Purpose: Although matched-sibling donor (MSD) hematopoietic stem-cell transplantation (HSCT) has an established role in the management of adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1), the effect of haploidentical donor (HID) HSCT as post-remission treatment for this portion of patients is not defined.Experimental Design: Transplantation outcomes from HIDs or MSDs were compared in a disease-specific, biologically phase III randomized, multicenter study. Between July 2010 and December 2013, 210 patients with Philadelphia-negative highrisk ALL in CR1 were assigned to undergo unmanipulated HIDs (121 patients) or MSDs HSCT (89 patients) according to donor availability on an intent-to-treat (ITT) basis.Results: Overall, 24 of the 210 patients had lost transplant eligibility. Therefore, 186 of 210 (88%) patients were finally transplanted from MSD (n ¼ 83) or HID (n ¼ 103). Based on the ITT principle, the 3-year disease-free survival (DFS) did not differ between HID and MSD groups [61%, 95% confidence interval (CI), 52%-70%; vs. 60%, CI, 49%-71%; P ¼ 0.91] from CR, neither did DFS differ between the two groups (68%, CI, 58%-78%; vs. 64%, CI, 52%-76%; P ¼ 0.56) from time of the graft, with cumulative incidence of nonrelapse mortality of 13% (CI, 7%-19%) and 11% (CI, 4%-18%; P ¼ 0.84) and relapse rates of 18% (CI, 10%-26%) and 24% (CI, 14%-34%; P ¼ 0.30), respectively.Conclusions: Haploidentical HSCT achieves outcomes similar to those of MSD-HSCT for Philadelphia-negative high-risk ALL patients in CR1. Such transplantation could be a valid alternative as post-remission treatment for high-risk ALL patients in CR1 lacking an identical donor.

Summary Endosperm, the major storage organ in cereal grains, determines grain yield and quality. Despite the fact that a role for P‐type pentatricopeptide repeat (PPR) proteins in the regulation of endosperm development has emerged, molecular functions of many P‐type PPR proteins remain obscure. Here, we report a rice endosperm defective mutant, floury endosperm10 (flo10), which developed smaller starch grains in starchy endosperm and abnormal cells in the aleurone layer. Map‐based cloning and rescued experiments showed that FLO10 encodes a P‐type PPR protein with 26 PPR motifs, which is localized to mitochondria. Loss of function of FLO10 affected the trans‐splicing of the mitochondrial nad1 intron 1, which was accompanied by the increased accumulation of the nad1 exon 1 and exons 2–5 precursors. The failed formation of mature nad1 led to a dramatically decreased assembly and activity of complex I, reduced ATP production, and changed mitochondrial morphology. In addition, loss of function of FLO10 significantly induced an alternative respiratory pathway involving alternative oxidase. These results reveal that FLO10 plays an important role in the maintenance of mitochondrial function and endosperm development through its effect on the trans‐splicing of the mitochondrial nad1 intron 1 in rice.

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Poor graft function (PGF) is a refractory complication that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present study, we prospectively evaluated the efficacy and safety of mesenchymal stem cells (MSCs) expanded from the bone marrow of a third-party donor to patients with PGF after allo-HSCT. Twenty patients with PGF (7 with primary and 13 with secondary PGF) received MSCs (1 × 10(6)/kg) one to three times at 28-day intervals. Seventeen patients were responsive to MSCs, whereas three were not. Within the first 100 days after MSC treatment, 13 patients developed 20 episodes of infection. Moreover, five patients experienced cytomegalovirus-DNA viremia, and seven experienced Epstein-Barr virus (EBV)-DNA viremia within the first 100 days after MSC treatment; three of the latter developed EBV-associated posttransplant lymphoproliferative disorders (PTLD) within the follow-up period. Grade II acute graft-versus-host disease (GVHD) occurred in one patient, and local chronic GVHD occurred in two patients after receiving MSC treatment, including one acute GVHD and one chronic GVHD, respectively, after accepting donor lymphocyte infusions due to PTLD. After a follow-up period of an average of 508 days (range 166-904 days) posttransplantation, 11 patients died. No short-term toxic side effects were observed after MSC treatment. Two patients experienced leukemic relapse. With the exception of three patients with PTLD, no secondary tumors occurred. These results indicate that MSCs derived from the bone marrow of a third-party donor are beneficial in the treatment of both primary and secondary PGF that develops after allo-HSCT. However, additional studies will be needed to determine whether such treatment might increase the risk of EBV infection and reactivation or the development of EBV-associated PTLD.