Publications by authors named "Tetsuya Eto"

158 Publications

A phase I/II multicenter trial of HLA-haploidentical PBSCT with PTCY for aggressive adult T-cell leukemia/lymphoma.

Transplant Cell Ther 2021 Jul 15. Epub 2021 Jul 15.

Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.

Background: Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive hematologic malignancy with a very poor prognosis, and most patients with ATL are elderly. Although post-transplantation cyclophosphamide (PTCY) has yielded promising results in various diseases, available data are limited about its outcomes in ATL.

Objective: The aim of this study was to determine the safety and efficacy of reduced-intensity peripheral blood stem cell transplantation (PBSCT) from an HLA-haploidentical donor using PTCY as GVHD prophylaxis.

Study Design: This was a prospective, multicenter phase I/II study (UMIN000021783) conducted at 16 hospitals in Japan. The primary endpoint was the probability of survival with engraftment and without grade III-IV acute GVHD at day 60 after PBSCT. The expected probability of the primary endpoint was estimated to be 60%, and the threshold probability was set at 30% on the basis of previous studies. The conditioning regimen consisted of fludarabine (30 mg/m/day from day -7 to -2), melphalan (40 mg/m/day on days -3 and -2), and total body irradiation (2 Gy on day -1). GVHD prophylaxis consisted of tacrolimus starting at 0.02 mg/kg/day on day -1, PTCY (50 mg/kg/day on days +3 and +5), and mycophenolate mofetil 2000 mg/day starting on day +6.

Results: Eighteen ATL patients underwent PBSCT. The probability of patients who met the primary endpoint was 89% (95% confidence interval, 65%-99%). The cumulative incidences of grade II-IV acute GVHD, III-IV acute GVHD, and moderate-to-severe chronic GVHD were 39%, 11%, and 17%, respectively. The probabilities of overall survival were 83% at 1 year and 73% at 2 years. The cumulative incidences of non-relapse mortality and disease progression at 1 year were 11% and 28%, respectively.

Conclusion: HLA-haploidentical PBSCT with PTCY as GVHD prophylaxis is a valid option for patients with aggressive ATL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtct.2021.07.010DOI Listing
July 2021

Azacitidine for the treatment of patients with relapsed acute myeloid leukemia after allogeneic stem cell transplantation.

Leuk Lymphoma 2021 Jun 23:1-10. Epub 2021 Jun 23.

Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.

We retrospectively analyzed 38 patients with AML who received azacitidine (AZA) to treat disease relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with objective response (OR) ( = 20) after AZA had significantly higher 2-year overall survival (OS) (45.0% vs 5.6%;  = 0.004) than progressive disease. The 2-year OS was significantly higher in the retransplant group ( = 23) than in the nonretransplant group ( = 15) (34.8% vs 13.3%;  = 0.034). We analyzed 167 patients who underwent the second allo-HSCT to clarify the impact of pretransplant AZA after the second allo-HSCT. Patients in the AZA group ( = 21) had significantly higher 2-year disease-free survival (DFS) (32.7% vs 14.5%;  = 0.012) and OS (38.1% vs 17.5%;  = 0.044) than those in the SOC group ( = 146). Our data demonstrate that AZA is an effective and well-tolerated bridging therapy to the second allo-HSCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2021.1941937DOI Listing
June 2021

Differential Effect of Graft-versus-Host Disease on Survival in Acute Leukemia according to Donor Type.

Clin Cancer Res 2021 Jun 22. Epub 2021 Jun 22.

Division of Hematology, National Defense Medical College, Tokorozawa, Japan.

Purpose: The anti-leukemic activity of allogeneic hematopoietic cell transplantation (HCT) depends on both the intensity of conditioning regimen and the strength of the graft-versus-leukemia (GVL) effect. However, it is unclear whether the sensitivity of the GVL effects differs between donor type and graft source.

Experimental Design: We retrospectively evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on transplant outcomes for adults with acute leukemia ( = 6,548) between 2007 and 2017 using a Japanese database. In all analyses, we separately evaluated three distinct cohorts based on donor type [(8/8 allele-matched sibling donor, 8/8 allele-matched unrelated donor, and unrelated single-cord blood (UCB)].

Results: The multivariate analysis, in which the development of GVHD was treated as a time-dependent covariate, showed a reductive effect of grade I-II acute GVHD on treatment failure (defined as 1-leukemia-free survival; < 0.001), overall mortality (OM; < 0.001), relapse ( < 0.001), and non-relapse mortality (NRM; < 0.001) in patients receiving from UCB. A reductive effect of limited chronic GVHD on treatment failure ( < 0.001), OM ( < 0.001), and NRM ( < 0.001) was also shown in patients receiving from UCB. However, these effects were not always shown in patients receiving from other donors. The beneficial effects of mild acute and chronic GVHD after UCB transplantation on treatment failure were noted relatively in subgroups of patients with acute myelogenous leukemia and a non-remission status.

Conclusions: These data suggested that the development of mild GVHD could improve survival after UCB transplantation for acute leukemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-20-4856DOI Listing
June 2021

Personalized prediction of overall survival in patients with AML in non-complete remission undergoing allo-HCT.

Cancer Med 2021 Jul 16;10(13):4250-4268. Epub 2021 Jun 16.

Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Allogenic hematopoietic stem cell transplantation (allo-HCT) is the standard treatment for acute myeloid leukemia (AML) in non-complete remission (non-CR); however, the prognosis is inconsistent. This study aimed to develop and validate nomograms and a web application to predict the overall survival (OS) of patients with non-CR AML undergoing allo-HCT (cord blood transplantation [CBT], bone marrow transplantation [BMT], and peripheral blood stem cell transplantation [PBSCT]). Data from 3052 patients were analyzed to construct and validate the prognostic models. The common significant prognostic factors among patients undergoing allo-HCT were age, performance status, percentage of peripheral blasts, cytogenetic risk, chemotherapy response, and number of transplantations. The conditioning regimen was a significant prognostic factor only in patients undergoing CBT. Compared with cyclophosphamide/total body irradiation, a conditioning regimen of ≥3 drugs, including fludarabine, with CBT exhibited the lowest hazard ratio for mortality (0.384; 95% CI, 0.266-0.554; p < 0.0001). A conditioning regimen of ≥3 drugs with CBT also showed the best leukemia-free survival among all conditioning regimens. Based on the results of the multivariable analysis, we developed prognostic models showing adequate calibration and discrimination (the c-indices for CBT, BMT, and PBSCT were 0.648, 0.600, and 0.658, respectively). Our prognostic models can help in assessing individual risks and designing future clinical studies. Furthermore, our study indicates the effectiveness of multi-drug conditioning regimens in patients undergoing CBT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267144PMC
July 2021

Allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome in adolescent and young adult patients.

Bone Marrow Transplant 2021 May 15. Epub 2021 May 15.

Department of Hematology, Kanazawa University Hospital, Kanazawa, Japan.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curable treatment option for adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS). The study aim was to evaluate epidemiological data and identify prognostic factors for AYA patients with MDS undergoing allogeneic HSCT. Here, 645 patients were selected from patients enrolled in a multicenter prospective registry for HSCT from 2000 to 2015. The primary endpoint was 3-year overall survival (OS). Survival rates were estimated using the Kaplan-Meier method. Prognostic factors were identified using the multivariable Cox proportional hazards model. The 3-year OS was 71.2% (95% confidence interval [CI]: 67.4-74.6%). In multivariable analysis, active disease status (adjusted hazard ratio: 1.54, 95% CI: 1.09-2.18, p = 0.016), poor cytogenetic risk (1.62, 1.12-2.36, p = 0.011), poor performance status (2.01, 1.13-3.56, p = 0.016), human leukocyte antigen (HLA)-matched unrelated donors (2.23, 1.39-3.59, p < 0.001), HLA-mismatched unrelated donors (2.16, 1.09-4.28, p = 0.027), and cord blood transplantation (2.44, 1.43-4.17, p = 0.001) were significantly associated with poor 3-year OS. In conclusion, in AYA patients with MDS the 3-year OS following allogeneic HSCT was 71.2%. Active disease status, poor cytogenetic risk, poor performance status, and donor sources other than related donors were associated with poor 3-year OS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-021-01324-8DOI Listing
May 2021

Off-the-shelf bone marrow-derived mesenchymal stem cell treatment for acute graft-versus-host disease: real-world evidence.

Bone Marrow Transplant 2021 May 11. Epub 2021 May 11.

Department of Hematology, Hokkaido University Graduate School of Medical Science, Sapporo, Japan.

Temcell is a cryopreserved, human bone marrow-derived mesenchymal stem cell (MSC) product approved for the treatment of patients of all ages with acute graft-versus-host disease (GVHD). Initial experience with Temcell in a real-world setting from a cellular therapy registry in Japan is presented. A total of 381 consecutive patients were enrolled since its approval in 2016. The median cell number infused was 2.00 × 10/kg. The most common number of infusions was 8 in 100 patients. Of the 306 evaluable patients, the overall response rate (ORR) on day 28 after the start of MSC therapy was 56%. Of the 151 evaluable patients who received it as second-line therapy following first-line steroid therapy for classic acute GVHD, the ORR was 61%. Liver involvement of GVHD and ≥14 days from first-line steroid therapy to second-line MSC therapy was associated with a lower ORR. Day 28 ORR, patient age, GVHD grade, GVHD organ involvement, and a number of GVHD therapies before MSC therapy were associated with nonrelapse mortality. Overall survival at 6 months in 381 patients was 40%. This study suggests that Temcell is one of the treatment options for steroid-refractory acute GVHD until a new treatment with survival benefit is developed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-021-01304-yDOI Listing
May 2021

Severe acute graft-versus-host disease increases the incidence of blood stream infection and mortality after allogeneic hematopoietic cell transplantation: Japanese transplant registry study.

Bone Marrow Transplant 2021 Apr 19. Epub 2021 Apr 19.

Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.

This study aimed to clarify the risk factors and prognosis associated with blood stream infection (BSI) in allogeneic hematopoietic cell transplantation (allo-HCT), and the relationship between BSI and acute graft-versus-host disease (aGVHD). This retrospective analysis included 11,098 patients in the Japanese national transplant registry. A total of 2172 patients developed BSI after allo-HCT, with 2332 identified pathogens. The cumulative incidences of BSI were 15.5% at 30 days and 20.9% at 100 days after allo-HCT. In a multivariate analysis, severe (grade III-IV) aGVHD was associated with a higher risk of BSI (vs. grade 0-I aGVHD: hazard ratio [HR] 3.34 [95% confidence interval (CI), 2.85-3.92; P < 0.001]). In a multivariate analysis, severe aGVHD before BSI was associated with a higher risk of overall mortality after BSI (vs. grade 0-I aGVHD: HR 2.61 [95% CI 2.18-3.11; P < 0.001]). In addition, BSI (vs. no-BSI: HR 1.20 [95% CI, 1.12-1.29; P < 0.001]) and severe aGVHD (vs. grade 0-I aGVHD: HR 1.97 [95% CI, 1.83-2.12; P < 0.001]) were independent risk factors for overall mortality after allo-HCT. In the setting of allo-HCT, severe aGVHD was associated with increases in both BSI incidence and post-BSI overall mortality. Furthermore, BSI was an independent risk factor for overall mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-021-01291-0DOI Listing
April 2021

Prognostic Impact of the Fractionation of Total Body Irradiation for Patients with Acute Myeloid Leukemia Undergoing Myeloablative Allogeneic Hematopoietic Cell Transplantation.

Transplant Cell Ther 2021 02 13;27(2):185.e1-185.e6. Epub 2020 Dec 13.

Aichi Cancer Center, Nagoya, Japan. Electronic address:

Fractionated total body irradiation (TBI) at a total dose of 12 Gy is widely used for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT); however, there is limited information regarding the optimal number of fractions. To address this issue, Japanese nationwide transplantation registry data were analyzed. Because it was found that TBI was delivered almost exclusively in 4 (n = 1215, 30%) or 6 fractions (n = 2697, 67%), we focused on comparing 4- versus 6-fraction TBI. Compared to 6-fraction TBI, the 4-fraction version was associated with reduced risk of overall mortality (P = .002) and relapse (P = .018), while there was no difference in the risk of nonrelapse mortality (P = .422). The 4-fraction version did not aggravate acute graft-versus-host disease (GVHD), interstitial pneumonia, or sinusoidal obstruction syndrome of the liver. Chronic GVHD developed more frequently with the use of 4-fraction TBI, although the incidence of extensive chronic GVHD was similar. Subgroup analyses revealed that the 4-fraction version provided benefits for patients in non-complete remission (non-CR) but not for those in CR at transplantation. These findings suggest the advantage of 4-fraction over 6-fraction TBI for patients with AML undergoing allogeneic HCT in non-CR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtct.2020.10.018DOI Listing
February 2021

Clinical features and chromosomal/genetic aberration in adult acute lymphoblastic leukemia in Japan: results of Fukuoka Blood & Marrow Transplant Group Studies ALL MRD 2002 and 2008.

Int J Hematol 2021 Jun 16;113(6):815-822. Epub 2021 Mar 16.

Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.

Acute lymphoblastic leukemia (ALL) is a common neoplasm in children, but less frequent in adults. Since information on clinical features and genetics of adult ALL in Japan is limited, we analyzed 215 subjects aged 16-65 years with untreated ALL enrolled in the Fukuoka Blood & Marrow Transplant Group studies ALL MRD 2002 and 2008. The prevalence of ALL was bimodal, with the larger group aged 56-65 years. Immunophenotypic characterization showed B-lineage is more frequent than T-lineage ALL (78.6 vs 13.0%), with age-related differences. The proportion with BCR-ABL1 rearrangement increased progressively with age, up to 55.7% among subjects aged over 56-65 years. Rearrangements involving the KMT2A gene, ETV6-RUNX1, and TCF3-PBX1 were rare in this study cohort. The overall incidence of hyperdiploidy was only 1.7%, and there were no cases with hypodiploidy. Overall survival varied by age and cytogenetics. Older subjects and those with BCR-ABL1 tended to have inferior outcomes. In this epidemiological study of Japanese adult ALL, the majority of subjects had B-lineage ALL, the T-cell phenotype was most frequent in those aged 16-25, and BCR-ABL1 rearrangement was very common, with prevalence increasing with age. These types of adult ALL are potentially manageable with targeted therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-021-03116-8DOI Listing
June 2021

Efficacy of prophylactic letermovir for cytomegalovirus reactivation in hematopoietic cell transplantation: a multicenter real-world data.

Bone Marrow Transplant 2021 04 2;56(4):853-862. Epub 2020 Nov 2.

Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.

A novel anti-cytomegalovirus (CMV) agent, letermovir (LMV), could reportedly improve the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) recipients because of its high potential to prevent CMV reactivation. Therefore, 685 Japanese allo-HCT recipients, of whom ~80% had a high risk of CMV reactivation, were retrospectively analyzed to assess the impacts of prophylactic LMV on the incidence of clinically significant CMV (csCMV) infection as well as their transplant outcome. By comparing 114 patients who received LMV prophylaxis for a median 92 days to 571 patients without prophylaxis, we observed that prophylactic LMV could significantly (1) reduce the 180-day cumulative incidence of csCMV infection (44.7 vs. 72.4%, p < 0.001), (2) delay the median time until initiation of CMV antigenemia-guided preemptive therapy (90 vs. 36 days, p < 0.001), (3) shorten the duration of anti-CMV preemptive treatment (21 vs. 25 days, p = 0.006), and (4) improve the overall survival rate at 180 days after transplant (80.4 vs. 73.0%, p = 0.033) with a trend of lower non-relapse mortality (8.9 vs. 14.9%, p = 0.052). Our findings demonstrate that prophylactic LMV treatment is highly effective in preventing the development of csCMV infection and ultimately reduces transplant-related mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-020-01082-zDOI Listing
April 2021

Reduced dose of posttransplant cyclophosphamide in HLA-haploidentical peripheral blood stem cell transplantation.

Bone Marrow Transplant 2021 03 24;56(3):596-604. Epub 2020 Sep 24.

Department of Hematology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.

Posttransplant cyclophosphamide (PTCy:100 mg/kg) has been increasingly used in allogeneic hematopoietic stem cell transplantation, however, few studies compared different doses of PTCy. We conducted two consecutive prospective multicenter phase II studies to evaluate the safety and efficacy of 80 mg/kg of PTCy in 137 patients who underwent HLA-haploidentical peripheral blood stem cell transplantation (haploPBSCT) following reduced-intensity conditioning (RIC). GVHD prophylaxis consisted of PTCy at a dose of 40 mg/kg/day on days 3 and 4, tacrolimus, and mycophenolate mofetil. Neutrophil engraftment was achieved in 97% and 96% in the first and second studies, respectively. The incidences of grades II-IV acute GVHD, III-IV acute GVHD, all grade chronic GVHD, and moderate to severe chronic GVHD at 2 years were 26%, 5%, 35%, and 18% in the first study, and 23%, 1%, 28%, and 15% in the second study, respectively. Overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) at 2 years were 51%, 42%, and 18% in the first study, and 58%, 48%, and 16% in the second study, respectively. The rates of off-immunosuppressants in patients who survived without relapse at 2 years were 83 and 76%. Our results suggest that 80 mg/kg of PTCy is a valid option in haploPBSCT following RIC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-020-01065-0DOI Listing
March 2021

Effect of allogeneic HCT from unrelated donors in AML patients with intermediate- or poor-risk cytogenetics: a retrospective study from the Japanese Society for HCT.

Ann Hematol 2020 Dec 17;99(12):2927-2937. Epub 2020 Sep 17.

Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan.

This study aimed to analyze the factors associated with outcomes of bone marrow transplantation (UR-BMT) or cord blood stem cell transplantation from unrelated donors (UR-CBT). We assessed the time from diagnosis to transplantation among acute myeloid leukemia (AML) patients with intermediate- or poor-risk cytogenetics to identify the potential clinical efficacy of transplantation. We retrospectively analyzed 5331 patients who received UR-BMT or UR-CBT between 2008 and 2017. Patients were divided into four groups according to time from diagnosis to transplantation: (1) UR-BMT and > 5 months (n = 2353), (2) UR-BMT and ≤ 5 months (n = 379), (3) UR-CBT and > 5 months (n = 1494), and (4) UR-CBT and ≤ 5 months (n = 1106). There was no difference in overall survival (OS) for transplantation at ≤5 months and > 5 months in patients with first complete remission for both UR-BMT and UR-CBT, but OS in patients with primary induction failure (PIF) and transplantation at ≤ 5 months was significantly higher in the UR-CBT group compared with that at >5 months (P < 0.001). Multivariate Cox regression analysis also showed that transplantation at >5 months in patients with PIF was an independent predictor of poorer OS. Therefore, UR-CBT at ≤ 5 months after diagnosis is an alternative option for AML patients with PIF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-020-04261-6DOI Listing
December 2020

Use of unapproved or off-label drugs in Japan for the treatment of graft-versus-host disease and post-transplant viral infection.

Int J Hematol 2020 Dec 1;112(6):841-850. Epub 2020 Sep 1.

Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.

Many drugs are used for unapproved indications in Japan for post hematopoietic stem cell transplant (HCT) complications. To investigate unapproved or off-label drug usage for graft-versus-host disease (GVHD) and virus infections after allogeneic HCT, we analyzed the data of Japanese HCT registry. Between 2006 and 2017, 39,941 adults and children received HCT for a variety of disease and their transplant data were captured in the registry. Among them, 14,687 and 8914 patients receiving treatment for acute and/or chronic GVHD, 24,828 patients with cytomegalovirus (CMV) infection or receiving therapies for CMV, and 4943 who received treatment for other viral infections were included in the analyses of off-label or unapproved drugs. For GVHD, mycophenolate mofetil was the most frequently used off-label drug, followed by beclomethasone, infliximab, and etanercept. For viral infections other than CMV, foscarnet was the most frequently used off-label drug. Cidofovir, which is not approved for use in Japan, was mainly used for adenovirus infection. This study demonstrated that numerous off-label and unapproved drugs have been used as key drugs for GVHD and post-transplant viral infection, and the real world date in the transplant registry may serve as an important asset to regulatory purposes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-020-02972-0DOI Listing
December 2020

Allogeneic hematopoietic cell transplantation efficacy in patients with Philadelphia chromosome-positive acute myeloid leukemia in complete remission.

Bone Marrow Transplant 2021 01 31;56(1):232-242. Epub 2020 Jul 31.

Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan.

Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) confers a dismal prognosis when treated with chemotherapy alone. Data on allogeneic hematopoietic cell transplantation (allo-HCT) outcomes are limited. We retrospectively analyzed 4649 AML patients who received allo-HCT and were in complete remission. Outcomes of Ph+ AML (n = 30), intermediate-risk, and poor-risk AML patients were compared. The 3-year overall survival after allo-HCT was similar in intermediate-risk (62.7%; 95% CI: 61.0-64.3%) and Ph+ AML (73.3%; 95% CI: 51.5-86.4%) groups (P = 0.42); however, it differed significantly between the poor-risk (49.7%; 95% CI: 45.9-53.4%) and Ph+ AML (73.3%; 95% CI: 51.5-86.4%) groups (P = 0.049). Disease-free survival in Ph+ AML patients was comparable to that in intermediate-risk patients but better than that in poor-risk patients. Relapse rates were significantly lower in Ph+ AML patients than in other groups. Non-relapse mortality (NRM) rates were similar among groups. Multivariate analysis showed that Ph+ AML was not a significant predictor of poor prognosis in terms of overall survival, disease-free survival, relapse, and NRM. Our data showed better post-transplant outcomes for Ph+ AML patients than for those with poor-risk AML. Hence, allo-HCT could be a feasible treatment option for Ph+ AML patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-020-01011-0DOI Listing
January 2021

GVHD-free, relapse-free survival provides novel clues for optimizing allogeneic-HSCT for adult T-cell leukemia/lymphoma.

Bone Marrow Transplant 2021 01 14;56(1):155-166. Epub 2020 Jul 14.

Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.

The outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for adult T-cell leukemia/lymphoma (ATL) is still unsatisfactory. To illustrate the advantages and disadvantages of each donor source, we performed a nationwide retrospective study of graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) of patients with allo-HSCT-treated ATL. One-year GRFS did not significantly differ between patients who received related bone marrow transplantation (R-BMT; 26%, n = 117), related peripheral blood stem cell transplantation (R-PBSCT; 22%, n = 225), unrelated bone marrow transplantation (UR-BMT; 26%, n = 619), and cord blood transplantation (CBT; 21%, n = 359; p = 0.09). This was attributable to a low incidence of systemically-treated chronic GVHD after CBT (9% at 1 year) and reduced non-GVHD/relapse mortality after R-PBSCT (9% at 1 year). Among patients transplanted in complete remission (CR), 1-year overall survival after CBT (52%, n = 132) was not inferior to that after R-BMT (55%, n = 51), R-PBSCT (57%, n = 79), and UR-BMT (58%, n = 280; p = 0.15), and relapse rates were equivalent among the four sources (p = 0.19). Our results suggest that all donor sources are feasible for CR patients and that GRFS provides important clues toward optimizing allo-HSCT for ATL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-020-00996-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359445PMC
January 2021

Myeloablative intravenous busulfan-containing regimens for allo-HSCT in AML or MDS patients over 54 years old: combined results of three phase II studies.

Int J Hematol 2020 Oct 12;112(4):510-523. Epub 2020 Jul 12.

Department of Hematology, Karatsu Higashimatsuura Medical Association, Saga, Japan.

An optimal pretransplant conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in older adults has not been established. Three prospective multicenter phase II studies were conducted, in which 142 patients older than 54 years (median age, 61 years; range 55-70 years) with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) received a myeloablative dose of intravenous busulfan (ivBu, 12.8 mg/kg) along with fludarabine (180 mg/m) ± low dose total body irradiation for allo-HSCT between September 2009 and February 2013. A total of 103 AML and 39 MDS patients including 21 related bone marrow (BM) or peripheral blood (PB), 50 unrelated BM, and 71 unrelated cord blood (UCB) transplantation were enrolled. Grade 3 or greater toxicities were observed in 105 patients. Neutrophil engraftment was achieved in 70 out of the 71 related PB/BM or unrelated BM recipients, and 61 out of the 71 UCB recipients. The cumulative incidence rates of relapse and non-relapse mortality after 2 years were 24.0 and 24.1%, respectively. The overall and event-free survival rates at 2 years were 53.3 and 47.4%, respectively. The myeloablative dose of ivBu was well tolerated without increased toxicity-related mortality in older adults who underwent allo-HSCT with any donor source.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-020-02941-7DOI Listing
October 2020

Correction to: Measurable residual disease after the first consolidation predicts the outcomes of patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy.

Int J Hematol 2020 Sep;112(3):431-432

Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

In the original publication of the article, the "CNS involvement" in the last row under the column "Total N=50" has been published incorrectly. The correct Table 1 is given in this correction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-020-02932-8DOI Listing
September 2020

Low-dose anti-thymocyte globulin for GVHD prophylaxis in HLA-matched allogeneic peripheral blood stem cell transplantation.

Bone Marrow Transplant 2021 01 5;56(1):129-136. Epub 2020 Jul 5.

Department of Hematology, Hokkaido University Hospital, Sapporo, Japan.

Allogeneic peripheral blood stem cell transplantation (PBSCT) is associated with an increased risk of severe acute and chronic graft-versus-host disease (GVHD) compared to bone marrow transplantation. Anti-thymocyte globulin (ATG) can reduce severe acute and chronic GVHD in PBSCT; however, an optimal dose of ATG remains undefined. We conducted a multicenter phase II study to investigate safety and efficacy of low-dose ATG (a total of 2 mg/kg Thymoglobulin) in patients undergoing HLA-matched PBSCT after myeloablative conditioning. The primary endpoint was grades III-IV GVHD at 100 days. Seventy-seven patients were enrolled and 72 patients with a median age of 46.5 years were eligible for analysis. The primary endpoint, cumulative incidence of grades III-IV acute GVHD at 100 days was 1.4% (95% CI, 0.1-6.7%), which was greatly less than our pre-defined statistical threshold value (18.0%). The incidence of chronic GVHD at 1 year was also low (all-grade; 15.3%, moderate to severe; 5.6%). Non-relapse mortality, relapse, overall survival, disease-free survival, and GVHD-free, relapse-free survival at 1 year were 4.2%, 20.8%, 84.7%, 75.0%, and 69.4%, respectively. Low dose thymoglobulin is promising to reduce severe acute and chronic GVHD in HLA-matched PBSCT following myeloablative conditioning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-020-0985-3DOI Listing
January 2021

Measurable residual disease after the first consolidation predicts the outcomes of patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy.

Int J Hematol 2020 Sep 10;112(3):349-360. Epub 2020 Jun 10.

Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

We stratified patients with newly diagnosed acute promyelocytic leukemia (APL) according to a white blood cell (WBC) count of ≥ 3 × 10/L (high risk) or < 3 × 10/L (low risk) before administering risk-adapted chemotherapy in combination with all-trans retinoic acid (ATRA). In total, 27 low-risk and 23 high-risk patients were assigned to receive induction and three courses of consolidation with ATRA and anthracycline, followed by 2-year maintenance regimen. High-risk group additionally received cytarabine during 1st consolidation and another one-shot idarubicin treatment during 3rd consolidation. We prospectively monitored measurable residual disease (MRD) after induction and each consolidation. In the low-risk and high-risk groups, 5-year disease-free survival (DFS) rates were 86.5% and 81.2% (p = 0.862), and 5-year overall survival rates were 100% and 84.8% (p = 0.062), respectively. In the MRD-negative and MRD-positive groups, 5-year DFS rates were 91.7% and 78.4% (p = 0.402) and 84.7% and 60.0% (p = 0.102) after induction and 1st consolidation, respectively. Relapse rates were 8.3% and 13.3% (p = 0.570) and 9.0% and 40.0% (p = 0.076) after induction and 1st consolidation, respectively. Achieving MRD-negativity after 1st consolidation, rather than after induction, was a potential predictor of relapse and DFS in patients with APL treated with ATRA + chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-020-02911-zDOI Listing
September 2020

Outcome of stem cell transplantation for Waldenström's macroglobulinemia: analysis of the Japan Society for Hematopoietic Cell Transplantation (JSHCT) Lymphoma Working Group.

Ann Hematol 2020 Jul 18;99(7):1635-1642. Epub 2020 May 18.

Department of Oncology and Hematology, Shimane University Hospital, Izumo, Shimane, Japan.

The role of stem cell transplantation (SCT) for patients with Waldenström's macroglobulinemia (WM) remains undetermined. Therefore, we retrospectively evaluated the outcome of autologous and allogeneic SCT for patients with WM using the registry database of the Japan Society for Hematopoietic Cell Transplantation. Forty-six patients receiving autologous and 31 receiving allogeneic SCT were analyzed. The allogeneic SCT group included more patients with advanced disease status at transplant and received more lines of chemotherapy. The cumulative incidences of non-relapse mortality (NRM) at 1 year were 30.0% (95% CI, 14.7-46.9%) in the allogeneic SCT and 0% in the autologous SCT group. The estimated 3-year overall (OS) and progression-free (PFS) survival rates were 84.5% (95% CI, 66.0-93.4%) and 70.8% (95% CI, 53.0-82.9%) in the autologous SCT group, and 52.2% (95% CI, 32.5-68.6%) and 45.0% (95% CI, 26.3-62.0%) in the allogeneic SCT group. No patients died after the first 2 years following allogeneic SCT. In univariate analyses, disease status at SCT was significantly associated with PFS in autologous SCT, and with OS and PFS in allogeneic SCT. These results suggest that both autologous and allogeneic SCT have each potential role in WM. Allogeneic SCT is more curative for WM, but is associated with high NRM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-020-04078-3DOI Listing
July 2020

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

Biol Blood Marrow Transplant 2020 08 19;26(8):1543-1551. Epub 2020 Apr 19.

Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2020.04.004DOI Listing
August 2020

Tyrosine kinase inhibitors induce alternative spliced BCR-ABL variant via inhibition of RNA polymerase II on genomic BCR-ABL.

Cancer Sci 2020 Jul 14;111(7):2361-2373. Epub 2020 Jun 14.

Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.

To elucidate dynamic changes in native BCR-ABL and alternatively spliced tyrosine kinase inhibitor (TKI)-resistant but function-dead BCR-ABL variant, following commencement or discontinuation of TKI therapy, each transcript was serially quantified in patients with chronic myeloid leukemia (CML) by deep sequencing. Because both transcripts were amplified together using conventional PCR system for measuring International Scale (IS), deep sequencing method was used for quantifying such BCR-ABL variants. At the initial diagnosis, 7 of 9 patients presented a small fraction of cells possessing BCR-ABL , accounting for 0.8% of the total IS BCR-ABL, corresponding to actual BCR-ABL value of 1.1539% IS. TKI rapidly decreased native BCR-ABL but not BCR-ABL , leading to the initial increase in the proportion of BCR-ABL . Thereafter, both native BCR-ABL and BCR-ABL gradually decreased in the course of TKI treatment, whereas small populations positive for TKI-resistant BCR-ABL continued fluctuating at low levels, possibly underestimating the molecular response (MR). Following TKI discontinuation, sequencing analysis of 54 patients revealed a rapid relapse, apparently derived from native BCR-ABL clones. However, IS fluctuating at low levels around MR4.0 marked a predominant persistence of cells expressing function-dead BCR-ABL , suggesting that TKI resumption was unnecessary. We clarified the possible mechanism underlying mis-splicing BCR-ABL , occurring at the particular pseudo-splice site within intron8, which can be augmented by TKI treatment through inhibition of RNA polymerase II phosphorylation. No mutations were found in spliceosomal genes. Therefore, monitoring IS functional BCR-ABL extracting BCR-ABL would lead us to a correct evaluation of MR status, thus determining the adequate therapeutic intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.14424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385367PMC
July 2020

Effects of stem cell transplantation in patients with peripheral T-cell lymphoma not otherwise specified and angioimmunoblastic T-cell lymphoma.

Int J Hematol 2020 Jul 15;112(1):74-83. Epub 2020 Apr 15.

Department of Hematology and Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-Ku, Fukuoka, 810-8563, Japan.

The effects of stem cell transplantation (SCT) in patients with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL) remain controversial. We analyzed the feasibility of SCT and risk factors associated with outcomes of PTCL-NOS and AITL patients to identify the potential clinical efficacy of SCT. We retrospectively analyzed the data of PTCL-NOS (n = 83) and AITL (n = 112) patients who received autologous (n = 10 and 16, respectively) or allogeneic (n = 12 and 4, respectively) SCT, or no SCT (n = 61 and 92, respectively) between 2008 and 2018. All PTCL-NOS and AITL diagnoses were reconfirmed by an experienced hematopathologist. Median age at PTCL-NOS and AITL diagnoses in the SCT group was younger than that in the no SCT group. Significant risk factors for lower overall survival were intermediate-high and high-risk international prognostic indexes in PTCL-NOS patients (P = 0.0052), and a > 2 modified prognostic index for T-cell lymphoma (P = 0.0079) and no SCT (P = 0.028) in AITL patients. Autologous or allogeneic SCT compared with no SCT in AITL patients resulted in 3-year overall survival of 68.6% and 100% vs. 57.2% (P = 0.018). Strategies should be developed to improve selection of PTCL-NOS and AITL patients suitable for SCT and/or additional novel therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-020-02879-wDOI Listing
July 2020

Influence of HLA 1-3-locus mismatch and antithymocyte globulin administration in unrelated bone marrow transplantation.

Ann Hematol 2020 May 23;99(5):1099-1110. Epub 2020 Mar 23.

Division of Hematology, Jichi Medical University Saitama Medical Center, 1-847, Amanuma-cho, Omiya-ku, Saitama-city, Saitama, 330-8503, Japan.

For patients without an HLA-matched donor, an HLA-mismatched unrelated donor (MMUD) has been considered as an alternative donor in allogeneic hematopoietic cell transplantation (allo-HCT). We conducted a nationwide retrospective study to compare the transplant outcomes among 1-, 2-, and 3-locus (allele/antigen) mismatched unrelated donors (1MMUD n = 2044, 2MMUD n = 492, and 3MMUD n = 73) in allo-HCT and to assess the impact of antithymocyte globulin (ATG) in allo-HCT from 1-3MMUD. 2MMUD and 3MMUD were independent significant adverse factors for grade III-IV acute graft-versus-host disease (GVHD) (hazard ratio [HR] 1.72, p < 0.001 and HR 2.48, p < 0.001), non-relapse mortality (NRM) (HR 1.47, p < 0.001 and HR 2.00, p < 0.001), and overall survival (OS) (HR 1.21, p = 0.0066 and HR 1.60, p = 0.0015). Conversely, the use of ATG was an independent favorable factor for grade III-IV acute GVHD (HR 0.43, p < 0.001), NRM (HR 0.51, p < 0.001), and OS (HR 0.74, p = 0.0012). On the other hand, HLA compatibility and the use of ATG were not associated with a risk of relapse. An interaction test between the number of HLA mismatches and the use of ATG revealed that the effect of ATG on NRM and OS in the 2MMUD group was significantly less than that in the 1MMUD group (HR 1.53, p = 0.036 and HR 2.34, p = 0.0046). This study indicated that the number of HLA mismatches and the use of ATG were significantly associated with not only GVHD, but also NRM and OS. Whereas the use of ATG could improve transplant outcomes in allo-HCT from 1MMUD, its effectiveness with 2MMUD and 3MMUD was limited.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-020-03995-7DOI Listing
May 2020

Reduced-intensity stem cell transplantation for acute myeloid leukemia with fludarabine-based conditioning with intravenous busulfan versus melphalan.

Bone Marrow Transplant 2020 10 12;55(10):1955-1965. Epub 2020 Mar 12.

Department of Clinical Oncology and Hematology, The Jikei University School of Medicine, Tokyo, Japan.

Reduced-intensity conditioning (RIC) has been facilitating allogeneic hematopoietic cell transplantation (allo-HCT) for patients originally considered ineligible for HCT with myeloablative conditioning. Fludarabine (Flu) with reduced doses of busulfan (Bu) (Flu + Bu) and Flu with reduced doses of melphalan (Mel) (Flu + Mel) are widely used RIC regimens for acute myeloid leukemia (AML). A nationwide retrospective study comparing clinical outcomes of adult patients with AML receiving first allo-HCT after RIC between 2001 and 2010 was performed. Cumulative incidences of relapse were not significantly different among the Flu + ivBu-based (FBiv), Flu + poBu-based (FBpo), and Flu + Mel-based (FM) groups (p = 0.29). Non-relapse mortality (NRM) was significantly lower in patients receiving FBiv compared with FBpo (p = 0.003) and FM (p < 0.001). On multivariate analysis, there was no significant difference in overall survival, but FM was associated with a significantly lower risk of relapse (hazard ratio (HR) = 0.65, 95% confidence interval (CI): 0.50-0.85, p = 0.002), higher NRM (HR = 1.60, 95% CI: 1.10-2.33, p = 0.013) and better leukemia-free survival (HR = 0.77, 95% CI: 0.63-0.95, p = 0.015) compared with FBiv. These results suggest that Flu + Mel has a more intense disease control potential and Flu + ivBu is less toxic than the other. Both RIC regimens provide similar survival outcomes and are effective and useful regimens for patients with AML who received allo-HCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-020-0856-yDOI Listing
October 2020

Hematopoietic stem cell transplantation for pediatric acute promyelocytic leukemia in Japan.

Pediatr Blood Cancer 2020 05 21;67(5):e28181. Epub 2020 Jan 21.

Department of Pediatrics, Kyoto City Hospital, Kyoto, Japan.

Background: The number of hematopoietic stem cell transplantation (HSCT) procedures performed for pediatric acute promyelocytic leukemia (APL) has decreased in the all-trans retinoic acid (ATRA) era. Although HSCT is still widely adopted as part of salvage therapy for relapsed patients, there is no general consensus about the optimal transplant type (autologous [auto-HSCT] or allogeneic HSCT [allo-HSCT]).

Procedures: We retrospectively reviewed the clinical data of 95 childhood APL patients who underwent their first HSCT between 1990 and 2014. Of the 95 patients, 40 (42%), 41 (43%), and 3 (3%) underwent HSCT procedures after achieving their first complete remission (CR1), CR2, and CR3, respectively, and 11 (12%) underwent HSCT while in a non-CR state.

Results: The non-CR group exhibited significantly worse five-year overall survival (5yOS) and disease-free survival (5yDFS) (5yOS: 46%; 5yDFS: 46%) than the CR1 (5yOS: 80%; 5yDFS: 78%) and CR2 + CR3 groups (5yOS: 81%; 5yDFS: 76%) (P = 0.013 and P < 0.01, respectively). Of the patients treated in CR2, no significant differences in 5yOS or the five-year cumulative incidence of relapse (5yRI) were detected between the auto-HSCT and allo-HSCT groups (5yOS: 85%, vs 78%, P = 0.648; 5yRI: 9%, vs 11%, P = 0.828). Among the patients who underwent allo-HSCT in CR2, those with matched sibling donors displayed a significantly higher 5yRI (33%) than those with other types of donors (0%, P = 0.015).

Conclusions: Even after relapsing, childhood APL can be cured with HSCT if CR is achieved. These findings demonstrate that achieving CR followed by HSCT is the preferred strategy for treating children with relapsed or refractory APL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28181DOI Listing
May 2020

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

Hematol Oncol 2020 Apr 3;38(2):146-152. Epub 2020 Feb 3.

Department of Oncology and Hematology, Shimane University Hospital, Izumo, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hon.2714DOI Listing
April 2020

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

Am J Hematol 2020 04 2;95(4):343-353. Epub 2020 Jan 2.

Division of Hematology, National Defense Medical College, Tokorozawa, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.25705DOI Listing
April 2020
-->