Early posttransplantation donor-derived invariant natural killer T-cell recovery predicts the occurrence of acute graft-versus-host disease and overall survival

Invariant natural killer T (iNKT) cells can experimentally dissociate GVL from graft-versus-host-disease (GVHD). Their role in human conventional allogeneic hematopoietic stem cell transplantation (HSCT) is unknown. Here, we analyzed the post-HSCT recovery of iNKT cells in 71 adult allografted patients. Results were compared with conventional T- and NK-cell recovery and correlated to the occurrence of GVHD, relapse, and survival. We observed that posttransplantation iNKT cells, likely of donor origin, recovered independently of T and NK cells in the first 90 days after HSCT and reached greater levels in recipient younger than 45 years (P = .003) and after a reduced-intensity conditioning regimen (P = .03). Low posttransplantation iNKT/T ratios (ie, < 10(-3)) were an independent factor associated with the occurrence of acute GVHD (aGVHD; P = .001). Inversely, reaching iNKT/T ratios > 10(-3) before day 90 was associated with reduced nonrelapse mortality (P = .009) without increased risk of relapse and appeared as an independent predictive factor of an improved overall survival (P = .028). Furthermore, an iNKT/T ratio on day 15 > 0.58 × 10(-3) was associated with a 94% risk reduction of aGVHD. These findings provide a proof of concept that early postallogeneic HSCT iNKT cell recovery can predict the occurrence of aGVHD and an improved overall survival.     

Autologous stem cell transplantation in mantle cell lymphoma: a report from the SFGM-TC

Autologous stem cell transplantation (ASCT) is considered as an attractive treatment option for young mantle cell lymphoma (MCL) patients. This retrospective SFGM-TC study analyzed the outcome of 500 MCL patients treated with ASCT and investigated parameters that may modify the outcome of patients who proceeded to ASCT upfront (n?=?396). For all patients, median age at ASCT was 56 years (range, 26–71). Median follow-up was 34 months. Three-year progression free survival (PFS) and overall survival (OS) were 63.5 % [95 % CI, 58.7–68.6 %] and 79.5 % [95 % CI, 75.3–83.4 %], respectively. Median time from ASCT to relapse was 22 months (range, 0–136 m). For patients transplanted upfront and in multivariate analysis, age (HR?=?2 [1.2–3.4], p?=?.01, and HR?=?2.3 [1.2–4.5], p?=?.01), disease status at time of ASCT (HR?=?1.7 [1.1–2.6], p?=?.01 and HR?=?1.8 [1.1–3.1], p?=?.03), and use of rituximab (HR?=?0.5 [0.3–0.8], p?=?.002 and HR?=?0.5 [0.3–0.9], p?=?.01) were statistically predictive for both PFS and OS. Also, first line treatment including anthracycline and high-dose cytarabine followed by ASCT conditioned with TAM improved PFS. To conclude, this study suggests that ASCT in MCL can provide a high response rate but may not be sufficient to cure MCL even when ASCT is performed upfront, highlighting the need for innovative approaches before ASCT, aiming to increase complete response rate, and after ASCT, to maintain response.     

Allogeneic haematopoietic stem cell transplantation for myelofibrosis: a report of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

Allogeneic haematopoietic stem‐cell transplantation (HSCT) is the only curative treatment for myelofibrosis. We report an analysis of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM‐TC) registry including patients with myelofibrosis transplanted between 1997 and 2008. Potential risk factors affecting engraftment, non‐relapse mortality (NRM), overall survival (OS) and progression‐free survival (PFS) were analysed. One hundred and forty‐seven patients, aged 20–68 (median 53) years, diagnosed with primary (53%) or secondary myelofibrosis underwent HSCT; 59% of patients were transplanted from a matched sibling donor. The conditioning regimen was myeloablative in 31% of patients. Ninety percent of the patients engrafted. Factors affecting favourably engraftment were splenectomy before HSCT, human leucocyte antigen (HLA) matched sibling donor, peripheral stem cell use as source of stem cells and absence of pre‐transplant thrombocytopenia. Four‐year OS, PFS and NRM survival were 39% (95%confidence interval [CI]: 31–50), 32% (95%CI: 24–43) and 39% (95%CI 30–48), respectively. Multivariate analysis indicated that HLA‐identical sibling donor, chronic phase disease and splenectomy in men had favourable impact on OS.     

Interest of high-dose pulse corticosteroid therapy combined with methotrexate for severe alopecia areata: a retrospective case series

Background: The combination of systemic pulse corticosteroids and methotrexate in the treatment of severe alopecia areata has never been reported. Objective: The objective of this work was to give arguments for the efficacy and safety of this combined treatment. Methods: This was a retrospective case series of patients treated with intravenous 500 mg methylprednisolone per day for 3 consecutive days monthly during 3 months plus methotrexate initiated at the end of the second pulse regimen. We reviewed all case notes of patients who received this regimen between January 1 2007 and December 1 2010. Results: Twenty patients were treated. Data on hair regrowth at month 12 were available for all patients; 14 patients were still receiving the treatment on December 1 2010, 2 patients were lost of follow-up, and 4 patients had stopped the treatment. Of the 14 patients who were still receiving the treatment regimen at month 18, 10 (10/20, 50%) had total hair regrowth and 4 (4/20, 20%) had incomplete but satisfactory hair regrowth. The treatment was well tolerated. Conclusion: The initial treatment by pulse intravenous corticosteroids may influence the overall response. This approach should be evaluated in a larger series of patients.