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Graft-versus-host disease (GVHD) occasionally leads to morbidity and mortality but is thought to reduce the risk of relapses in patients with a hematological malignancy. However, information on the effect of GVHD in pediatric leukemia is limited. Using a nationwide registry, we retrospectively analyzed 1526 children who underwent allogeneic stem cell transplantation for leukemia. Grades 0-I acute GVHD were associated with a higher relapse rate at three years after transplantation, at 25.4 and 24.3%, respectively, than grades II, III, or IV acute GVHD at 18.9%, 21.2%, and 2.6%, respectively. In contrast, the overall survival curve of the grades 0 and I GVHD groups (79.0% and 79.5%, respectively) approximated that of the grade II GVHD group (76.3%), and the probability of survival was worst in the severe GVHD groups (66.9% for grade III and 42.5% for grade IV). Chronic GVHD also reduced the relapse risk but conferred no survival advantage. Acute lymphoblastic leukemia was more sensitive to acute GVHD than acute myeloid leukemia (AML) while AML was more sensitive to chronic GVHD. Our study reproduced the preventive effects of GVHD against pediatric leukemia relapses but failed to demonstrate a significant survival advantage.

Human herpes virus-6 (HHV6)-associated myelitis and calcineurin inhibitor-induced pain syndrome (CIPS) are serious complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because these 2 complications cause similar sensory nerve-related symptoms, such as paresthesia, pruritus, and severe pain occurring around the engraftment, it can be difficult to differentially diagnose the 2 conditions. We retrospectively analyzed 435 recipients to distinguish clinical symptoms of these 2 complications. Twenty-four patients (5.5%) developed HHV6-associated encephalitis/myelitis; of these, 11 (2.5%) presented only with myelitis-related symptoms (HHV6-associated myelitis), which was confirmed by the detection of HHV6 DNA, and 8 (1.8%) had CIPS, with undetected HHV6 DNA. All patients with HHV6-associated myelitis or CIPS exhibited similar sensory nerve-related symptoms. Diagnostic images did not provide definite evidence specific for each disease. Symptoms of all patients with CIPS improved after switching to another immunosuppressant. Overall survival rate at 2 years for patients with HHV6-associated encephalitis/myelitis was significantly lower than that of CIPS (13.1% versus 29.2%; P = .049) or that of patients without HHV6-associated encephalitis/myelitis or CIPS (42.4%; P = .036), whereas there was no significant difference among the latter 2 groups (P = .889). The development of HHV6-associated encephalitis/myelitis but not CIPS was significantly associated with poor prognosis. Thus, transplant physicians should be aware that sensory nerve-related symptoms indicate early manifestations that might be correlated with reactivation of HHV6 or CIPS. Therefore, identification of HHV6 DNA is crucial for making a differential diagnosis and immediately starting appropriate treatments for each complication., (Copyright © 2018. Published by Elsevier Inc.)

Background: Pre-emptive therapy with valganciclovir (VGCV) has become the standard therapy for preventing cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT). The effectiveness of low-dose VGCV (900 mg per day) has been shown to be equal to that of standard-dose VGCV (900 mg twice daily); however, individualized optimal dosing and toxicity of VGCV have not been reported., Methods: We conducted a retrospective study to evaluate the optimal dose of VGCV as pre-emptive therapy for preventing CMV infection by comparing the frequency of adverse events (AEs) and clinical efficacy in a low-dose VGCV group with those in a standard-dose VGCV group. Thirty-eight patients who were administered VGCV because of CMV antigenemia after HSCT were analyzed., Results: Neutropenia (standard-dose group: 33%, low-dose group: 15%, P = 0.26) and thrombocytopenia (standard-dose group: 39%, low-dose group: 15%, P = 0.14) were frequent AEs of VGCV, and a significantly higher frequency of overall AEs was detected in the standard-dose group than in the low-dose group (P < 0.01). In comparison of dosage based on weight, dosage of VGCV >27 mg/kg was closely related to onset of AEs (P = 0.04)., Conclusions: Low-dose VGCV was not inferior in clinical efficacy, including clearance rate of CMV antigenemia and incidence of consequent CMV disease, to standard-dose VGCV as was previously reported. Initial low-dose VGCV for pre-emptive CMV therapy markedly reduces hematologic toxicity and has clinical efficacy equivalent to that of standard-dose VGCV. It is therefore reasonable for patients, except for noticeably overweight patients, to be given initial low-dose VGCV., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In this issue of Blood, Varelias and colleagues demonstrate a central role of interleukin (IL)-6 in idiopathic pneumonia syndrome (IPS) after allogeneic stem cell transplantation (SCT) in both mice and humans.

Background: Reactivation of hepatitis B virus (HBV) infection, reverse seroconversion (RS), is a serious complication after allogeneic stem cell transplantation (alloHSCT). We previously conducted a post-transplant hepatitis B vaccine intervention trial and demonstrated the vaccine efficacy in preventing HBV-RS. This report is an update of the hepatitis B vaccine study., Methods: In this trial, 21 patients were enrolled and received a standard 3-dose regimen of hepatitis B vaccine after discontinuation of immunosuppressants, whereas 25 transplant recipients with previous HBV infection did not receive the vaccine and served as controls., Results: None of the 21 patients in the vaccine group developed HBV-RS and 12 controls developed HBV-RS in median follow-up periods of 60 months (range 13-245). HBV vaccine resulted in a positive value of hepatitis B surface antibody (HBsAb) titer in 9 patients, while HBsAb remained negative in 12 patients. Presence of a high titer of HBsAb before vaccination was associated with conversion into HBsAb positivity after vaccination., Conclusion: These results demonstrated the long-term effects of HBV vaccine for preventing HBV-RS after alloHSCT. Of note, no HBV-RS occurred, even in patients who did not achieve conversion into HBsAb positivity after vaccination., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Consolidation therapy for patients with multiple myeloma (MM) has been widely adopted to improve treatment response following autologous stem cell transplantation. In this study, we retrospectively analyzed the safety and efficacy of combination regimen of bortezomib, thalidomide, and dexamethasone (VTD) as consolidation therapy in 24 Japanese patients with newly diagnosed MM. VTD consisted of bortezomib at a dose of 1.3 mg/m(2) and dexamethasone at a dose of 40 mg/day on days 1, 8, 15, and 22 of a 35-day cycle, with daily oral thalidomide at a dose of 100 mg/day. Grade 3-4 neutropenia and thrombocytopenia were documented in four and three patients (17 and 13 %), respectively, but drug dose reduction due to cytopenia was not required in any case. Peripheral neuropathy was common (63 %), but severe grade 3-4 peripheral neuropathy was not observed. Very good partial response or better response (≥VGPR) rates before and after consolidation therapy were 54 and 79 %, respectively. Patients had a significant probability of improving from

We retrospectively analyzed the outcomes of 26 patients with acute promyelocytic leukemia (APL) in the first CR (CR1) or second CR (CR2), who underwent autologous PBSCT (auto-PBSCT) between 1992 and 2008. All patients received all-trans retinoic acid-based induction therapy. After two courses of consolidation chemotherapy, upfront auto-PBSCT was performed in 20 patients in the CR1. Five patients had a high WBC count of more than 10 × 109/L (high risk), while 15 patients had a count of less than 10 × 109/L (low risk) at initial presentation. In addition, six patients, who were considered as low-risk patients at presentation, had a relapse after three cycles of consolidation and 2 years of maintenance therapy, but gained the molecular remission after re-induction and consolidation, and underwent auto-PBSCT in the CR2. In 26 recipients, engraftment was rapid and no TRM was documented. All 20 patients autotransplanted in CR1 were still in CR at a median of 133 months (73-193 months), and six patients who underwent auto-PBSCT in CR2 were also still in CR at a median of 41 months (2-187 months) without maintenance therapy. PML/RARα chimeric mRNA was undetectable in PBSC or BM samples examined before auto-PBSCT. Despite a small number of cases studied, our retrospective observations suggest that auto-PBSCT may be an effective treatment option to continue durable CR in the treatment of high-risk APL. We review previous reports and discuss the role of autotransplantation in the treatment of APL patients in CR. [ABSTRACT FROM AUTHOR]

Long-term analysis of infectious complication after high-dose immunosuppressive therapy with CD34-selected autologous hematopoietic stem cell transplantation for patients with severe autoimmune diseases (AD) was performed. Theoretically, CD34 selection can reduce the risk of reinfusion of autoreactive lymphocytes. However, it is also associated with a significant reduction in T cells, natural killer cells, and monocytes, which in turn may compromise immune reconstitution, thereby increasing the risk of infection. Moreover, AD compromises host immunity and causes organ damage resulting in dysfunction of the cutaneous or mucosal barrier. In this study, the incidence rate of infections is reported in 14 patients who underwent high-dose (200 mg/kg) cyclophosphamide therapy followed by reinfusion of CD34-selected autologous peripheral blood stem cells. Bacterial complication occurred in 3 of 14 (21%) patients. Cytomegalovirus reactivation and adenovirus hemorrhagic cystitis were observed in 9 (64%) and 2 (14%) patients, respectively. As for late infectious complications, 7 patients (50%) developed dermatomal varicella zoster virus infection. No infection-related mortality was seen in this case series. Because the risk for infections approaches that seen in allogeneic transplant recipients, infection surveillance, diagnostic workup, and prophylactic strategies similar to those applicable to allogeneic recipients are warranted. [ABSTRACT FROM AUTHOR]

T. Aoki, K. Kamezaki, T. Miyamoto, K. Nagafuji, Y. Mori, T. Yamauchi, K. Takenaka, H. Iwasaki, N. Harada, N. Shimono, T. Teshima, K. Akashi. Cord blood stem cell transplantation in a patient with disseminated mucormycosis and acute myelogenous leukemia. Transpl Infect Dis 2010: 12: 277–279. All rights reserved [ABSTRACT FROM AUTHOR]

Abstract Objective To elucidate the mechanisms by which orally administered tacrolimus was not absorbed in a patient following allogeneic hematopoietic stem cell transplantation. Clinical Course A 17-year-old girl with acute myeloid leukemia underwent HLA-haploidentical peripheral blood stem cell transplantation following fludarabine, busulfan, and total-body irradiation. Graft-vs-host disease prophylaxis was post-transplant cyclophosphamide, followed by intravenous tacrolimus and mycophenolate mofetil. When tacrolimus was switched to oral administration, its blood level declined rapidly, resulting in development of acute graft-vs-host disease, which was ameliorated by switching back to intravenous administration. Methods/Results To elucidate if impaired tacrolimus absorption could be related to genetic polymorphism of tacrolimus-metabolizing enzymes, we analyzed gene polymorphisms of cytochrome P450 3A4, cytochrome P450 3A5, and multidrug resistance 1 (MDR1). The patient had wild-type cytochrome P450 3A4 (*1/*1) and variant-type cytochrome P450 3A5 (*3/*3), while MDR1 genes (2677A/G, 3435C/C) were wild-type. Conclusion Wild-type MDR1 gene product P-glycoprotein expressed in the intestine reduces drug absorption from the gastrointestinal tract and may have contributed to low blood levels of tacrolimus in this patient when tacrolimus was orally administered. Highlights • The patient's gene polymorphism of tacrolimus-metabolizing enzymes, especially MDR1, may be associated with insufficient absorption and lack of increase in blood level of tacrolimus when orally administered following allogeneic hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]