[Evaluation of the correlation between JAK2V617F allele burden by Quenching Probe-Tm method and allele-specific quantitative PCR method].

The JAK2V617F mutation is a driver mutation of myeloproliferative neoplasms (MPNs). V617F allele burden is considered a risk factor for complications associated with MPNs and is a predictor of prognosis. In Japan, V617F allele burden has been measured in laboratory settings using the i-densyTM IS-5320 genetic analyzer with the quenching probe-Tm (QP-Tm) method. However, since 2020, allele-specific quantitative PCR (AS-qPCR) is being performed in clinical settings for measuring V617F allele burden. To investigate the clinical usefulness of the QP-Tm method in patients with MPNs, we evaluated the V617F allele burden measured by both the methods. A good correlation was observed between the V617F allele burden determined using QP-Tm and that determined using AS-qPCR (P<0.001, rs=0.952). The median mutant allele burden, as determined using the QP-Tm method, was significantly higher in patients with polycythemia vera than in those with essential thrombocythemia. The results of this study suggested that the QP-Tm method will continue to be useful clinical ancillary test for measuring V617F allele burden.

Single cord blood transplantation for acute myeloid leukemia patients aged 60 years or older: a retrospective study in Japan.

The availability of alternative donor sources could allow elderly patients to receive allogeneic hematopoietic cell transplantation (HCT). We retrospectively evaluated the outcomes of single-unit cord blood transplantation (CBT) in 1577 patients aged ≥60 years with acute myeloid leukemia (AML) in Japan between 2002 and 2017. In total, 990 (63%) patients were not in complete remission (CR) at the time of CBT. A myeloablative conditioning regimen (52%) and calcineurin inhibitor (CI) + mycophenolate mofetil (MMF)-based graft-versus-host disease (GVHD) prophylaxis (45%) were more commonly used. With a median follow-up for survivors of 31 months, the probability of overall survival and the cumulative incidence of leukemia-related mortality at 3 years was 31% and 29%, respectively. The cumulative incidence of non-relapse mortality (NRM) at 100 days and 3 years were 24% and 41%, respectively. The cumulative incidences of grade II-IV and grade III-IV acute GVHD at 100 days and extensive chronic GVHD at 2 years were 44%, 16%, and 14%, respectively. The cumulative incidence of neutrophil engraftment was 80% at 42 days. Results of multivariate analysis indicated that the following factors were significantly associated with higher overall mortality: performance status ≥1, hematopoietic cell transplantation-specific comorbidity index ≥3, adverse cytogenetics, extramedullary disease at diagnosis, and non-CR status at CBT. By contrast, female sex, HLA disparities ≥2, mycophenolate mofetil-based GVHD prophylaxis, and recent CBT were significantly associated with lower overall mortality. In conclusion, single CBT offers a curative option for AML patients aged ≥60 years with careful patient selection.

Outcome and Risk Factors for Therapy-Related Myeloid Neoplasms Treated with Allogeneic Stem Cell Transplantation in Japan.

This study aimed to investigate allogeneic hematopoietic cell transplantation (HCT) outcomes and risk factors in adult patients with therapy-related myeloid neoplasm (t-MN) using Japanese registry data. Between 2002 and 2012, a total 12,169 adult patients underwent HCT for acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML). Of these, 565 with t-MN were identified. The median patient age was 54 years (range, 16 to 80 years). Three hundred and ninety-eight patients had AML, 154 had MDS, and 13 had CMML. Lymphoma and breast cancer were the major previous malignancies. Favorable karyotypes were detected in 84 patients, and poor karyotypes were identified in 235. Two-thirds (66%) of the patients were in nonremission at HCT. Overall survival at 3 years in patients with t-MN was 31% (95% confidence interval [CI], 27% to 35%), equivalent to that in those with secondary MN (32%; 95% CI, 30% to 34%), and 44% in the de novo cohort (95% CI, 43% to 45%). The cumulative incidence of relapse and nonrelapse mortality at 3 years was 40% and 33%, respectively. The outcomes of HCT for t-MN in Japan were comparable to those in large-scale studies in Europe and the United States.

Impact of Homozygous Conserved Extended HLA Haplotype on Single Cord Blood Transplantation: Lessons for Induced Pluripotent Stem Cell Banking and Transplantation in Allogeneic Settings.

Induced pluripotent stem cells (iPSCs) have been applied to clinical regenerative cell therapy. Recently, an iPSC banking system to collect HLA haplotype (HP) homozygous (homo) cells for iPSC transplantation in allogeneic settings was proposed, and tissue transplantation generated from iPSC through banking has just began. We analyzed 5017 single cord blood transplantation (CBT) pairs with HLA-A, -B, -C, -DRB1 allele typing data and found 39 donor HLA homo donor to patient HLA heterozygous (hetero) pairs. Of note, all 39 HLA homo to hetero pairs engrafted neutrophils, except 1 early death pair, and all 30 assessable pairs engrafted platelets. Acute graft-versus-host disease (GVHD) grades II to IV and grades III to IV occurred in 17 and 3 of 38 assessable pairs, respectively. Competing risk regression analysis revealed a favorable risk of neutrophil engraftment and higher risk of acute GVHD compared with HLA-matched CBTs. Thirty-seven of 39 homo to hetero pairs had conserved extended HLA HPs (HP-1, n = 18; HP-2, n = 8; HP-3, n = 7; HP-4, n = 4; HP-5, n = 1) that were ethnicity-specific, and at least 1 of 2 patient HLA-A, -B, -C, and -DRB1 alleles in each locus were invariably shared with the same donor HP in 35 pairs. These findings confirmed our preliminary results with 6 HLA homo CBTs, and a trend of high incidence of acute GVHD was newly observed. Importantly, they imply the possibility that HLA-homo iPSC transplantation provides favorable engraftment and accordingly imply the merit of banking iPSC with homozygous major conserved extended HLA HPs.

Effects of Haplotype Matching on Outcomes after Adult Single-Cord Blood Transplantation.

It remains unclear whether the HLA haplotype of unrelated cord blood (UCB) should be matched to that of the patient in single UCB transplantation. Thus, using data from a Japanese registry, we analyzed the effect of haplotype matching on outcomes. Patients with hematologic diseases aged 16 years or older who had undergone their first transplant were included (N = 1347). The effects of haplotype matching and high-frequency HLA haplotype on outcomes were analyzed. Median patient age was 55 years. The cumulative incidences of neutrophil engraftment among groups with 0, 1, and 2 HLA haplotype matches were 79%, 82%, and 88%, respectively (P = .008). In a multivariate analysis, the group with 0 haplotype matches was marginally associated with worse neutrophil engraftment (P = .087) and significantly associated with platelet engraftment (P = .044) compared with the group with 1 haplotype match. Two-haplotype matches were associated with a higher risk of relapse. In the group with 1 haplotype match, the top 3 shared haplotypes were "A*24:02-B*52:01-C*12:02-DRB1*15:02" (HP-P1), "A*33:03-B*44:03-C*14:03-DRB1*13:02" (HP-P2), and "A*24:02-B*07:02-C*07:02-DRB1*01:01" (HP-P3). The presence of HP-P2 but not HP-P1 or HP-P3 was associated with a decreased risk of grades II to IV acute graft-versus-host disease (hazard ratio, .56; P = .001) but an increased risk of relapse (hazard ratio, 1.35; P = .045). HLA haplotype matching might be considered to improve engraftment. Two-haplotype matches should be avoided if the relapse risk is high. The haplotype itself may have an effect on the risk of acute graft-versus-host disease and relapse.

The impacts of BCR-ABL1 mutations in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent allogeneic hematopoietic cell transplantation.

The prognostic impacts of BCR-ABL1 fusion gene mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remain unknown. Using data from a nationwide Japanese registry, we have evaluated the prognostic impact of BCR-ABL1 mutations prior to the first allogeneic hematopoietic cell transplantation (HCT). The cohort included 289 patients with a median of 48 years of age (range: 16-70). Point mutations were detected in 110 patients. Of these, 90 (82%) harbored T315I mutations, while 20 had other mutations. With a median follow-up period of 29 months (range: 1-125), outcomes after 2 years were worse with mutations than without (overall survival [OS]: 34% vs 68%, p < 0.001; relapse rate [RR]: 48% vs 18%, p < 0.001), particularly with the presence of the T315I mutation (OS: 29% vs 68%, p < 0.001; RR: 54% vs 18%, p < 0.001). OS was significantly worse in the T315I group even among the cohort with hematological (p < 0.001) or molecular complete remission (p = 0.025) as compared to the no mutation group. Multivariate analysis determined the prognostic impact of the T315I mutation (OS: hazard ratio [HR] = 2.19, 95% confidence interval [CI]: 1.5-3.3, p < 0.001; RR: HR = 2.51, 95% CI: 1.5-4.2, p < 0.001). This study is the first to report on the prognostic significance of BCR-ABL1 mutations in Ph + ALL.

Improvement of early mortality in single-unit cord blood transplantation for Japanese adults from 1998 to 2017.

The major limitation of cord blood transplantation (CBT) for adults remains the delayed hematopoietic recovery and higher incidence of graft failure, which result in a higher risk of early mortality in CBT. We evaluated early overall survival (OS), non-relapse mortality (NRM), neutrophil engraftment, acute graft-vs-host disease, and cause of early death among 9678 adult patients who received single-unit CBT in Japan between 1998 and 2017. The probability of OS at 100 days was 64.4%, 71.7%, and 78.9% for the periods 1998 to 2007, 2008 to 2012, and 2013 to 2017, respectively (P < .001). The cumulative incidences of NRM at 100 days during the same period were 28.3%, 20.8%, and 14.6%, respectively (P < .001). The cumulative incidences of neutrophil engraftment were also improved during the same period (P < .001). The most common cause of death within 100 days after CBT was bacterial infection in 1998 to 2007 and primary disease in the latter two time periods. Across the three time periods, the proportions of deaths from bacterial and fungal infection, graft failure, hemorrhage, sinusoidal obstructive syndrome, and organ failure decreased in a stepwise fashion. Landmark analysis of OS and NRM after 100 days showed that OS did not change over time in the multivariate analysis. Our registry-based data demonstrated a significant improvement of early OS after CBT for adults over the past 20 years. The landmark analysis suggested that improvement of early mortality could lead to an improvement of long-term OS after CBT.

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.

A prospective multicenter phase II study of intrabone marrow transplantation of unwashed cord blood using reduced-intensity conditioning.

Cord blood transplantation (CBT) is associated with delayed hematopoietic recovery and graft failure. To overcome these problems, we conducted a prospective, multicenter phase II study of intrabone marrow transplantation in which patients received reduced-intensity conditioning without anti-thymocyte globulin (ATG). The primary endpoint was the probability of full donor engraftment. Forty patients with hematologic malignancies were enrolled. Cord blood (CB) cells were injected without washing into 4 iliac bone sites (2 at each hemipelvis), at which approximately 6 mL of CB was administered at one site with local anesthesia. Full donor engraftment rate was 86.8%. The cumulative incidence of neutrophil and platelet engraftment was 86.4% and 85.5%, respectively. The median time to neutrophil (>0.5 × 109 /L) and platelet (2.0 × 109 /L) recovery was 17.5 and 44 days, respectively. The probability of severe acute graft-vs-host disease (GVHD) was 47.5%. The cumulative incidence of extensive chronic GVHD was 3.0%. The probability of relapse and non-relapse mortality was 30.4% and 28.0%, respectively. The survival rate at 3 years was 45.6%, although most patients were at an advanced stage. These results suggest that our intrabone marrow-CBT procedure without using ATG improves hematopoietic recovery and decreases the incidence of chronic GVHD, but does not decrease the incidence of acute GVHD.

Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older.

Older recipient and donor age were associated with higher incidences of severe graft-versus-host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome aged 50 years or older who underwent MSD bone marrow transplantation (BMT) (n = 319), MSD peripheral blood stem cell transplantation (PBSCT) (n = 462), or unrelated CBT (n = 1,310) between 2007 and 2012. Median age of MSD was 56 (range, 38-74) years. Compared with CBT, the risk of developing extensive chronic GVHD was higher after BMT (hazard ratio [HR], 2.00; P = 0.001) or PBSCT (HR, 2.38; P < 0.001), and transplant-related mortality was lower after BMT (HR, 0.61; P < 0.001) or PBSCT (HR, 0.63; P < 0.001). Relapse rates were not significant difference between three groups. Although overall mortality was lower after BMT (HR, 0.67; P < 0.001) or PBSCT (HR, 0.75; P = 0.002) compared with CBT, the rates of a composite endpoint of GVHD-free, relapse-free survival (GRFS) were not significant difference between three groups. These data showed that MSDs remain the best donor source for older patients, but CBT led to similar GRFS to BMT and PBSCT.

[Correlation between serum L-carnitine concentration and neutrophil engraftment in patients treated with cord blood transplantation].

In cord blood transplantation (CBT), the amount of time elapsing until hematological engraftment has effects on the transplantation results. Carnitine deficiency has been reported to cause erythropoietin refractory anemia in chronic hemodialysis patients and thrombocytopenia or leukopenia of cirrhosis, and carnitine supplementation can improve hematopoiesis in patients with hepatic or renal failure. Patients who receive CBT may suffer from carnitine deficiency, but no studies have investigated the carnitine status of such patients. Herein, we determined the concentration of free carnitine (FC) and investigated the correlation between FC and engraftment in patients who received CBT. Twenty-three patients who received CBT at our hospital during the period from April 2013 to January 2015 were enrolled in this study. One patient was excluded because of graft failure, such that 22 patients were ultimately evaluable. FC concentrations of the patients were sequentially monitored at 4 time points (before conditioning therapy, day 0, day 7, and day 14), basic laboratory data were collected, and their correlations with engraftment were analyzed. FC concentrations of the patients were generally low (before conditioning therapy: 33.1, day 0: 43.2, day 7: 38.3, and day 14: 37.8 µmol/l). Significant inverse correlations were observed between FC concentrations and the number of days required for neutrophil engraftment on day 0 and day 14 (before conditioning therapy: P=0.15, r=-0.33, day 0: P=0.04, r=-0.43, day 7: P=0.30, r=-0.23, and day 14: P=0.01, r=-0.55). These results suggest carnitine to be an important nutrient that promotes hematopoietic recovery after CBT.

Impact of HLA disparity in the graft-versus-host direction on engraftment in adult patients receiving reduced-intensity cord blood transplantation.

Delayed engraftment or graft failure is one of the major complications after cord blood transplantation (CBT). To investigate factors impacting engraftment, we conducted a retrospective analysis of adult patients who underwent reduced-intensity CBT at our institute, in which preparative regimens mainly consisted of fludarabine, melphalan, and total body irradiation with graft-versus-host (GVH) disease prophylaxis using single calcineurin inhibitors. Among 152 evaluable patients, the cumulative incidence of neutrophil engraftment was 89%. High total nucleated cell and CD34(+) cell dose were associated with the faster speed and higher probability of engraftment. In addition, the degree of human leukocyte antigen (HLA) mismatch in the GVH direction was inversely associated with engraftment kinetics, whereas no statistically significant association was observed with the degree of HLA mismatch in the host-versus-graft direction. Similarly, the number of HLA class I antigens mismatched in the GVH direction, but not in the host-versus-graft direction, showed a negative correlation with engraftment kinetics. HLA disparity did not have significant impact on the development of GVH disease or survival. This result indicates the significant role of HLA disparity in the GVH direction in the successful engraftment, raising the novel mechanism responsible for graft failure in CBT.

Successful treatment with ABL tyrosine kinase inhibitor for patients with acute myeloid leukemia with BCR-ABL1.

Acute myeloid leukemia (AML) with BCR-ABL1 is rare and has a poor prognosis with conventional chemotherapy or ABL tyrosine kinase inhibitors (TKIs) alone. We reported a case of AML with BCR-ABL1 patient who was successfully treated with dasatinib alone; additionally, we previously reported another case of long-term remission maintained with imatinib monotherapy. These results suggested that a treatment with a novel and significantly potent TKI may be effective in AML with BCR-ABL1 patients with low tumor burden and without additional chromosome aberrations and ABL kinase domain mutations.

Comparison of immunosuppressant regimens in salvage cord blood transplantation for graft failure after allogeneic hematopoietic stem cell transplantation.

Graft failure (GF) is a life-threatening complication after allogeneic stem cell transplantation. Although salvage cord blood transplantation (CBT) is a curative therapy for GF, the optimal immunosuppression after salvage CBT remains unknown. Using nationwide registration data, we compared the transplant outcomes of patients who developed GF and underwent salvage CBT using immunosuppressants, including calcineurin (CNI) alone (n = 177); CNI plus methotrexate (CNI+MTX, n = 150); and CNI plus mycophenolate mofetil (CNI+MMF, n = 161). The CNI+MMF group, in comparison with the CNI+MTX and CNI alone groups, demonstrated better neutrophil recovery at 30 days (62.7 vs. 42.7 vs. 53.1%, P < 0.001); better overall survival (OS) at 12 months (48.4 vs. 33.5 vs. 28.3%, P < 0.001); and lower non-relapse mortality (NRM) at 12 months (35.2 vs. 53.9 vs. 56.5%, P < 0.001). On multivariate analysis, CNI+MMF had the best neutrophil recovery (hazard ratio (HR), 1.71; P < 0.001) and OS (HR, 0.64; P = 0.002) and the lowest NRM (HR, 0.53; P < 0.001). Hemorrhage was relatively less frequent in the CNI+MMF group. CNI+MMF can be a promising immunosuppressant regimen after salvage CBT for GF, with better engraftment and survival outcomes, compared with CNI alone and CNI+MTX.

Jumping translocations of 1q in donor cell-derived myelodysplastic syndrome after cord blood transplantation: Case report and review of the literature.

Donor cell-derived leukemia and myelodysplastic syndrome (DCL) is a rare complication in patients after allogenic stem cell transplantation (SCT). Since 1971, numerous cases of DCL have been reported, but the detailed mechanisms of DCL are still unclear. A patient with jumping translocations (JTs) of 1q in umbilical cord blood donor cell-derived myelodysplastic syndrome (MDS), which likely occurred due to genetic alterations of TET2 and ASXL1 after cord blood transplantation (CBT), was examined in this study. Previously reported DCL cases after CBT that focused on the cytogenetic and molecular characteristics of these patients and patient outcome were reviewed. A total of 30 cases of DCL after CBT were identified between 2005 and 2018. The median time from CBT to the development of DCL was 16 months. The number of patients with DCL who were diagnosed with acute myeloid leukemia (AML) and MDS was 19 and 8, respectively. JTs were frequently observed in 5 of 27 DCL patients who had cytogenetic abnormalities, including our patient. Molecular abnormalities were described in 7 of the cases, and the most frequent abnormality was an NPM1 mutation. Other gene mutations that were usually found in de novo MDS or AML were observed in JT-DCL after CBT. From these results, chromosomal abnormalities such as JTs that occur subsequent to genetic alterations were seemed an important mechanisms underlying DCL onset in patients after CBT. Further molecular analyses regarding the genetic alterations of JTs are required to understand the pathogenesis of umbilical cord blood-derived JT-DCL.

High incidence of haemophagocytic syndrome following umbilical cord blood transplantation for adults.

Umbilical cord blood transplantation (CBT) is widely accepted, but one critical issue for adult patients is a low engraftment rate, of which one cause is haemophagocytic syndrome (HPS). We aimed to identify the contribution of HPS to engraftment failure after CBT, following preparative regimens containing fludarabine phosphate, in 119 patients (median age, 55 years; range; 17-69 years) with haematological diseases. Graft-versus-host disease prophylaxis comprised continuous infusion of a calcineurin inhibitor with or without mycophenolate mofetil. Of the 119 patients, 20 developed HPS within a median of 15 d (cumulative incidence; 16.8%) and 17 of them did so before engraftment. Donor-dominant chimaerism was confirmed in 16 of 18 evaluable patients with HPS. Despite aggressive interventions including corticosteroid, ciclosporin, high-dose immunoglobulin and/or etoposide, engraftment failed in 14 of 18 patients. Of these 14 patients, four received second rescue transplantation and all resulted in successful engraftment. Overall survival rates significantly differed between patients with and without HPS (15.0% vs. 35.4%; P < 0.01). Univariate and multivariate analysis identified having fewer infused CD34(+) cells as a significant risk factor for the development of HPS (P = 0.01 and 0.006, respectively). We concluded that engraftment failure closely correlated with HPS in our cohort, which negatively impacted overall survival after CBT.

Transformation from follicular lymphoma to high-grade B-cell lymphoma/leukemia with additional t(2;8)(p12;q24), with inverse expressions of c-MYC and BCL-2, and light-chain switch.

Transformation from follicular lymphoma (FL) to high-grade B-cell lymphoma/leukemia (BLL) has been reported in patients with additional translocations involving the c-MYC gene. The previously reported cases were related to t(8;14) and t(8;22) but not to t(2;8). Herein is reported an FL that terminated in BLL following additional t(2;8). In accordance with previous reports, increased expression of c-MYC was observed in the present case but, interestingly, BCL-2 expression was inversely decreased after the transformation. In addition, the cell-surface immunoglobulin light-chain of lymphoma cells was initially kappa type and was then gradually replaced with the lambda type after transformation. Downregulation of BCL-2 and light-chain switch have rarely been reported in previous cases of FL transformation involving c-MYC, suggesting that additional t(2;8) translocation may play a role in these events.

[Development of treatment adherence by jellification of itraconazole oral solution].

There have been some reports on the efficacy and tolerability of itraconazole (ITCZ) as prophylaxis for fungal infection after HSCT, and guidelines recommend itraconazole as a standard drug for prophylaxis of fungal infection in HSCT patients. However, it is not uncommon for patients undergoing HSCT to develop anorexia and taste disturbance. There are some cases where the bitter taste of ITCZ oral solution leads to interruption of administration because the patient refuses to take this medicine. Therefore, we investigated the clinical utility and influence on continuing treatment adherence by jellification of ITCZ. Compared with ITCZ oral solution, jellified ITCZ was extremely easy for most patients to take, and it was suggested that jellified ITCZ can make it easier for patients to continue treatment if they have difficulty with administration because of the bitter taste of ITCZ oral solution. Furthermore, it was confirmed that the plasma concentration of ITCZ was suitable for prophylaxis even with jellified ITCZ. This also suggested that the efficacy of ITCZ would be maintained by using jellified formation. For long-term antifungal therapy in patients with a high risk of fungal infection such as those having HSCT, it is very important for successful prophylaxis to maintain good adherence.

Successful Cord Blood Transplantation in a Werner Syndrome Patient with High-risk Myelodysplastic Syndrome.

Werner syndrome (WS) confers a high risk of the development of neoplasias, including hematological malignancies, and curative treatment for these malignancies is difficult to achieve. A 44-year-old man with myelodysplastic syndrome was admitted to our hospital. He was diagnosed with mutation-proven WS. He underwent cord blood transplantation (CBT) following fludarabine, busulfan, and melphalan administration. A chimerism analysis of his marrow blood on day 62 showed a donor pattern >95%, which confirmed engraftment. The patient lived for 15 months while maintaining remission of MDS without treatment-related toxicity. Our case shows that CBT can be a treatment modality for WS patients with hematological malignancies.