Publications by authors named "Kazuhiro Ikegame"

120 Publications

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

Impact of the use of hydroxyethyl starch in granulocyte apheresis using Spectra Optia.

Transfus Med 2021 Jun 6. Epub 2021 Jun 6.

Department of Transfusion Medicine and Cellular Therapy, Hyogo College of Medicine Hospital, Nishinomiya, Japan.

Objectives: To determine the impact of the use of hydroxyethyl starch (HES) in granulocyte apheresis using Spectra Optia.

Background: Granulocyte transfusion (GT) is a therapeutic option for neutropenic patients with severe bacterial or fungal infections. Recent studies in emergency medicine have shown the potential risk of using HES, which is routinely used in granulocyte apheresis to increase yield by sedimenting red blood cells. We hypothesized that the use of a newer device (Spectra Optia) would spare the need for HES.

Methods: We retrospectively compared granulocyte apheresis with HES (HES group, n = 89) and without HES (non-HES group, n = 36) using Spectra Optia.

Results: The granulocyte yield was significantly higher in the HES group (7.3 × 10 vs. 2.0 × 10, p < 0.01) and was attributed to the difference in collection efficiency (36% vs. 7.7%, p < 0.01). The absolute neutrophil count on the following morning of GT was significantly higher in the HES group than in the non-HES group (2460/μl vs. 505/μl, p < 0.01). There were no significant differences in the occurrence of adverse events between the HES and non-HES groups. The renal function was unchanged in both groups after apheresis.

Conclusions: We demonstrated that the advantage of using HES remained unchanged in granulocyte apheresis using Spectra Optia.
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http://dx.doi.org/10.1111/tme.12795DOI Listing
June 2021

The Combination of Interferon-Alpha and Ponatinib Enables Faster and Deeper Molecular Responses in Patient with De Novo Blast Crisis of CML: Interferon-Alpha May Return as a CML Treatment.

Case Rep Hematol 2021 3;2021:5518727. Epub 2021 May 3.

Department of Hematology Nephrology and Rheumatology, Akita University, 1-1 Hondo 1-Chome, Akita 010-8543, Japan.

In the era of tyrosine kinase inhibitor (TKI) treatment, its effectiveness in treating chronic myelogenous leukemia (CML) has been improved, ensuring the same prognosis as that of healthy people of the same age. However, there are some patients with de novo blast crisis that undergoes acute conversion from the time of diagnosis and does not respond to TKI treatment, especially in the older patients. Here, we present a case of an older patient with de novo lymphoid crisis who was first treated with a combination of TKI and chemotherapy, but it was difficult to maintain a durable deep molecular response (DMR). After he achieved major molecular response (MMR) or less, it was possible to suppress IS% to DMR by performing a combined treatment with interferon- (IFN-) and ponatinib. It is considered that DMR can be maintained by the combination of the two-way action of IFN-, that is, the transfer of dormant CML stem cells to the cellcycle and the activation of a specific immune response to CML cells. This clinical result suggests the possibility of the re-emergence of IFN-, which has been used a therapeutic drug in the past.
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http://dx.doi.org/10.1155/2021/5518727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112961PMC
May 2021

Allogeneic hematopoietic stem cell transplantation for adult patients with B-cell acute lymphoblastic leukemia with high hyperdiploidy: a retrospective nationwide study.

Leuk Lymphoma 2021 May 12:1-7. Epub 2021 May 12.

Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan.

We compared the transplant outcomes of adult patients with B-cell acute lymphoblastic leukemia characterized by high hyperdiploidy (HeH; 51-65 chromosomes) ( = 29) and those with a normal karyotype ( = 87) by propensity score-matched analysis. There were no significant differences among groups in 3-year probabilities of overall survival (OS, 63.5% vs. 55.3%,  = .553), cumulative relapse incidence (28.6% vs. 28.7%,  = .982), and non-relapse mortality (10.9% vs. 21.4%,  = .303). Three-year OS was significantly worse in HeH patients with third or later complete remission (CR) or non-CR compared with those in first CR (19.0% vs. 69.9%,  = .010). Frequently gained chromosomes +21 (75.9%), +4 (69.0%), +6 (69.0%), +10 (69.0%), and +1 (69.0%) had no significant prognostic impact on the OS of patients with HeH in multivariate analyses. Patients with HeH who may benefit from allogeneic hematopoietic stem cell transplantation should be further analyzed.
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http://dx.doi.org/10.1080/10428194.2021.1924374DOI 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.
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http://dx.doi.org/10.1038/s41409-021-01304-yDOI Listing
May 2021

Relationship Between Corticosteroid Dose and Muscle Oxygen Consumption in Recipients of Hematopoietic Stem-Cell Transplantation.

Adv Exp Med Biol 2021 ;1269:87-93

Department of Physical Medicine and Rehabilitation, Hyogo College of Medicine, Nishinomiya, Japan.

Introduction: After hematopoietic stem-cell transplantation (HSCT), patients exhibit decreased muscle strength and muscle oxygen consumption. Furthermore, total corticosteroid dose affects the reduction in muscle strength after HSCT. However, to date, no studies have investigated the relationship between corticosteroid dose and muscle oxygen consumption and saturation in these patients. The purpose of this study was to investigate the relationship between steroid dose and deoxyhemoglobin (ΔHHb) and muscle oxyhemoglobin saturation (ΔSmO) in patients undergoing HSCT.

Methods: This study included 17 men with hematologic disease who underwent allogeneic HSCT. We evaluated ankle dorsiflexor muscle force, ΔHHb, and ΔSmO in skeletal muscles by near-infrared spectroscopy (NIRS) in patients before and after HSCT.

Results: Peak ankle dorsiflexion, ΔHHb, and ΔSmO decreased significantly after transplantation as compared to measurements taken before transplantation (p < 0.01). The change in peak ankle dorsiflexion from before to after HSCT was not significantly correlated with total steroid dose. However, ΔHHb and ΔSmO from before to after HSCT were significantly correlated with total steroid dose (p < 0.01).

Conclusion: This study showed that higher corticosteroid doses are associated with diminished skeletal muscle O consumption and skeletal muscle O demand relative to supply. Therefore, rehabilitation staff, nurses, and physicians should take note of these findings in patients undergoing HSCT. Moreover, physiotherapists should be carefully measuring muscle oxidative metabolism on skeletal muscle when planning physical exercise in such patients.
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http://dx.doi.org/10.1007/978-3-030-48238-1_14DOI Listing
May 2021

Prognostic factors in salvage transplantation for graft failure following allogeneic hematopoietic stem cell transplantation.

Bone Marrow Transplant 2021 Apr 29. Epub 2021 Apr 29.

Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan.

Although graft failure (GF) is a fatal complication after allogeneic stem cell transplantation (SCT), no mortality risk assessments after salvage SCT have been reported. We developed a comprehensive prognostic scoring system consisting of patient and comorbidity factors with 470 patients as a training cohort out of 940; these patients underwent salvage SCT for GF. The multivariate analysis demonstrated that older age, poorer performance status, a continuation of antimicrobial treatment, and severe organ dysfunction were independently associated with worse overall survival (OS) and non-relapse mortality (NRM). Based on each factor's hazard ratio, weighted scores of 1-3 were assigned to these factors. Using the summed scores (0-8), a prognostic scoring system successfully stratified outcomes after salvage SCT in the cohort. For patients in the low (0-2, n = 122), intermediate (3-4, n = 209), and high score (5-8, n = 110) groups, the 1-year OS was 62.8%, 40.8%, and 14.2%, respectively (P < 0.001), whereas the 1-year NRM was 24.1%, 43.9%, and 72.7%, respectively (P < 0.001). The prognostic value of the scoring system was confirmed in the validation cohort (n = 470). Our scoring system is useful for predicting survival after salvage SCT.
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http://dx.doi.org/10.1038/s41409-021-01310-0DOI Listing
April 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.
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http://dx.doi.org/10.1038/s41409-021-01291-0DOI Listing
April 2021

Single Cord Blood Transplantation Versus Unmanipulated Haploidentical Transplantation for Adults with Acute Myeloid Leukemia in Complete Remission.

Transplant Cell Ther 2021 04 28;27(4):334.e1-334.e11. Epub 2021 Jan 28.

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

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative post-remission therapy for adult patients with acute myeloid leukemia (AML) in complete remission (CR). The availability of alternative human leukocyte antigen (HLA)-mismatched donors, such as cord blood and haploidentical related donors, could allow patients to receive allogeneic HCT who are without an HLA-matched sibling or unrelated donor. The use of these alternative donors is preferable for patients with advanced disease due to the rapid availability. However, comparative data for cord blood transplantation (CBT) and haploidentical related donor transplantation (haplo-HCT) are limited for adult patients with AML in CR. We sought to compare overall survival (OS); leukemia-free survival (LFS); graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS); and chronic GVHD-free, relapse-free survival (CRFS) between single-unit CBT (SCBT) and haplo-HCT recipients for adult patients with intermediate- or poor-risk AML in CR. We retrospectively analyzed and compared the results of allogeneic hematopoietic cell transplantation in 1313 adult patients with intermediate- or poor-risk AML in CR who received either SCBT (n = 1102) or unmanipulated haplo-HCT (n = 211) between 2007 and 2018 in Japan. Among the whole cohort, the cumulative incidences of neutrophil and platelet recovery were significantly lower in SCBT recipients compared with those in haplo-HCT recipients (P < .001 for neutrophil, P < .001 for platelet). SCBT was significantly associated with a higher incidence of grade II to IV acute GVHD and lower incidence of extensive chronic GVHD compared to haplo-HCT (P = .013 for grades II to IV acute GVHD; P = .006 for extensive chronic GVHD). Haplo-HCT recipients developed a higher incidence of cytomegalovirus (CMV) antigenemia compared to SCBT recipients (P = .004). In the multivariate analysis, there were no significant differences for grades III or IV acute GVHD (hazard ratio [HR], 1.17; 95% confidence interval [CI], .88 to 1.57; P = .26), relapse incidence (HR, 1.09; 95% CI, .76 to 1.58; P = .61), non-relapse mortality (HR, .83; 95% CI, .58 to 1.18; P = .32), OS (HR, .92; 95% CI, .70 to 1.20; P = .56), LFS (HR, .94; 95% CI, .73 to 1.21; P = .67), GRFS (HR, 1.12; 95% CI, .90 to 1.40; P = .27), or CRFS (HR, 1.15; 95% CI, .92 to 1.44; P = .19) between the two donor types. In the propensity score matching analysis, which identified 180 patients in each cohort, there were no significant differences in transplant outcomes between the two donor types, except for delayed neutrophil (P < .001) and platelet recovery (P < .001) and a higher incidence of grades II to IV acute GVHD (P = .052) in SCBT. SCBT and unmanipulated haplo-HCT had similar survival outcomes for adult patients with AML in CR despite the lower hematopoietic recovery and higher grade II to IV acute GVHD in SCBT recipients and the higher CMV antigenemia in haplo-HCT recipients.
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http://dx.doi.org/10.1016/j.jtct.2021.01.023DOI Listing
April 2021

Muscle oxygen extraction and lung function are related to exercise tolerance after allogeneic hematopoietic stem cell transplantation.

Support Care Cancer 2021 Mar 30. Epub 2021 Mar 30.

Department of Rehabilitation Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

Purpose: This study aimed to investigate the relationship between exercise intolerance, muscle oxidative metabolism, and cardiopulmonary function following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a sterile isolation room setting.

Methods: This was a prospective observational cohort study conducted in a single center. Fourteen patients with hematopoietic malignancies who had undergone allo-HSCT were included in this study from June 2015 to April 2020. Patients received donor HSCT after high dose-chemotherapy and total-body irradiation. Physical activity was limited during treatments. Outcome measures included body anthropometric measurements, exercise tolerance tests using the ramp protocol, pulmonary function tests, and near-infrared spectroscopy (NIRS) measurements. Data of pre- and posttransplant measurements were compared using the paired t test or nonparametric Wilcoxon U test. Associations were assessed using the Pearson or nonparametric Spearman correlations.

Results: NIRS showed reduced muscle consumption and extraction of oxygen in the posttransplant period compared to the pretransplant period (ΔStO pre: -18.6% vs. post: -13.0%, P = 0.04; ΔHHb pre: 4.21μmol/l vs. post: 3.31μmol/l: P = 0.048). Exercise tolerance had reduced following allo-HSCT (Peak workload pre: 70.3 W vs. post: 58.0 W: P = 0.014). Furthermore, exercise intolerance was associated with pulmonary function, muscle oxygen consumption, and muscle oxygen extraction (all P <0.05).

Conclusion: This analysis revealed that exercise intolerance following allo-HSCT was associated with pulmonary dysfunction and muscle oxidative dysfunction. These findings could help identify the physical function associated with impaired tissue oxygen transport leading to exercise intolerance following allo-HSCT.
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http://dx.doi.org/10.1007/s00520-021-06178-wDOI Listing
March 2021

A multicenter phase II study of intrabone single-unit cord blood transplantation without antithymocyte globulin.

Ann Hematol 2021 Mar 11;100(3):743-752. Epub 2021 Jan 11.

Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.

To overcome the delayed or failed engraftment after unrelated cord blood transplantation (CBT), we conducted a multicenter phase II study of intrabone single-unit CBT without antithymocyte globulin (ATG) for adult patients with hematological malignancies (UMIN-CTR, UMIN000020997). Sixty-four patients received an intrabone injection of unwashed (n = 61) or washed (n = 3) cord blood after local anesthesia. All injection-related adverse events were mild and resolved spontaneously. Sixty-two patients were evaluable for the efficacy of intrabone CBT of serological HLA-A, -B, and -DR ≥ 4/6 matched cord blood with a median number of 2.57 × 10/kg cryopreserved total nucleated cells. The probability of survival with neutrophil engraftment on day 28 was 77.4% (95% confidence interval, 67.0-85.8%), which exceeded the threshold value. The cumulative incidences of neutrophils ≥ 0.5 × 10/L on day 60 was 80.6% (68.2-88.6%), with a median time to recovery of 21 days after transplantation. The cumulative incidences of platelets ≥ 20 × 10/L and platelets ≥ 50 × 10/L on day 100 were 75.8% (62.6-84.9%) and 72.6% (59.4-82.1%), respectively, with median time to platelets ≥ 20 × 10/L and platelets ≥ 50 × 10/L of 38 and 45 days after transplantation, respectively. The cumulative incidences of grade II-IV and III-IV acute graft-versus-host disease were 29.0% and 6.5%, respectively. All responded to steroid therapy, and secondary treatments were not required. The present study suggests the efficacy of intrabone single-unit CBT without ATG in terms of early engraftment and controllable acute graft-versus-host disease.
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http://dx.doi.org/10.1007/s00277-020-04365-zDOI Listing
March 2021

The ADVIA2120i parameter Revised %MICRO is a surrogate marker of schistocyte formation after hematopoietic stem cell transplantation.

J Med Invest 2020 ;67(3.4):250-254

Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

Objectives : Hematopoietic stem cell transplantation (HSCT)-associated thrombotic microangiopathy (TA-TMA) is an important early post-treatment condition. This study evaluated the Revised %MICRO, a parameter obtained from the ADVIA 2120i automated blood cell counter, as a surrogate marker of the schistocyte ratio. We hypothesized that individual differences between the %MICRO value and schistocyte ratio would remain constant. Design and Methods: EDTA-2K-treated peripheral blood samples were collected from 19 patients who underwent allogeneic HSCT from April 2014 to September 2018. First, the baseline difference, X, was calculated using a sample from the first day after HSCT as X = %MICRO (first day) - schistocyte ratio (first day). Next, the Revised %MICRO for each subsequent day was calculated as Revised %MICRO = %MICRO - X. We evaluated correlations of the schistocyte ratio with the calculated %MICRO and Revised %MICRO and the RBC fragment, RBC distribution width, %MICRO and Revised %MICRO data obtained from the ADVIA 2120i. Results : The mean schistocyte percentage and Revised %MICRO were both 0.4% ± 0.6. RBC fragments correlated weakly with the %MICRO and schistocyte ratio, respectively (r = 0.162 and r = 0.771, respectively), whereas the Revised %MICRO correlated strongly with the schistocyte ratio (r = 0.893). Conclusion : The Revised %MICRO appears to be a good surrogate of the schistocyte ratio in a clinical setting. J. Med. Invest. 67 : 250-254, August, 2020.
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http://dx.doi.org/10.2152/jmi.67.250DOI Listing
January 2020

Decrease in voriconazole concentration-to-dose ratio after letermovir initiation: a retrospective, observational study.

Bone Marrow Transplant 2021 04 25;56(4):949-951. Epub 2020 Oct 25.

Department of Pharmacy, Hyogo College of Medicine College Hospital, Hyogo, 663-8501, Japan.

Letermovir is used to prevent cytomegalovirus infection in hematopoietic stem cell transplantation (HSCT) recipients. Although this agent decreases voriconazole exposure in healthy individuals, the effect of coadministration of letermovir and voriconazole in HSCT recipients is unknown. This retrospective, observational, single-center study was conducted between January 2016 and July 2019 to examine the voriconazole concentration-to-dose ratio over three periods: (A) (days -7 to -1 [day 0: day of HCST]), (B) (days 4-10), and (C) (days 11-17). Forty-two HSCT recipients administered voriconazole were divided into the following two groups based on letermovir coadministration: letermovir (n = 15) and control (n = 27). The percent change (-33.2%, p < 0.05) in the voriconazole concentration-to-dose ratio from periods A to C in the letermovir group was significantly lower than that in the control group. Therefore, frequent therapeutic drug monitoring of voriconazole concentrations and subsequent dose adjustments should be performed regularly in HSCT recipients.
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http://dx.doi.org/10.1038/s41409-020-01093-wDOI Listing
April 2021

Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with paroxysmal nocturnal hemoglobinuria.

Int J Hematol 2021 Jan 5;113(1):122-127. Epub 2020 Sep 5.

Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

The safety and efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) remain unclear. Therefore, we retrospectively analyzed the outcomes of 42 adult patients with PNH who underwent allogeneic HSCT using the registry database of the Japan Society for Hematopoietic Cell Transplantation. The median patient age was 32.5 years. The number of packed red cell (PRC) transfusions was < 20 times in 19 patients and ≥ 20 times in 16; 7 patients had missing data. Stem cell sources were bone marrow (N = 15) or peripheral blood (N = 13) from a related donor or bone marrow (N = 11) and cord blood (N = 3) from an unrelated donor. The cumulative incidence of neutrophil engraftment at day 40 was 81%. Six patients died before engraftment, and the 6-year overall survival (OS) was 74%. The OS of patients with < 20 pretransplant PRC transfusions was significantly higher than that of patients with ≥ 20 pretransplant PRC transfusions (95% vs. 63%; P < 0.05). Moreover, the OS of patients aged < 30 years was significantly higher than that of patients aged ≥ 30 years (90% vs. 59%; P < 0.05). Allogeneic HSCT for PNH could provide favorable survival; however, pretransplant transfusion burden and patient age should be considered when deciding the timing of allogeneic HSCT.
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http://dx.doi.org/10.1007/s12185-020-02982-yDOI Listing
January 2021

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

Toxoplasmic Encephalitis Followed by Primary EBV-Associated Post-Transplant Lymphoproliferative Disorder of the Central Nervous System in a Patient Undergoing Allogeneic Hematopoietic Stem Cell Transplant: A Case Report.

Transplant Proc 2020 Nov 29;52(9):2858-2860. Epub 2020 Aug 29.

Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.

Toxoplasmic encephalitis (TE) and post-transplant lymphoproliferative disorder of the central nervous system (CNS-PTLD) are major complications after allogeneic hematopoietic stem cell transplant (allo-SCT); both are fatal without timely diagnosis and disease-specific treatment. Differential diagnosis of TE and CNS-PTLD can be challenging because brain biopsy, a gold standard for diagnosis, is sometimes not possible, owing to poor patient condition after allo-SCT. Here, we describe a case of isolated CNS-PTLD arising during the therapeutic course of TE. A 51-year-old man was admitted with mental abnormalities and fever on Day 106 after allo-SCT to treat myelodysplastic syndrome. Magnetic resonance imaging (MRI) revealed multiple nodular and ring-enhanced lesions in the brain, and the result of polymerase chain reaction (PCR) for Toxoplasma gondii in cerebrospinal fluid was positive; therefore, he was diagnosed with TE. Anti-Toxoplasma therapy led to clinical improvement, and the result of subsequent PCR was negative. However, he developed left-sided hemiplegia on Day 306. Head MRI revealed a new lesion and a growing lesion, presenting as ring-enhanced nodules. Brain biopsy was performed, and a pathologic diagnosis of Epstein-Barr virus-associated CNS-PTLD was made. There was no evidence of TE. He was treated successfully by reducing immunosuppressants, followed by rituximab administration and a donor lymphocyte infusion, resulting in complete remission. While T.gondii-specific PCR has great value for diagnosis of TE, CNS-PTLD can be diagnosed only by brain biopsy; hence, brain biopsy may be warranted in cases of suspected PTLD.
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http://dx.doi.org/10.1016/j.transproceed.2020.08.002DOI Listing
November 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.
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http://dx.doi.org/10.1038/s41409-020-01011-0DOI Listing
January 2021

Allogeneic hematopoietic stem cell transplantation from a 2-HLA-haplotype-mismatched family donor for posttransplant relapse: a prospective phase I/II study.

Bone Marrow Transplant 2021 01 20;56(1):70-83. Epub 2020 Jun 20.

Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

HLA haploidentical hematopoietic stem cell transplantation (HSCT), i.e., HSCT from a 1-HLA-haplotype-mismatched family donor, has been successfully performed even as a second transplantation for posttransplant relapse. Is the haploidentical the limit of HLA mismatches in HSCT? In order to explore the possibility of HLA-mismatched HSCT from family donors beyond haploidentical relatives, we conducted a prospective phase I/II study of 2-HLA-haplotype-mismatched HSCT (2-haplo-mismatch HSCT). We enrolled 30 patients with posttransplant relapse (acute myeloid leukemia: 18, acute lymphoblastic leukemia: 11, non-Hodgkin lymphoma: 1). 2-haplo-mismatch HSCT was performed as the second to sixth transplantations. The donors were siblings (n = 12), cousins (n = 16), and second cousins (n = 2). The conditioning regimen consisted of fludarabine, cytarabine, melphalan, low-dose anti-thymocyte globulin, and 3 Gy of total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, methylprednisolone, and mycophenolate mofetil. All patients achieved neutrophil engraftment, except for a case of early death. The cumulative incidences of grades II-IV and III-IV acute GVHD were 36.7% and 16.7%, respectively. The overall survival at 1 year, relapse, and non-relapse mortality rates was 30.1%, 38.9%, and 44.3%, respectively. Considering the poor prognosis of posttransplant relapse, 2-haplo-mismatch HSCT can be an alternative option in a second or third transplantation.
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http://dx.doi.org/10.1038/s41409-020-0980-8DOI Listing
January 2021

Effects of antifungal stewardship using therapeutic drug monitoring in voriconazole therapy on the prevention and control of hepatotoxicity and visual symptoms: A multicentre study conducted in Japan.

Mycoses 2020 Aug 25;63(8):779-786. Epub 2020 Jun 25.

Department of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan.

Background: Hepatotoxicity and visual symptoms are common adverse effects (AEs) of voriconazole therapy.

Objective: To retrospectively evaluate the effects of treatment modification based on therapeutic drug monitoring on AEs in patients undergoing voriconazole therapy.

Methods: The target voriconazole trough concentration (C ) was 1-5 µg/mL. Receiver operating characteristic curves were used to determine C cut-offs for AEs.

Results: A total of 401 patients were included. Among 108 patients with high initial C , voriconazole was discontinued in 32 and the dose was reduced in 71. Among 44 patients with low initial C , voriconazole was discontinued in 4 and the dose was increased in 19. Hepatotoxicity occurred in 6.0% of patients, after a median of 10 days. Visual symptoms were evident in 9.5% of patients after a median of 4 days. Initial C was significantly associated with visual symptoms but not hepatotoxicity, which suggested the effect of treatment modification on hepatotoxicity. However, both hepatotoxicity and visual symptoms were significantly correlated with C at the onset of AEs, and the C cut-offs were 3.5 μg/mL for hepatotoxicity and 4.2 μg/mL for visual symptoms. Voriconazole was discontinued after the occurrence of AEs in 62.5% of patients with hepatotoxicity but only 26.3% of patients with visual symptoms. With dose adjustment, treatment was completed in 8/9 patients with hepatotoxicity and 27/28 patients with visual symptoms.

Conclusions: A significant preventive effect was demonstrated on hepatotoxicity, but not on visual symptoms because of earlier occurrence. With treatment modification after the occurrence of AEs, most patients completed therapy.
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http://dx.doi.org/10.1111/myc.13129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496238PMC
August 2020

Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia conducted in Japan during the past quarter century.

Ann Hematol 2020 Jun 4;99(6):1351-1360. Epub 2020 May 4.

The Jikei University School of Medicine, Tokyo, Japan.

Acute myeloid leukemia (AML) represents the most common indication for allogeneic hematopoietic cell transplantation (HCT). This study aimed to address the implementation status of allogeneic HCT for adults with AML in Japan and to provide a comprehensive overview of post-transplant outcomes. For this purpose, we analyzed data of 15,186 patients undergoing allogeneic HCT between 1992 and 2016 who were consecutively reported to the Japanese nationwide transplantation registry. The constant increase in the annual number of transplantations was clearly attributable to the growth of unrelated transplantation, and umbilical cord blood transplantation currently accounts for one-third of all allogeneic HCTs. The proportion of older patients has increased steadily since 2000, approximately, in parallel with the introduction of reduced-intensity conditioning. The probability of overall survival (OS) was estimated at 41% (95% confidence interval (CI), 40-42%) for the entire cohort, 56% (95% CI, 55-57%) for patients transplanted in complete remission (CR), and 22% (95% CI, 21-23%) for those transplanted in non-CR. Multivariate analysis identified age, sex, performance status, disease status, cytogenetic risk, donor type, graft source, sex mismatch between the donor and the recipient, and year of transplantation as factors significantly associated with OS. These findings represent the real-world data in Japan, showing the changes in transplantation practice and a detailed estimation of post-transplant outcomes.
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http://dx.doi.org/10.1007/s00277-020-04051-0DOI Listing
June 2020

Tacrolimus Concentration after Letermovir Initiation in Hematopoietic Stem Cell Transplantation Recipients Receiving Voriconazole: A Retrospective, Observational Study.

Int J Med Sci 2020 15;17(7):859-864. Epub 2020 Mar 15.

Department of Pharmacy, Hyogo College of Medicine College Hospital, Nishinomiya, Hyogo 663-8501, Japan.

Letermovir (LMV) is a new antiviral drug used to prevent cytomegalovirus infection in hematopoietic stem cell transplantation (HSCT) recipients. It has been reported to increase tacrolimus (TAC) exposure and decrease voriconazole (VRCZ) exposure in healthy participants. However, VRCZ inhibits the metabolism of TAC. Thus, the effects of LMV on TAC exposure in patients receiving VRCZ are unknown. This retrospective, observational, single-center study was conducted between May 2018 and April 2019. The TAC concentration/dose (C/D) ratio, VRCZ concentration, and VRCZ C/D ratio for 7 days before and for the first and second 7-day periods after the initiation of LMV administration were evaluated. Fourteen HSCT recipients receiving VRCZ were enrolled. There was no significant difference in the TAC C/D ratio for 7 days before and for the first and second 7-day periods after initiating LMV administration (median: 866 [IQR: 653-953], 842 [IQR: 636-1031], and 906 [IQR: 824-1210] [ng/mL]/[mg/kg], respectively). In contrast, the VRCZ C/D ratio and concentration for the first and second 7-day periods after LMV initiation were significantly lower than those before initiating LMV administration (mean 1.11 ± 0.07, 0.12 ± 0.08, and 0.22 ± 0.12 [μg/mL]/[mg/kg] and 0.7 ± 0.5, 0.8 ± 0.5, and 1.3 ± 0.7 μg/mL, respectively; n = 12). This can be explained by the increase in TAC concentration caused by CYP3A4 inhibition due to LMV and by the decrease in TAC concentration ascribed to the decrease in VRCZ concentration by CYP2C19 induction due to LMV. These results suggest that it is unnecessary to adjust the dose of TAC based on LMV initiation; however, it is necessary to adjust the dose of TAC based on conventional TAC concentration measurements.
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http://dx.doi.org/10.7150/ijms.42011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163365PMC
February 2021

Heterogeneous impact of cytomegalovirus reactivation on nonrelapse mortality in hematopoietic stem cell transplantation.

Blood Adv 2020 03;4(6):1051-1061

Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.

Cytomegalovirus (CMV) infection is a major complication in allogeneic stem cell transplantation. The utility of CMV prophylaxis with letermovir has been reported; however, the specific applications remain unclear. In this study, we retrospectively analyzed large-scale registry data (N = 10 480) to clarify the risk factors for nonrelapse mortality (NRM) in connection with CMV reactivation. First, we identified risk factors for CMV reactivation using multivariate analysis and developed a scoring model. Although the model effectively stratified reactivation risk into 3 groups (43.7% vs 60.9% vs 71.5%; P < .001), the 3-year NRM was significantly higher in patients with CMV reactivation, even in the low (20.9% vs 13.0%, P < .001), intermediate (21.4% vs 15.6%; P < .001), and high (29.3% vs 18.0%; P < .001) reactivation risk groups. Next, survival analysis considering competing risks, time-dependent covariates, and interaction terms for exploring the heterogeneous impact of CMV reactivation on NRM in the training cohort revealed that chronic myeloid leukemia (CML) (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.05-2.96; P = .033), good performance status (PS) (HR, 1.42; 95% CI, 1.04-1.94; P = .028), HLA-matched donor (HR, 1.34; 95% CI, 1.06-1.70; P = .013), and standard-risk disease (HR, 1.28; 95% CI, 1.04-1.58; P = .022) were associated with increased NRM. In the test cohort, CMV reactivation was significantly associated with increased 3-year NRM among patients with 2 to 4 factors (22.1% vs 13.1%; P < .001) but was comparable among patients with 0 or 1 factor (23.2% vs 20.4%; P = .62). We propose that CMV prophylaxis should be determined based on reactivation risk, as well as these other factors.
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http://dx.doi.org/10.1182/bloodadvances.2019000814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094017PMC
March 2020

Echinocandins versus non-echinocandins for empirical antifungal therapy in patients with hematological disease with febrile neutropenia: A systematic review and meta-analysis.

J Infect Chemother 2020 Jun 11;26(6):596-603. Epub 2020 Mar 11.

Committee of Clinical Practice Guidelines for the Diagnosis and Management of Invasive Candidiasis 2020 by the Japanese Society for Medical Mycology, Japan; Emergency Department, University of Occupational and Environmental Health, Fukuoka, Japan.

Empirical antifungal therapy is recommended in high-risk patients who have persistent febrile neutropenia (FN) despite broad-spectrum antibiotic therapy. Based on high-quality evidence, most guidelines recommend caspofungin. The aim of this study was to clarify whether echinocandins, including micafungin, are associated with improved clinical outcomes in patients with persistent FN. We conducted a meta-analysis of randomized controlled trials (RCTs) of empirical therapy with echinocandins and non-echinocandins for FN in patients with hematological disease. The primary outcome was all-cause mortality within 7 days after completion of therapy. Secondary outcomes included treatment success, and discontinuation of therapy because of adverse events. For subgroup analysis, we compared RCTs of echinocandins with liposomal amphotericin B. Six RCTs (four that evaluated caspofungin and two that evaluated micafungin) were included in the meta-analysis. Mortality and adverse events in echinocandin-treated patients were significantly lower than in those treated with non-echinocandins [risk ratio (RR) 0.70, 95% confidence interval (CI) 0.49-0.99; RR 0.48, 95% CI 0.33-0.71, respectively]. There was no significant difference in treatment success (RR 1.09, 95% CI 0.87-1.36). Mortality and adverse events in echinocandin-treated patients were significantly lower than in those treated with liposomal amphotericin B (RR 0.68, 95% CI 0.46-0.99; RR 0.53, 95% CI 0.37-0.74, respectively). In conclusion, patients with persistent FN treated with echinocandins had decreased risk of death and adverse events. Both caspofungin and micafungin may be recommended as first-line empirical antifungal therapy in these patients. However, the small number of enrolled patients and the lack of RCTs involving pediatric patients should be considered when using micafungin.
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http://dx.doi.org/10.1016/j.jiac.2020.01.015DOI Listing
June 2020

Comparison of the outcomes after haploidentical and cord blood salvage transplantations for graft failure following allogeneic hematopoietic stem cell transplantation.

Bone Marrow Transplant 2020 09 12;55(9):1784-1795. Epub 2020 Feb 12.

Department of Hematology, Oita University Hospital, Yufu, Japan.

Graft failure (GF) is a life-threatening complication after allogeneic stem cell transplantation (SCT). Although salvage SCTs can be performed with haploidentical donor (HID) or cord blood (CB), no study has compared the performances of these two sources. Using nationwide registration data, we compared the transplant outcomes of patients who developed GF and underwent salvage transplantation from HID (n = 129) and CB (n = 570) from 2007 to 2016. The HID group demonstrated better neutrophil recovery (79.7 vs. 52.5% at 30 days, P < 0.001). With a median follow-up of 3 years, both groups demonstrated similar overall survival (OS) and nonrelapse mortality (NRM; 1-year OS, 33.1 vs. 34.6% and 1-year NRM, 45.1 vs. 49.8% for the HID and CB groups). After adjustments for other covariates, OS did not differ in both groups. However, HID was associated with a lower NRM (hazard ratio, 0.71; P = 0.038) than CB. The incidence of acute graft-versus-host disease (GVHD)-related deaths was significantly higher in the HID group, although infection-related deaths were observed more frequently in the CB group. HID may be a promising salvage SCT option after GF due to its faster engraftment and low NRM.
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http://dx.doi.org/10.1038/s41409-020-0821-9DOI Listing
September 2020

Allogeneic hematopoietic stem cell transplantation for adult patients with B-cell acute lymphoblastic leukemia harboring t(1;19)(q23;p13.3); comparison with normal karyotype.

Bone Marrow Transplant 2020 07 10;55(7):1337-1346. Epub 2020 Feb 10.

Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.

There are few reports on allogeneic hematopoietic stem cell transplantation (allo-HSCT) for adult B-cell acute lymphoblastic leukemia (B-ALL) harboring t(1;19)(q23;p13.3). We used nationwide registry data of Japan for 2003-2016 to evaluate transplant outcomes and clarified prognostic factors among adult allo-HSCT recipients with B-ALL harboring t(1;19)(q23;p13.3) (n = 125). Compared with cytogenetically normal (CN) B-ALL patients (n = 1057), their 3-year overall survival (OS) rates were comparable (55.4% for t(1;19) and 54.4% for CN; P = 0.76). Considering only patients in first complete hematological remission (CR1), the 3-year OS rates remained comparable (70.5% for t(1;19) and 67.8% for CN; P = 0.86). For t(1;19) patients in CR1, minimal residual disease (MRD) at transplantation was associated with relatively worse outcomes. The 3-year OS rates were 43.6% for patients with MRD and 77.4% for those without it (P = 0.016). The 3-year relapse rates were 54.5% for patients with MRD and 12.8% for those without it (P < 0.001). Multivariate analyses revealed that MRD at transplantation was a significant risk factor for OS and relapse. In the high-intensity chemotherapy era, t(1;19)(q23;p13.3) did not have a poorer posttransplant prognosis than the normal karyotype. However, even for patients in CR1, MRD at transplantation was associated with comparatively worse OS and higher relapse rates.
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http://dx.doi.org/10.1038/s41409-020-0816-6DOI Listing
July 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.
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http://dx.doi.org/10.1002/hon.2714DOI Listing
April 2020

Relationship Between Exercise Capacity and Muscle OHb Saturation in Patients Before Hematopoietic Stem-Cell Transplantation.

Adv Exp Med Biol 2020 ;1232:215-221

Department of Physical Medicine and Rehabilitation, Hyogo College of Medicine, Nishinomiya, Japan.

Patients with hematological malignancy might already have decreased muscle oxygen saturation at rest and exercise capacity before undergoing hematopoietic stem cell transplantation (HSCT). However, to date, no studies have investigated the relationship between exercise capacity and muscle oxygen saturation at rest in these patients. Therefore, purpose of this study was to investigate the relationship between exercise capacity and muscle oxygen-hemoglobin (O2Hb) saturation (SmO2) at rest and patients' hemoglobin level before undergoing HSCT.

Methods: This study included 60 men with hematologic disease who underwent allo-HSCT. Patients performed a 6-minute walk test (6MWT) to determine exercise capacity, and muscle O2Hb saturation at rest was evaluatabed using near-infrared spectroscopy (BOM-L1TRW, Omegawave Inc., Japan); hemoglobin levels in hematological malignancy patients before undergoing HSCT were also evaluated.

Results: There was a significant correlation between the 6MWT and muscle O2Hb saturation at rest in hematological malignancy patients (p < 0.05). Additionally, the 6MWT was significantly correlated to the hemoglobin level (p < 0.05). Furthermore, muscle O2Hb saturation at rest was significantly related to hemoglobin level (p < 0.05).

Conclusion: In patients with hematological malignancy, a relationship exists between exercise capacity, muscle O2Hb saturation, and hemoglobin level before they undergo HSCT. Therefore, rehabilitation staff, nurses, and physicians should recognize these relationships in patients who undergo allo-HSCT. Moreover, physiotherapists may need to promote muscle oxidative metabolism through exercise to increase exercise capacity in these patients.
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http://dx.doi.org/10.1007/978-3-030-34461-0_27DOI Listing
January 2020

Relationship Between Muscle Oxygen Saturation and Exercise Load in Patients with Malignant Hematopoietic Disease.

Adv Exp Med Biol 2020 ;1232:201-207

Department of Rehabilitation Medicine, Hyogo College of Medicine, Nishinomiya, Japan.

Our previous research confirmed that patients with malignant hematopoietic disease already had a low hemoglobin level before allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no study has determined whether a correlation exists between exercise load, hemoglobin level, and muscle oxygen saturation (SmO), during exercise. Therefore, the purpose of this study was to investigate whether near-infrared spectroscopy (NIRS)-derived SmO is associated with exercise load, as determined by a dynamometer, before allo-HSCT. This study included 19 male patients who received allo-HSCT in Hyogo College of Medicine Hospital (Japan) between November 2009 and October 2012. Patients performed isometric repeated dorsiflexion at 50% maximum voluntary contraction for 180 s to determine exercise load, and SmO was evaluated during exercise at the same time using NIRS (BOM-L1TRW, Omega Wave, Inc., Japan). The hemoglobin level was also evaluated before allo-HSCT. Patients with hematopoietic disease before allo-HSCT already had a low hemoglobin level. There was a significant correlation between exercise load and ∆SmO; however, the hemoglobin level was not correlated with exercise load. In these patients, exercise load might be affected by muscle oxygen consumption rather than by the hemoglobin level. This finding shows that NIRS can used to assess fatigue in patients with malignant hematopoietic disease.
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http://dx.doi.org/10.1007/978-3-030-34461-0_25DOI Listing
January 2020
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