% and 49% (P ‫؍‬ .009), and the 5-year survival is 53% and 35% (P ‫؍‬ .007). Nonresponders on day ؉5 (n ‫؍‬ 61) were randomized to receive 6MPred 5 mg/kg per day for 10 days alone (n ‫؍‬ 34) or in combination with rabbit anti-thymocyte globulin (ATG, 6.25 mg/kg in 10 days; n ‫؍‬ 27). The 2 groups were balanced for clinical and GvHD characteristics. One month after randomization, 26% had a complete response; 23%, a partial response; 33%, stable GvHD; 10%, worsened; and 8%, died. There was no significant difference in response, TRM, and survival between the non-ATG and ATG group.

No abstract

Before the introduction of new drugs, we designed a trial where treatment of newly diagnosed myeloma patients was based on the presence or absence of HLAidentical siblings. First-line treatments included a cytoreductive autograft followed by a nonmyeloablative allograft or a second melphalan-based autograft. Here, we report long-term clinical outcomes and discuss them in the light of the recent remarkable advancements in the treatment of myeloma. After a median follow-up of 7 years, median overall survival (OS) was not reached (P ‫؍‬ .001) and event-free survival (EFS) was 2.8 years (P ‫؍‬ .005) for 80 patients with HLAidentical siblings and 4.25 and 2.4 years for 82 without, respectively. Median OS was not reached (P ‫؍‬ .02) and EFS was 39 months (P ‫؍‬ .02) in the 58 patients who received a nonmyeloablative allograft whereas OS was 5.3 years and EFS 33 months in the 46 who received 2 highdose melphalan autografts. Among patients who reached complete remission in these 2 cohorts, 53% and 19% are in continuous complete remission. Among relapsed patients rescued with "new drugs," median OS from the start of salvage therapy was not reached and was 1.7 (P ‫؍‬ .01) years, respectively. Allografting conferred a long-term survival and disease-free advantage over standard autografting in this comparative study. IntroductionAutologous transplantation has been regarded as the standard of care for young myeloma patients. 1 Recently, "new drugs" such as lenalidomide and bortezomib have prolonged survival. 2,3 Allografting has been considered the only potential cure. 4 However, the high transplant-related mortality (TRM) has limited its use. 5,6 After the observation that donor engraftment could be obtained after reduced-intensity purine analogbased or nonmyeloablative low-dose total body irradiation (TBI)-based conditionings, allografting has become more feasible with acceptable toxicity. [7][8][9] Combining an autograft with a nonmyeloablative conditioning and an allograft has lowered TRM to approximately 15% in myeloma. 10,11 However, role and timing of allografting remain to be determined and convincing evidence that an allograft should routinely be performed is lacking.We report the long-term results of a trial, designed before the introduction of "new drugs," where the treatment assignment of newly diagnosed patients under the age of 66 was based on the presence or absence of an HLA-identical sibling (ClinicalTrials. gov number, NCT00415987). 12 Methods Patients and treatmentsA total of 245 patients were consecutively diagnosed with stage IIA-IIIB myeloma from September 1998 to July 2004 at 5 Italian centers: San Giovanni Battista Hospital, Tosine; University of Udine, Udine; Santa Croce e Carle Hospital, Cuneo; Sant Antonio e Biagio Hospital, Alessandrio; IRCC, Candiole. Of 199 patients, 166 with at least 1 sibling were HLA-typed to search for a potential sibling donor. Written informed consent was obtained from all patients. The study was approved by the 5 Institutional Review Boards according to the Declaration o...