ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses.

The poly(ADP-ribose) polymerases (PARPs) participate in many biological and pathological processes. Here we report that the PARP-13 shorter isoform (ZAPS), rather than the full-length protein (ZAP), was selectively induced by 5'-triphosphate-modified RNA (3pRNA) and functioned as a potent stimulator of interferon responses in human cells mediated by the RNA helicase RIG-I. ZAPS associated with RIG-I to promote the oligomerization and ATPase activity of RIG-I, which led to robust activation of IRF3 and NF-κB transcription factors. Disruption of the gene encoding ZAPS resulted in impaired induction of interferon-α (IFN-α), IFN-ß and other cytokines after viral infection. These results indicate that ZAPS is a key regulator of RIG-I signaling during the innate antiviral immune response, which suggests its possible use as a therapeutic target for viral control.

Donor lymphocyte infusion after haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia.

Although haploidentical donor lymphocyte infusion (DLI) is a valid treatment option for relapsed acute myeloid leukemia (AML), the incidence and risk factors for graft-versus-host disease (GVHD) and the efficacy of haploidentical DLI have not been fully evaluated. We retrospectively analyzed the outcomes after haploidentical DLI for 84 patients with AML using a nationwide database and additional questionnaires. The median number of DLI cycles and infused CD3+ cell dose was 1 and 1.0 × 106/kg, respectively. The infused CD3+ cell count of 5.0 × 105/kg or higher was associated with acute GVHD (grade II-IV, 32.1% vs. 10.5%, p = 0.03; grade III-IV, 21.4% vs. 5.3%, p = 0.10). Patients who developed grade III-IV acute GVHD more frequently succumbed to treatment-related mortality (46.7% vs. 15.8% at 1 year, p = 0.002), although the relapse-related mortality was significantly low (40.0% vs. 72.2% at 1 year, p = 0.025). The overall response to DLI was significantly higher in the preemptive DLI group (47.4%) than in the therapeutic group (13.9%, p = 0.002). In the multivariate analysis, preemptive DLI was the predictive factor for overall response (odds ratio, 5.58; p = 0.003). Our results indicated the substantial risk of acute GVHD after haploidentical DLI with CD3+ cell count of 5.0×105/kg or higher and the favorable outcomes after preemptive DLI.

[Leukemia Relapse as Granulocytic Sarcoma Beginning with Penile Localization : A Case Report].

A 57-year-old man visited the urology department with a painful mass on the dorsal side of the penis. Magnetic resonance imaging sagittal image showed a small nodule. Leukemia recurrence was suspected due to his history of treatment for acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation. No recurrence was identified by bone marrow biopsy ; however, two months later, the recurrence of leukemia was strongly suspected because the tumor grew over time and blasts were found in the peripheral blood. A biopsy of the penile tumor and bone marrow was performed, leading to the diagnosis of granulocytic sarcoma. Patients with a history of leukemia may be preceded by a single recurrence to extramedullary organs, even if blood and bone marrow findings suggest remission.

[Antithymocyte globulin for graft-versus-host disease prophylaxis, past, present and future].

Antithymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis has been demonstrated for chronic GVHD inhibition by a series of randomized control trials. The optimal dose of ATG remained unestablished; however, the recommended dose of ATG by the European Group for Blood and Marrow Transplantation has recently decreased. While a lower ATG dose has been used in Japan, ATG usage is recommended in peripheral blood stem cell transplantation or human leukocyte antigens (HLA) 1-locus mismatched bone marrow transplantation with myeloablative conditioning from the nation-wide retrospective studies showing that ATG inhibited chronic GVHD and improved GVHD-free, relapse-free survival. The association of absolute lymphocyte counts (ALC) before ATG administration with transplant outcomes has been reported, which suggests a possible strategy to individualize the ATG dose according to ALC before ATG. Recent studies compared the transplant outcomes using ATG and post-transplant cyclophosphamide, which has rapidly spread in haploidentical transplantation; however, further studies are needed to establish those positioning in HLA-matched/mismatched transplantation.

Effect of Cytomegalovirus Reactivation With or Without Acute Graft-Versus-Host Disease on the Risk of Nonrelapse Mortality.

BACKGROUND: Despite a strong association between acute graft-versus-host disease (GVHD) and cytomegalovirus reactivation (CMVR), the joint effect of acute GVHD and CMVR on nonrelapse mortality (NRM) has not been well studied. METHODS: We evaluated the impact of CMVR on NRM stratified according to the development of acute GVHD using a landmark method. This study included 6078 patients who received their first allogeneic hematopoietic cell transplantation (HCT) with a preemptive strategy for CMVR between 2008 and 2017. RESULTS: The cumulative incidences of grade 2-4 acute GVHD (G24GVHD), CMVR by day 100, and CMV disease by day 365 were 37.3%, 52.1%, and 2.9%, respectively. Patients with G24GVHD were associated with the subsequent development of CMVR, and the presence of CMVR also increased the risk of G24GVHD. In a landmark analysis at day 65, the cumulative incidence of NRM at 1 year was 5.4%, 10.0%, 13.9%, and 19.7% in patients with G24GVHD-/CMVR-, G24GVHD-/CMVR+, G24GVHD+/CMVR-, and G24GVHD+/CMVR+, respectively. In a multivariate analysis, CMVR was respectively associated with an increased risk of NRM by day 365 in patients without G24GVHD (hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.24-2.05; P < .001) and with G24GVHD (HR, 1.34; 95% CI, 1.06-1.70; P = .014), but the interaction between G24GVHD and CMVR was not significant (P = .326). Subgroup analyses suggested that the joint effect of acute GVHD and CMVR might vary according to the baseline characteristics. CONCLUSIONS: These data regarding the close relationship between acute GVHD and CMVR should provide important implications for the treatment strategy after HCT.

Residual disease is a strong prognostic marker in patients with acute lymphoblastic leukaemia with chemotherapy-refractory or relapsed disease prior to allogeneic stem cell transplantation.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is one of the curative treatment options for acute lymphoblastic leukaemia (ALL). However, the outcomes in patients transplanted without complete remission (non-CR) have not yet been fully reported, and detailed analyses are required to identify subgroups in which optimal prognosis is expected and to optimize pre-transplant therapeutic strategies. Hence, we performed a multicentred retrospective cohort study including a total of 663 adult ALL patients transplanted at non-CR status; the median bone marrow (BM) blast counts at HSCT was 13·2%, and 203 patients (30·6%) were treated at primary induction failure status. The overall survival (OS) was 31·1% at two years, and the multivariate analyses identified five prognostic risk factors, including older age (≥50 years), increased BM blasts (≥10%), poor performance status, high haematopoietic cell transplantation (HCT)-comorbidity index, and relapsed disease status, among which BM blast was the most significantly related. A predictive scoring system composed of these risk factors clearly stratified OS (15·6-59·5% at two years). In conclusion, this is the first large-scale study to analyze the correlation of patient characteristics with post-transplant prognosis in ALL transplanted at non-CR status. The importance of blast control before HSCT should be focused on for better patient prognosis.

High lymphocyte counts before antithymocyte globulin administration predict acute graft-versus-host disease.

Antithymocyte globulin (ATG) reduces severe acute and chronic graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (PBSCT). However, risk factors for severe acute GVHD in PBSCT using ATG remain to be determined. We conducted a single-center, retrospective study to analyze the association of acute GVHD requiring systemic corticosteroid (SC-aGVHD) with absolute lymphocyte counts (ALC) before the administration of ATG or conditioning in 53 patients with HLA-matched PBSCT using low-dose thymoglobulin (2 mg/kg) after myeloablative conditioning. The cumulative incidence of SC-aGVHD was 17.0% and ALC before ATG were significantly higher in patients with SC-aGVHD compared to that in patients without it (median, 0.15 × 109/L vs 0.06 × 109/L, P = 0.047). The cumulative incidence of SC-aGVHD was significantly higher in patients with high ALC before ATG (≥ 0.15 × 109/L) than in those with low ALC (38.5% vs 10.0%, P = 0.016). Non-relapse mortality (NRM) was also significantly higher in the high ALC before ATG group than the low ALC before ATG group (2-year NRM: 23.9% vs 6.0%, P = 0.048), leading to worse survival (2-year overall survival: 69.2% vs 83.5%, P = 0.039). Our study suggested that high ALC before ATG is a risk factor for SC-aGVHD.

Cytomegalovirus reactivation is associated with an increased risk of late-onset invasive aspergillosis independently of grade II-IV acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation: JSTCT Transplant Complications Working Group.

There is a matter of debate about the clinical impact of cytomegalovirus (CMV) reactivation on the development of late-onset invasive aspergillosis (IA), which occurs 40 days or later after allogeneic hematopoietic stem cell transplantation (HSCT). Using a Japanese transplant registry database, we analyzed the risk factors for the development of late-onset IA in 21,015 patients who underwent their first allogeneic HSCT between 2006 and 2017. CMV reactivation was defined as the initiation of preemptive anti-CMV antiviral therapy. Overall, there were 582 cases of late-onset IA, which occurred at a median of 95 days after HSCT. The 2-year cumulative incidence was 3.4% (95% confidence interval (CI), 3.0-3.9) in patients with CMV reactivation within 40 days after HSCT and 2.5% (95% CI, 2.3-2.8) in those without it (P < 0.001). In a multivariate analysis, CMV reactivation as a time-dependent covariate was significantly associated with the development of late-onset IA (hazard ratio (HR) 1.40, P < 0.001), as well as grade II-IV acute GVHD, age > 50 and HCT-CI ≥ 3 in the entire cohort. If we focus on the subgroup without grade II-IV acute GVHD, which is generally an indication for systemic corticosteroid therapy (n = 12,622), CMV reactivation was still a significant factor for the development of late-onset IA (HR 1.37, P = 0.045) as well as age > 50 years, HCT-CI ≥ 3, and cord blood transplantation. In conclusion, CMV reactivation was associated with an increased risk of late-onset IA after allogeneic HSCT independently of acute GVHD. Close monitoring for late-onset IA is necessary for patients who develop CMV reactivation even without grade II-IV acute GVHD.

[Antithymocyte globulin for GVHD prophylaxis in allogeneic hematopoietic stem cell transplantation].

Graft versus host disease (GVHD) prophylaxis using antithymocyte globulin (ATG) has been shown for chronic GVHD inhibition effect by a series of randomized control trials in unrelated hematopoietic or peripheral blood stem cell transplantation (PBSCT). Lower doses of ATG have been used in recent studies, although the optimal dose of ATG remains undefined. Consequently, a multicenter phase II study of low-dose ATG (2 mg/kg Thymoglobulin®) was conducted in patients undergoing human leukocyte antigen-matched PBSCT, showing the safety and efficacy for the prevention of both acute and chronic GVHD. In a nationwide retrospective study for ATG in unrelated PBSCT, the ATG group had a significantly lower incidence of chronic GVHD and a higher probability of GVHD- and relapse-free survival compared with the non-ATG group, although the dose of ATG used was low (1.0-3.0 mg/kg of Thymoglobulin®). Regarding absolute lymphocyte count (ALC) before the administration of ATG, the incidences of grades III-IV acute GVHD and moderate-to-severe chronic GVHD were significantly higher in patients with high ALC before ATG. Conversely, the relapse rate was significantly higher in patients with low ALC before ATG, suggesting a strategy to individualize ATG dosing by modulating ATG doses according to ALC before ATG.

Outcome of allogeneic hematopoietic stem cell transplantation for mycosis fungoides and Sézary syndrome.

Although allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to provide prolonged remission of relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS), its role has not been fully evaluated. Here, the outcomes of allogeneic HSCT for patients with MF/SS were retrospectively evaluated by using the registry database of the Japan Society for Hematopoietic Cell Transplantation. Forty-eight patients were evaluable and enrolled in the analysis. Median age was 45.5 years. Eighteen patients (38%) received myeloablative conditioning, and 33 (69%) received HSCT from an alternative donor. Disease status was complete or partial response in 25% of the patients and relapsed or refractory in the others. At the time of analysis, 18 patients were alive, with a median follow-up of 31.0 months (range, 3.8-31.1). Three-year overall survival (OS) and progression-free survival (PFS) were 30% (95%CI, 16-45%) and 19% (95%CI, 9-31%), respectively. Disease progression was not observed later than 17 months after transplantation. Both disease status and performance status at transplant significantly affected OS and PFS. Although our findings suggest that allogeneic HSCT provides long-term PFS in patients with MF/SS, the timing of transplantation should be decided carefully based on the disease status and the patient's condition in order to improve the outcome.

Low incidence of posttransplant lymphoproliferative disorder after allogeneic stem cell transplantation in patients with lymphoma treated with rituximab.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication after hematopoietic stem cell transplantation (HSCT). Several studies of risk factors for PTLD have been reported; however, the probability of, and risk factors for, PTLD in patients with lymphoma is unknown. Japanese nationwide transplant registry data from 5270 patients with lymphoma after allogeneic HSCT were analyzed. Mature B-cell, T/NK-cell, and T-cell lymphoblastic subtypes accounted for 49%, 26%, and 9.6% of lymphoma cases, respectively. Rituximab was used in 1678 lymphoma patients, most of whom (89%) received HSCT for mature B-cell lymphoma. Thirty-one patients with lymphoma developed PTLD, representing a probability of 0.77% at 2 years post-HSCT, which did not differ significantly from that in patients with other diseases (P = .98). Year of HSCT after 2010 (hazard ratio [HR] = 5.6, 95% confidence interval [CI], 1.48-21.3), antithymocyte globulin (ATG) use in the conditioning regimen (HR = 4.5, 95% CI, 1.61-12.5), and no rituximab use before HSCT (HR = 3.2, 95% CI, 1.26-7.90) were identified as risk factors for PTLD. Probabilities of PTLD at 1 year post-HSCT according to rituximab and ATG use were 0.23% (rituximab+, ATG-), 0.75% (rituximab-, ATG-), 1.25% (rituximab+, ATG+), and 3.53% (rituximab-, ATG+). Regarding lymphoma subtypes, patients with mature B-cell lymphoma had the lowest incidence of PTLD (0.35% at 2 years). Among high-risk patients receiving ATG, the mortality rate due to infection was elevated in those previously treated with rituximab (22%) relative to those without (14%); however, the difference was not significant (P = .10). Rituximab use before HSCT significantly reduces the risk of PTLD. Adding rituximab to the conditioning regimen is potentially a good strategy to prevent the development of PTLD in high-risk patients.

Reduced dose of MTX for GVHD prophylaxis promotes engraftment and decreases non-relapse mortality in umbilical cord blood transplantation.

Although a combination of calcineurin inhibitor and methotrexate (MTX) is used for graft-versus-host disease (GVHD) prophylaxis in umbilical cord blood transplantation (CBT), optimal dose of MTX for CBT remains to be determined.We conducted a retrospective study to evaluate the safety and efficacy of standard-dose MTX (St-MTX, 15 mg/m2 on day 1 and 10 mg/m2 on days 3 and 6) and mini-dose MTX (Mini-MTX, 5 mg/m2 on days 1, 3 and 6) for GVHD prophylaxis in patients who underwent single unit CBT against hematological malignancies.Thirty-two and 26 patients received St-MTX and Mini-MTX, respectively. Cumulative incidence of neutrophil engraftment was significantly higher in the Mini-MTX group than in the St-MTX group (88.5% vs 65.6%, P = 0.00448). Cumulative incidences of grade II to IV and grade III to IV of acute graft-versus-host disease (GVHD) were 34.4% and 6.2% in the St-MTX group, and 34.6% and 7.7% in the Mini-MTX group with no statistical significance. One-year non-relapse mortality (NRM) was significantly lower in the Mini-MTX group compared to the St-MTX group (31.2% vs 3.8%, P = 0.00938), whereas relapse rate was not different between the groups. Multivariate analysis also indicated that Mini-MTX significantly improved engraftment (HR, 0.5359; 95% CI, 0.3082 to 0.9318; P = 0.0270) and reduced NRM (HR, 0.117; 95% CI, 0.0151 to 0.9067; P = 0.040).Our study suggests that GVHD prophylaxis using Mini-MTX in CBT is feasible and associated with improvement of engraftment and reduction in NRM.

Feasibility and efficacy of low-dose pegfilgrastim for CD34+ cell mobilization in lymphoma.

BACKGROUND: Pegfilgrastim has equivalent efficacy to daily granulocyte colony-stimulating factor (G-CSF) in enhancing neutrophil recovery after chemotherapy, but data on its use for peripheral blood stem cell (PBSC) mobilization are limited. We evaluated the safety and efficacy of CD34+ PBSC mobilization by low-dose (3.6 mg) pegfilgrastim after chemotherapy in patients with malignant lymphoma. STUDY DESIGN AND METHODS: Twenty patients with malignant lymphoma were enrolled in this study. Cytotoxic chemotherapy was started on day 1, and 3.6 mg of pegfilgrastim was subcutaneously administered on day 7. CD34+ cells were counted in the peripheral blood daily from days 11 to 14 using a flow cytometric analysis. RESULTS: In 19 of the 20 patients (95%), the CD34+ cell counts in the peripheral blood exceeded 10 × 106/L, with a mean value of 20.3 on day 11, 38.0 on day 12, 40.3 on day 13, and 40.1 on day 14. Older age was associated with lower maximum CD34+ cell mobilization. The most frequent adverse events associated with pegfilgrastim were back pain, nausea, appetite loss, and lactate dehydrogenase elevation. CONCLUSION: Our data indicated that a single dose of 3.6 mg pegfilgrastim on day 7 after chemotherapy safely and effectively mobilized CD34+ cells.

Tyrosine kinase inhibitor prophylaxis after transplant for Philadelphia chromosome-positive acute lymphoblastic leukemia.

Tyrosine kinase inhibitor (TKI) administration after allogeneic hematopoietic stem cell transplantation (HSCT) may carry a survival benefit in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Therefore, we investigated whether TKI prophylaxis for negative-minimal residual disease (MRD) after HSCT would improve patient outcomes in this nationwide retrospective cohort study. We included patients with Ph+ ALL who underwent their first allogeneic HSCT between 2001 and 2016, received TKI before HSCT, and achieved negative-MRD status within 180 days after HSCT. Of 850 patients for inclusion, 50 patients received TKI prophylaxis, mostly imatinib or dasatinib (median dose: 400 mg with imatinib and 40 mg with dasatinib). In a multivariate analysis, disease status at HSCT was the sole risk factor for relapse (hazard ratio, 3.58; P < .001 for positive-MRD with complete remission [CR] and hazard ratio, 6.13; P < .001 for active disease). TKI prophylaxis was not associated with a decreased risk of relapse or superior overall survival in either the whole cohort or in the analysis limited to negative-MRD or positive-MRD with CR1 at HSCT. Meanwhile, TKI prophylaxis limited to dasatinib might be associated with a decreased risk of relapse (hazard ratio, 0.34; P = .140), unlike imatinib. Alternative strategies using new-generation TKI for high-risk patients are warranted to improve the outcomes after allogeneic HSCT.

Impact of High-Frequency HLA Haplotypes on Clinical Cytomegalovirus Reactivation in Allogeneic Hematopoietic Stem Cell Transplantation.

Some studies support the hypothesis that HLA genes and haplotypes evolved by natural selection through their protective abilities against specific infectious pathogens. However, very little is known regarding the impact of high-frequency HLA haplotypes on the risk of relevant infectious diseases among a given ethnic group. We evaluated the impact of high-frequency HLA haplotypes on cytomegalovirus (CMV) reactivation and infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a Japanese population as a model of infectious disease that has coexisted with humans. A total of 21,127 donor-patient pairs were analyzed. HLA-A-B-DRB1 haplotypes were estimated using the maximum probability algorithm. Seven haplotypes with >1% frequency were defined as high-frequency haplotypes (HfHPs). Homozygotes of HfHP and heterozygotes had significantly lower risk of CMV reactivation and infection (hazard ratio [HR] = 0.88, P = .009 and HR = 0.93, P = .003, respectively) than homozygotes of low-frequency HLA haplotypes (LfHPs). In subgroup analyses of a different donor source, these associations were statistically significant in unrelated donor transplants. Finally, CMV risk for homozygotes and heterozygotes of each HfHP was compared with that of homozygotes of LfHPs. The 2 most predominant HfHP groups (A*24:02-B*52:01-DRB1*15:02 group and A*24:02-B*07:02-DRB1*01:01 group) had a significantly lower risk of CMV reactivation and infection (HR = 0.86, P < .001 and HR = 0.91, P = .033, respectively). Our findings suggest that HfHPs may be protective against CMV reactivation and infection and that increased care regarding CMV reactivation and infection may be necessary for patients with LfHP after allo-HSCT.

Risk Factors and Predictive Scoring System For Post-Transplant Lymphoproliferative Disorder after Hematopoietic Stem Cell Transplantation.

We analyzed data from 64,539 consecutive patients in the Japanese national transplant registry, including 40,195 after allogeneic hematopoietic stem cell transplantation (HSCT), 24,215 after autologous HSCT and 129 after syngeneic HSCT, of whom 299 developed Epstein-Barr virus-positive post-transplant lymphoproliferative disorder (PTLD). The probability of developing PTLD at 2 years post-HSCT was .79% after allogeneic transplantation, .78% after syngeneic transplantation, and .11% after autologous transplantation. The following variables were identified as risk factors after allogeneic HSCT in multivariate analysis: antithymocyte globulin (ATG) use in a conditioning regimen, ATG use for acute graft-versus-host disease (GVHD) treatment, donor other than an HLA-matched related donor, aplastic anemia, second or subsequent allogeneic HSCT, the most recent year of transplantation, and acute GVHD. The probability at 2 years increased particularly after 2009 (1.24%) than before 2009 (.45%). To stratify the risk of PTLD before allogeneic HSCT, we developed a novel 5-point scoring system based on 3 pretransplant risk factors: ATG use in a conditioning regimen (high dose, 2 points; low dose, 1 point), donor type (HLA-mismatched related donor, 1 point; unrelated donor, 1 point; cord blood, 2 points), and aplastic anemia (1 point). Patients were classified into 4 risk groups according to the summed points: low risk (0 or 1 point), intermediate risk (2 points), high risk (3 points), and very high risk (4 or 5 points) groups, with probabilities at 2 years of .3%, 1.3%, 4.6%, and 11.5%, respectively. Our scoring system is useful for predicting patients at high risk for PTLD. Careful observation and close monitoring of Epstein-Barr virus reactivation are warranted for these high-risk patients.

Induction chemotherapy followed by allogeneic HCT versus upfront allogeneic HCT for advanced myelodysplastic syndrome: A propensity score matched analysis.

To reduce post-transplant relapse, acute myeloid leukemia (AML) type remission induction chemotherapy has been attempted to reduce disease burden before allogeneic hematopoietic cell transplantation (HCT) in patients with advanced myelodysplastic syndrome (MDS). However, the efficacy of induction chemotherapy before HCT is unclear. We retrospectively analyzed the Japanese registration data of 605 adult patients, who had received allogeneic HCT for advanced MDS between 2001 and 2016, to compare the post-transplant relapse between patients who received induction chemotherapy followed by allogeneic HCT and those who received upfront HCT. Propensity score matching identified 230 patients from each cohort. There were no significant differences in overall survival and non-relapse mortality between the two groups. The cumulative incidence of relapse was significantly higher in patients who received induction chemotherapy than those who received upfront HCT. In the subgroup analyses, upfront HCT had a significantly reduced relapse incidence among patients with poor cytogenetics, those with higher international prognostic scoring system at diagnosis, and those who received reduced-intensity conditioning. Our results suggested that AML type remission induction chemotherapy before HCT did not improve post-transplant relapse and survival for adult patients with advanced MDS. Upfront HCT is preferable for patients with a poor karyotype.

Hematogones Predict Better Outcome in Allogeneic Hematopoietic Stem Cell Transplantation Irrespective of Graft Sources.

Benign precursors of B lymphocytes, termed hematogones, are observed in the regenerative state of hematopoiesis following chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have demonstrated that expansion of hematogones correlates with better clinical outcomes after allo-HSCT. We retrospectively analyzed the association between hematogones and clinical outcomes in 309 consecutive patients who underwent allo-HSCT, which is the largest population-based cohort reported so far. The incidence of hematogones was significantly higher in complete remission (CR) patients at the time of transplantation than in non-CR patients, after myeloablative conditioning than after reduced-intensity conditioning, with tacrolimus-based graft-versus-host disease (GVHD) prophylaxis than with cyclosporine-based prophylaxis, and with disease other than malignant lymphoma (all P < .05). Patients with hematogones developed less acute GVHD and infections than did those without them (P < .05). Emergence of hematogones was associated with superior GVHD-free relapse-free survival and lower nonrelapse mortality, and was an independent prognostic factor for overall survival, irrespective of donor sources.

The association between the incidence of intestinal graft-vs-host disease and antibiotic use after allogeneic hematopoietic stem cell transplantation.

Intestinal microbiota plays an important role in the regulation of allogeneic immune reaction after allogeneic hematopoietic stem cell transplantation (allo-SCT). Intestinal graft-vs-host disease (GVHD) is one of the major causes of mortality after allo-SCT and often complicated with intestinal dysbiosis. Recent studies suggest that antibiotic-induced dysbiosis is a risk factor for intestinal GVHD. We retrospectively evaluated the impacts of antibiotic use on the incidence of intestinal GVHD occurring before day 100 after allo-SCT. Among 213 patients who underwent allo-SCT, 200 patients achieving engraftment were analyzed. Antibiotics were classified into carbapenem, quinolone, penicillin, cephem, and glycopeptide. Among 128 patients who developed acute GVHD, intestinal GVHD developed in 36 patients. Patients with intestinal GVHD received significantly longer administration of carbapenem and glycopeptide compared to those without it in periengraftment period. In multivariate analysis, use of carbapenem for greater than 7 days was associated with an increased risk of intestinal GVHD. However, use of antibiotics for greater than 7 days was not associated with poor overall survival and high nonrelapse mortality. Long use of carbapenem in periengraftment period may be a risk for intestinal GVHD. Prospective studies are required to validate our findings.

Re-infection of Toxoplasma gondii after HSCT presenting lymphadenopathy resembling recurrence of lymphoma.

Toxoplasma gondii (T. gondii) reactivation is one of the fatal complications after hematopoietic stem cell transplantation (HSCT); however, re-infection has not been reported. Here, we report a case of mycosis fungoides in which cervical lymphadenopathy developed after HSCT. Initially, recurrent lymphoma was suspected. However, biopsy of the lymph node showed typical histology of toxoplasmosis and serology showed re-infection of T. gondii. Toxoplasmosis needs to be differentiated for cases with lymphoadenopthy after HSCT.