Publications by authors named "Yozo Nakazawa"

174 Publications

A lymphodepleted non-human primate model for the assessment of acute on-target and off-tumor toxicity of human chimeric antigen receptor-T cells.

Clin Transl Immunology 2021 3;10(6):e1291. Epub 2021 Jun 3.

Center for Advanced Research of Gene and Cell Therapy in Shinshu University (CARS) Shinshu University School of Medicine Matsumoto Japan.

Objectives: Chimeric antigen receptor (CAR)-T cell therapy possesses the potential to cause unexpected on-target toxicities that may be life-threatening. Non-human primates (NHPs) share considerable structural homology and expression profiles of most proteins with humans and are therefore utilised as an animal model for non-clinical safety studies. We have developed a lymphodepleted NHP model by conditioning the animals with immunosuppressive chemotherapy designed to simulate clinical practice conditions, to induce transient mixed chimerism before the administration of human CAR-T cells redirected to target Ephrin type-B receptor 4 (EPHB4-CAR-T cells) to evaluate the toxicity of these cells.

Methods: We administered 60 mg m day of fludarabine for 4 days and 30 mg kg day of cyclophosphamide for 2 days intravenously to cynomolgus macaques for lymphodepletion; then, 3.3 × 10 kg of non-transduced or EPHB4-CAR-T cells was infused into the macaques, respectively. All macaques were closely monitored and evaluated for potential toxicity for 7 days.

Results: Lymphodepletion was successfully achieved on day -1 before T-cell infusion and persisted over 7 days without severe organ toxicities. A single administration of human EPHB4-CAR-T cells did not induce overt organ toxicities, although EPHB4-CAR-T cells were activated  as evidenced by the elevation in copy numbers of the CAR transgene 24 h after infusion.

Conclusion: Although this NHP model is limited for the full evaluation of toxicity of human CAR-T cells and the conditioning protocol should be further optimised, this lymphodepleted NHP model could be used to assess acute on-target/off-tumor toxicities of CAR-T cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cti2.1291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175993PMC
June 2021

Impact of acute kidney injury on overall survival in children and young adults undergoing allogeneic hematopoietic stem cell transplantation.

Pediatr Blood Cancer 2021 Jun 4:e29167. Epub 2021 Jun 4.

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.

Background: Acute kidney injury (AKI) is a complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Increasing severity of AKI is associated with an increased risk of death. However, the impact of AKI in patients with malignant versus nonmalignant disease has not been reported. We investigated the incidence of AKI within the first 100 days after allo-HSCT and the impact of AKI on both 3-year overall survival (OS) and cumulative incidence of death after allo-HSCT in all patients and in patients with/without malignant primary diseases.

Methods: We performed a retrospective analysis of 107 consecutive pediatric and young adult patients who received their first allo-HSCT. AKI was classified into three grades according to the Acute Kidney Injury Network classification system.

Results: The cumulative incidences of AKI stages 1-3, 2-3, and 3, at day 100 after allo-HSCT were 34.6% (95% confidence interval [CI], 25.7%-43.6%), 17.8% (95% CI, 11.2%-25.6%), and 3.7% (95% CI, 1.2%-8.6%), respectively. OS was reduced for patients with AKI compared with patients without AKI (60.4% vs. 79.6%, p = .038). The cumulative incidence of death in the AKI group with nonmalignant disease was significantly higher than that in the no-AKI group (44.4% vs. 0%, p = .003).

Conclusion: AKI after allo-HSCT was not only a frequent event but also related to reduced OS. We recommend that all patients receiving allo-HSCT, especially patients with nonmalignant diseases, be closely monitored for AKI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.29167DOI Listing
June 2021

Mutated GM-CSF-based CAR-T cells targeting CD116/CD131 complexes exhibit enhanced anti-tumor effects against acute myeloid leukaemia.

Clin Transl Immunology 2021 6;10(5):e1282. Epub 2021 May 6.

Department of Pediatrics Shinshu University School of Medicine Matsumoto Japan.

Objectives: As the prognosis of relapsed/refractory (R/R) acute myeloid leukaemia (AML) remains poor, novel treatment strategies are urgently needed. Clinical trials have shown that chimeric antigen receptor (CAR)-T cells for AML are more challenging than those targeting CD19 in B-cell malignancies. We recently developed -modified ligand-based CAR-T cells that target CD116/CD131 complexes, also known as the GM-CSF receptor (GMR), for the treatment of juvenile myelomonocytic leukaemia. This study therefore aimed to develop a novel therapeutic method for R/R AML using GMR CAR-T cells.

Methods: To further improve the efficacy of the original GMR CAR-T cells, we have developed novel GMR CAR vectors incorporating a mutated GM-CSF for the antigen-binding domain and G4S spacer. All GMR CAR-T cells were generated using a -based gene transfer system. The anti-tumor effect of GMR CAR-T cells was tested in mouse AML xenograft models.

Results: Nearly 80% of the AML cells predominant in myelomonocytic leukaemia were found to express CD116. GMR CAR-T cells exhibited potent cytotoxic activities against CD116 AML cells . Furthermore, GMR CAR-T cells incorporating a G4S spacer significantly improved long-term and anti-tumor effects. By employing a mutated GM-CSF at residue 21 (E21K), the anti-tumor effects of GMR CAR-T cells were also improved especially in long-term settings. Although GMR CAR-T cells exerted cytotoxic effects on normal monocytes, their lethality on normal neutrophils, T cells, B cells and NK cells was minimal.

Conclusions: GMR CAR-T cell therapy represents a promising strategy for CD116 R/R AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cti2.1282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102137PMC
May 2021

Multi-institutional survey of thymic carcinoma patients in Hokushin region.

J Cancer Res Clin Oncol 2021 May 8. Epub 2021 May 8.

Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.

Background: Thymic carcinoma is a rare neoplasm, and its prognosis is very poor. The purpose of this study was to validate the clinical and epidemiological factors, diagnosis and initial treatment of thymic carcinoma among all patients diagnosed in the registered hospital group.

Methods: We surveyed retrospective data from 152,921 cancer patients in 22 principal hospitals.

Results: A total of 88 thymic carcinoma cases were newly diagnosed. These patients were 50 men and 38 women, with a median age of 66 years old. Eight patients were discovered in cancer screening, 9 in a voluntary setting, 14 at health checkups, 25 at follow-up of other diseases, and 32 cases by introduction from another hospital. Only 14 cases had been diagnosed with localized disease, but 5 cases were accompanied by regional lymph node metastasis. Furthermore, 12 cases showed infiltration into adjacent organs, and 24 cases had distant metastasis. Eighty-three cases were diagnosed by a pathological diagnosis. A surgical approach, chemotherapy, and radiotherapy were performed for 29, 35 patients, and 31 patients, respectively, while 17 patients received best supportive care.

Conclusion: The diagnosis of thymic carcinoma is still difficult, and this disease has a tragically rapid progression if when discovered during follow-up of other diseases. An innovative modality for the early detection of thymic carcinoma is needed in modern medical society.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-021-03620-8DOI Listing
May 2021

Autologous antigen-presenting cells efficiently expand transposon CAR-T cells with predominant memory phenotype.

Mol Ther Methods Clin Dev 2021 Jun 23;21:315-324. Epub 2021 Mar 23.

Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan.

The quality of chimeric antigen receptor (CAR)-T cell products, including the expression of memory and exhaustion markers, has been shown to influence their long-term functionality. The manufacturing process of CAR-T cells should be optimized to prevent early T cell exhaustion during expansion. Activation of T cells by monoclonal antibodies is a critical step for T cell expansion, which may sometimes induce excess stimulation and exhaustion of T cells. Given that transposon (PB)-based gene transfer could circumvent the conventional pre-activation of T cells, we established a manufacturing method of PB-mediated HER2-specific CAR-T cells (PB-HER2-CAR-T cells) that maintains their memory phenotype without early T cell exhaustion. Through stimulation of CAR-transduced T cells with autologous peripheral blood mononuclear cell-derived feeder cells expressing both truncated HER2, CD80, and 4-1BBL proteins, we could effectively propagate memory-rich, PD-1-negative PB-HER2-CAR-T cells. PB-HER2-CAR-T cells demonstrated sustained antitumor efficacy and debulked the HER2-positive tumors . Mice treated with PB-HER2-CAR-T cells rejected the second tumor establishment owing to the expansion of PB-HER2-CAR-T cells. Our simple and effective manufacturing process using PB system and genetically modified donor-derived feeder cells is a promising strategy for the use of PB-CAR-T cell therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omtm.2021.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047430PMC
June 2021

Heterozygous missense variant in TRPC6 in a boy with rapidly progressive infantile nephrotic syndrome associated with diffuse mesangial sclerosis.

Am J Med Genet A 2021 Jul 21;185(7):2175-2179. Epub 2021 Apr 21.

Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.

Transient receptor potential channel C6 encoded by TRPC6 is involved in slit diaphragm formation in podocytes, and abnormalities of the TRPC6 protein cause various glomerular diseases. The first identified pathogenic variant of TRPC6 was found to cause steroid-resistant nephrotic syndrome that typically developed in adulthood and then slowly led to end-stage renal disease, along with a renal pathology of focal segmental glomerulosclerosis. Here, we report a patient with rapidly progressing infantile nephrotic syndrome and a heterozygous missense TRPC6 variant. The patient, a 2-year-old Japanese boy, developed steroid-resistant nephrotic syndrome at age 11 months. His renal function deteriorated rapidly, and peritoneal dialysis was introduced at age 1 year and 6 months. His renal pathology, obtained at age 1 year and 1 month, was consistent with diffuse mesangial sclerosis (DMS). Clinical exome analysis and custom panel analysis for hereditary renal diseases revealed a reported heterozygous missense variant in TRPC6 (NM_004621.5:c.523C > T:p.Arg175Trp). This is the first report of a patient with a TRPC6-related renal disorder associated with DMS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.62216DOI Listing
July 2021

Development of non-viral, ligand-dependent, EPHB4-specific chimeric antigen receptor T cells for treatment of rhabdomyosarcoma.

Mol Ther Oncolytics 2021 Mar 5;20:646-658. Epub 2021 Mar 5.

Department of Pediatrics, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Ephrin type-B receptor 4 (EPHB4), expressed in tumors including rhabdomyosarcoma, is a suitable target for chimeric antigen receptor (CAR)-T cells. Ligand-independent activation of EPHB4 causes cell proliferation and malignant transformation in rhabdomyosarcoma, whereas ligand-dependent stimulation of EPHB4 induces apoptosis in rhabdomyosarcoma. Therefore, we hypothesized that ligand-based, EPHB4-specific CAR-T cells may kill rhabdomyosarcoma cells without stimulating downstream cell proliferation mechanisms. We developed novel CAR-T cells by targeting EPHB4 via EPHRIN B2, a natural ligand of EPHB4. The generation of EPHB4-CAR-T cells via (PB) transposon-based gene transfer resulted in sufficient T cell expansion and CAR positivity (78.5% ± 5.9%). PB-EPHB4-CAR-T cells displayed a dominant stem cell memory fraction (59.4% ± 7.2%) as well as low PD-1 expression (0.60% ± 0.21%) after 14 days of expansion. The PB-EPHB4-CAR-T cells inhibited EPHB4-positive tumor cells without activating cell proliferation downstream of EPHB4, even after multiple tumor re-challenges and suppressed tumor growth in xenograft-bearing mice. Therefore, PB-EPHB4-CAR-T cells possess a memory-rich fraction without early T cell exhaustion and show potential as promising therapeutic agents for treating rhabdomyosarcoma and other EPHB4-positive tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omto.2021.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985479PMC
March 2021

Investigation of risk factors associated with erythrocyte engraftment after ABO-incompatible hematopoietic stem cell transplantation.

Clin Transplant 2021 Jun 12;35(6):e14300. Epub 2021 May 12.

Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto, Japan.

ABO-incompatible hematopoietic stem cell transplantations (HSCTs) are widely practiced; however, the delay in erythrocyte engraftment can be problematic. While erythrocyte engraftment is usually indicated by an increase in reticulocyte levels without the need for erythrocyte transfusions, the disappearance of recipient-derived anti-A/B isoagglutinin and detection of donor-derived A/B antigens can also be used as other parameters. We conducted a retrospective analysis of 68 ABO-incompatible HSCTs, focusing on major and bidirectional mismatch. We analyzed known clinical risk factors associated with delayed erythrocyte engraftment using the three parameters (disappearance of anti-A/B isoagglutinin in recipient, detection of donor-derived A/B antigen, and reticulocyte levels >1%). Although the three parameters were well correlated, the results showed heterogeneity when analyzing the associated risk factors for delayed erythrocyte engraftment. In the analysis of all cases, the requirement for an HLA-matched platelet transfusion was a common risk factor. Furthermore, erythrocyte engraftment was slower in adults than in children. In adults, cytomegalovirus antigenemia was a risk factor for two parameters; however, in children, underlying disease was a common risk factor for all parameters. There is a complex relationship between erythrocyte engraftment and various factors related to HSCTs. Our results suggest that greater accuracy is possible by using analysis methods other than the measurement of reticulocyte levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ctr.14300DOI Listing
June 2021

Multi-institutional survey of cancer disparities in disabled patients in the region of northwestern Japan.

Int J Clin Oncol 2021 Jun 1;26(6):1009-1014. Epub 2021 Mar 1.

Division of Medical Oncology, Cancer Research Institute, Kanazawa University, 13-1, Takara-machi, Kanazawa, Ishikawa, 920-0934, Japan.

Background: Potential disparities between cancer patients with and without disabilities remained to be validate in Japan.

Methods: We surveyed retrospective data on hospital cancer registration as well as information on disability certificates obtained through the Hokushin Ganpro database. In total, 93,545 cancer patients in 10 principal hospitals covering the region of northwestern Japan were registered with the Hokushin Ganpro database between 2010 and 2015. The database included the following data: diagnosis date, cancer type, staging, treatment, cancer detection process, and possession of a disability certificate.

Results: We found that 2983 patients, which accounted for 3.2% of the total patients, had disabilities. No significant differences in gender, age at diagnosis, cancer stage distribution, and cancer incidence rates were observed between the disabled and non-disabled patients. Even though the proportion of early-stage cancer among disabled patients differed only slightly from that in non-disabled patients, early-stage cancer was more frequently diagnosed in patients with disabilities during their regular hospital visits than in those without disabilities, who had more opportunity for early cancer detection during cancer screening. According to in-house data reflecting treatment period and process from a single hospital, all 16 disabled patients treated with chemotherapy completed the treatment until disease progression or end of predetermined cycles.

Conclusion: These results indicate that deep disparities between cancer patients with and without disabilities are not apparent and that the disabled patients in the region of northwestern Japan receive appropriate hospital follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-021-01890-3DOI Listing
June 2021

Relationship between allergic sensitisation-associated single-nucleotide polymorphisms and allergic transfusion reactions and febrile non-haemolytic transfusion reactions in paediatric cases.

Blood Transfus 2021 Feb 3. Epub 2021 Feb 3.

Life Science Research Centre, Nagano Children's Hospital, Azumino, Japan.

Background: Allergic transfusion reactions (ATR) and febrile non-haemolytic transfusion reactions (FNHTR) are common transfusion-related adverse reactions; however, their pathogenesis remains unclear and it is difficult to predict their occurrence. Single-nucleotide polymorphisms (SNP) are related to the onset of various diseases and therapy-related adverse events; therefore, identification of SNP related to transfusion-related adverse reactions may help to elucidate the underlying mechanism and predict the onset of these reactions.

Materials And Methods: We retrospectively analysed the association between the onset of ATR or FNHTR and 22 allergic sensitisation-related SNP in 219 children (aged ≤20 years) who had haematological and oncological diseases and who had received transfusions of platelets and/or red blood cell concentrates.

Results: Among the 219 children, 105 had developed an ATR and/or FNHTR at least once. The patients who developed ATR frequently had a risk allele in rs6473223, while the patients who developed FNHTR frequently had a risk allele in rs10893845. Furthermore, patients who developed ATR accompanied by febrile symptoms also frequently had a risk allele in rs10893845, similar to patients who developed FNHTR.

Discussion: The results suggested that allergic sensitisation is associated with the onset of ATR and/or FNHTR in some patients. Although further prospective evaluation is necessary, analysis of these SNP might help to provide safer transfusion therapy by predicting patients at higher risk of transfusion-related adverse reactions and further clarifying the pathogenic mechanism underlying such reactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2450/2021.0230-20DOI Listing
February 2021

Relationship between placental weight and late-onset circulatory collapse.

Pediatr Int 2021 Jan 18. Epub 2021 Jan 18.

Department of Neonatology and Developmental Medicine, Shinshu University School of Medicine, Matsumoto, Japan.

Background: Late-onset circulatory collapse (LCC) is on an upward trend in Japan. It is a serious complication in preterm infants. The underlying pathophysiology is thought to be relative adrenal insufficiency and it is more likely to develop at young gestational age (GA) and in low birth weight (BW) infants. BW to placental weight ratio (BPR) is an index of pregnancy outcomes and early neonatal morbidity. We aimed to analyze the relationship between LCC and potential predicting factors including BPR.

Methods: This retrospective study included 261 singletons born before 32 weeks of gestation between 2007 and 2017. Perinatal data, including the placental weight and BPR, were collected from medical records and were assessed for their relationship with LCC. Propensity score analysis was performed, and matched factors were GA and BW.

Results: Sixty-seven infants (25.7%) had LCC (median GA 27.4 weeks). GA and BW differed significantly between the LCC and non-LCC groups (p <0.001, respectively). The placental weight and BPR of the LCC group were significantly lower than those of the non-LCC group, while Z-score of BPR did not differ significantly between both groups. After propensity score matching, there was a significant difference in the incidence of severe intraventricular hemorrhage (grades Ⅲ-Ⅳ) (p = 0.042), but no differences in BPR and Z-score of BPR between both groups.

Conclusion: In the propensity score analysis matched for GA and BW, there was no significant difference in perinatal factors including BPR between the LCC and non-LCC groups, except for incidence of severe intraventricular hemorrhage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ped.14609DOI Listing
January 2021

Characterization of the microbiota and chemical properties of pork loins during dry aging.

Microbiologyopen 2021 01 7;10(1):e1157. Epub 2021 Jan 7.

Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Hokkaido, Japan.

Dry aging (DA) allows for the storage of meat without packaging at 0 to 3°C for several weeks. It enhances the production of pleasant flavors, tenderness, and juiciness in meat. Due to the long storage period and roles of indigenous microbiota in the maturation of several meat products, the microbiota of DA meat is of interest in terms of microbial contributions and food hygiene but has not yet been characterized in detail. This study identified the microbiota of pork loins during DA using culturing and culture-independent meta-16S rRNA gene sequencing and elucidated its characteristics. The amounts of free amino acids and profiles of aroma-active compounds were also monitored by high-performance liquid chromatography and gas chromatography, respectively. The meta-16S rRNA gene sequencing revealed that Pseudomonas spp. generally dominated the microbiota throughout DA; however, the culturing analysis showed marked changes in the species composition during DA. Acinetobacter spp. were the second most dominant bacteria before DA in the culture-independent analysis but became a minor population during DA. The cell numbers of yeasts showed an increased tendency during DA, and Debaryomyces hansenii was the only microorganism isolated from all meat samples throughout DA. Well-known foodborne pathogens were not observed in two microbiota analyses. The amounts of free amino acids were increased by DA, and the number of aroma-active compounds and their flavor dilution values markedly changed during DA. Most microbial isolates showed positive reactions with proteolytic and lipolytic activities, suggesting their contribution to tenderness and aroma production in DA meats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mbo3.1157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914123PMC
January 2021

Orbital Epstein-Barr virus-related post-transplant lymphoproliferative disorder in a 13-year-old girl with cord blood transplantation.

Transpl Infect Dis 2020 Dec 2:e13536. Epub 2020 Dec 2.

Department of Pathology, Shinshu University School of Medicine, Matsumoto, Japan.

Epstein-Barr virus-associated post-transplant lymphoproliferative disorder (EBV-PTLD) is increasingly recognized as a life-threatening complication after transplantation. Most areas affected by EBV-PTLD are lymph nodes, with occasional reports of extranodal lesions such as the gastrointestinal tract and central nervous system; however, orbital regions are extremely rare. We report a case of EBV-PTLD in a cord blood transplant recipient with a tumor in the upper right eyelid. Ultimately, eye symptoms were the first signs of PTLD. Transplant physicians should consider the possibility of PTLD when encountering an orbital lesion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13536DOI Listing
December 2020

Autologous non-human primate model for safety assessment of transposon-mediated chimeric antigen receptor T cells on granulocyte-macrophage colony-stimulating factor receptor.

Clin Transl Immunology 2020 22;9(11):e1207. Epub 2020 Nov 22.

Department of Pediatrics Shinshu University School of Medicine Matsumoto Japan.

Objectives: Chimeric antigen receptor (CAR)-T cell therapy redirected to specific antigens on tumor cells is a promising immunotherapy strategy for various cancers. Most target antigens are also expressed on normal tissues at varying levels, and therefore, a considerable challenge in the field is determining safety profiles, including life-threatening off-tumor and off-target toxicities. The granulocyte-macrophage colony-stimulating factor receptor (hGMR) is a promising target for CAR T-cell therapy for a subset of acute myelocytic leukaemia, although it is also expressed on normal cells including monocytes, macrophages, CD34-positive haematopoietic cells and vascular endothelial cells. hGMR and other immune-related proteins are highly conserved between humans and cynomolgus macaques (). Therefore, in this study, we engineered cynomolgus T cells to express CAR molecules redirected to hGMR by (PB) transposon-based gene transfer and adoptively transferred autologous hGMR-CAR T cells into cynomolgus macaques.

Methods: We established PB-mediated human GMR (hGMR)-specific CAR T cells using cynomolgus peripheral blood mononuclear cells and transferred them into autologous individuals, and evaluated the potential toxicity related to hGMR-CAR T cells.

Results: hGMR-CAR T cells did not exert overt organ toxicities such as bone marrow suppression, monocytopenia and vasculitis, although they recognised and killed cynomolgus monocytes and macrophages .

Conclusion: Although our model did not simulate a tumor-bearing model, it supports the safety of hGMR-CAR T cells and demonstrates the usefulness of a non-human primate model to evaluate the safety of T-cell products by assessing off-tumor/off-target toxicity before clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cti2.1207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680920PMC
November 2020

Assessment of kidney function using inulin-based and estimated glomerular filtration rates before and after allogeneic hematopoietic stem cell transplantation in pediatric patients.

Pediatr Blood Cancer 2020 12 1;67(12):e28733. Epub 2020 Oct 1.

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.

Background: Accurate evaluation of kidney function before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is important for both informed decision making and detection of chronic kidney disease. However, to the best of our knowledge, no report has evaluated the glomerular filtration rate (GFR) in pediatric patients who underwent HSCT using the gold standard GFR measurement, as well as inulin-based GFR (iGFR).

Methods: We assessed iGFR before and after allo-HSCT to evaluate the impact of allo-HSCT on GFR in a prospective cohort study of 17 pediatric patients. We also assessed the accuracy and bias of the values of estimated GFR (eGFR) calculated using serum creatinine (Cr), cystatin C (CysC), beta-2 microglobulin (β MG), 24-h creatinine clearance (24hCcr), and the full chronic kidney disease in children (CKiD) index that combines Cr, CysC, and blood urea nitrogen-based equations with iGFR as a reference to identify the most reliable equation for GFR.

Results: There was no significant difference between the values before and after allo-HSCT. CKiD CysC-, 24hCcr-, and full CKiD-based values showed good within 30% (P30) accuracy (80.6%, 79.3%, and 80.6%, respectively), but only 24hCcr and full CKiD had good mean bias (8.5% and 8.9%, respectively) and narrow 95% limits of agreement (-32.2 to 52.7 mL/min/1.73 m and -29.3 to 47.4 mL/min/1.73 m , respectively) compared with the corresponding iGFR.

Conclusion: There was no significant impact of allo-HSCT on GFR in our cohort. The most reliable equations for pediatric patients with allo-HSCT were eGFR-24hCcr and eGFR-full CKiD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28733DOI Listing
December 2020

Hematopoietic stem cell transplantation in children and adolescents with nonremission acute lymphoblastic leukemia.

Pediatr Blood Cancer 2020 12 22;67(12):e28732. Epub 2020 Sep 22.

Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.

Background: The appropriateness of allogeneic hematopoietic stem cell transplantation (HSCT) in children and adolescents with leukemia in whom complete remission is not possible remains unclear. This retrospective analysis aimed to investigate the outcomes associated with HSCT, and the risks of HSCT in children and adolescents with nonremission acute lymphoblastic leukemia (ALL).

Procedure: Data from the Japan Society for Hematopoietic Cell Transplantation registry on 325 patients with nonremission ALL (aged <21 years, with blasts in the peripheral blood and/or bone marrow) who had undergone HSCT between January 2001 and December 2015 were evaluated. To assess survival, we developed a scoring system using significant adverse pre-HSCT variables.

Results: Overall, 247 patients died. The median length of follow up among survivors was 1145 days, and the 3-year overall survival was 22% (95% confidence interval [CI]: 18-27%). A low performance score, presence of >25% bone marrow blasts, T-cell phenotype, poor-risk or normal cytogenetics, and history of HSCT were predictors of a poor outcome. Patients scoring 0-1 (n = 109), 2 (n = 91), and 3-7 (n = 125) had a 3-year overall survival of 41% (95% CI: 31-51%), 21% (95% CI: 13-31%), and 7% (95% CI: 3-12%), respectively.

Conclusion: These results support HSCT in certain nonremission patients. Even in patients without complete remission, outcomes differed according to pre-HSCT factors. A scoring system could help determine the appropriateness of HSCT in children and adolescents with nonremission ALL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28732DOI Listing
December 2020

Association between pesticide usage during pregnancy and neonatal hyperbilirubinemia requiring treatment: the Japan Environment and Children's Study.

Pediatr Res 2021 May 5;89(6):1565-1570. Epub 2020 Aug 5.

Center for Perinatal, Pediatric, and Environmental Epidemiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.

Background: Maternal exposure to pesticides during pregnancy may cause oxidative hemolysis leading to neonatal hyperbilirubinemia. This investigation examined for associations between maternal use of pesticides or repellents during pregnancy and neonatal hyperbilirubinemia requiring phototherapy.

Methods: We used the dataset from the Japan Environment and Children's Study, a large national birth cohort study registered from January 31, 2011 to March 31, 2014. The fixed data of 61,751 live births were used to evaluate the presence of neonatal hyperbilirubinemia and potential confounding factors. We employed multiple logistic regression analysis to identify correlations between the frequency of maternal pesticide or repellent use during pregnancy and clinically relevant neonatal hyperbilirubinemia.

Results: After controlling for confounding factors, there were significant associations between neonatal hyperbilirubinemia necessitating phototherapy and the frequent use of indoor insecticide spray (OR 1.21, 95% CI 1.05-1.38). For spray- or lotion-type insect repellents, an opposite relationship was observed (more than a few times a week: OR 0.70, 95% CI 0.61-0.81, up to a few times a month: OR 0.84, 95% CI 0.78-0.91).

Conclusion: The frequent use of indoor insecticide spray during pregnancy showed an increased risk of neonatal hyperbilirubinemia requiring phototherapy, which was absent for spray- or lotion-type insect repellents.

Impact: The frequent use of indoor insecticide spray during pregnancy showed an increased risk of neonatal hyperbilirubinemia requiring phototherapy, which was absent for spray- or lotion-type insect repellents. This is the first study examining the effects of maternal exposure to pesticides or repellents on clinically relevant neonatal hyperbilirubinemia using a dataset from a nationwide birth cohort study. This large-scale Japanese cohort study revealed that the frequent use of indoor insecticide spray during pregnancy may increase the risk of neonatal hyperbilirubinemia requiring treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41390-020-1100-6DOI Listing
May 2021

Direct Delivery of CD19 CAR T Cells Has Potent Anti-tumor Activity against ALL Cells in CNS in a Xenograft Mouse Model.

Mol Ther Oncolytics 2020 Sep 26;18:37-46. Epub 2020 May 26.

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.

The anti-CD19 chimeric antigen receptor (CAR) T cells showed excellent effect against acute lymphoblastic leukemia (ALL) in bone marrow (BM) in clinical trials. However, it remains to be elucidated whether the CD19 CAR T cell therapy is effective for ALL cells in central nervous system (CNS) because the patients with isolated or advanced CNS disease were excluded from clinical trials of systemic intravenous (i.v.) delivery of CAR T cells. Therefore, the preclinical evaluation for the efficacy of CAR T cell therapy against ALL cells in CNS is essential for clinical application. We evaluated the effect and adverse reaction of CD19 CAR T cells against ALL in CNS using a xenograft mouse model by i.v. or intra-cerebroventricular (i.c.v.) delivery of CAR T cells. Injection of CD19 CAR T cells by i.v. had partial effects, whereas all CAR T i.c.v.-delivered mice had eliminated ALL in CNS. Although some CAR T i.c.v.-delivered mice showed transient changes of clinical symptoms during the first few days after treatment, none of CAR T i.c.v.-delivered mice displayed fatal adverse events. In this study, we demonstrated that direct delivery into CNS of CAR T cells is a possible therapeutic approach with the xenograft mouse model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omto.2020.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321814PMC
September 2020

Changes in laboratory findings in Parechovirus-A infection in nine neonates and infants.

Pediatr Int 2020 06;62(6):755-758

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ped.14197DOI Listing
June 2020

Transfusion outcome for volume- and plasma-reduced platelet concentrates for pediatric patients.

Transfus Apher Sci 2020 Aug 18;59(4):102776. Epub 2020 May 18.

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.

Background And Objectives: Plasma reduction in platelet concentrate (PC) products has been reported to prevent large volume load and transfusion-related adverse reactions (TRARs). However, volume reduction might be associated with a poor transfusion response because of a deterioration in platelet (PLT) quality. Because PLT quality control and transfusion responses for recently washed PCs using PLT additive solutions are superior, we investigated the clinical safety and transfusion efficacy of volume-reduced washed PCs in pediatric patients.

Materials And Methods: We prepared a simplified resuspended PC product (RPC) as a washed PC. Regular RPC (R-RPC) included equivalent volumes of bicarbonate Ringer's solution and anticoagulant citrate dextrose solution A (BRS-A) as the resuspension solution. Half RPC (H-RPC) was prepared by adding a half volume of BRS-A. Twenty-four pediatric patients were scheduled for transfusions with R-RPC and H-RPC up to 4 times. R-RPC was transfused 42 times into 24 patients. H-RPC was transfused 41 times into 23 patients.

Results: Neither product was observed to cause TRARs. Although the calculated PLT recovery for H-RPC was significantly reduced, the posttransfusion corrected count increment (24 h) did not differ. Moreover, similar results were observed for vital signs during transfusion.

Conclusion: Volume-reduced washed PC can be transfused without causing TRARs, differences in vital signs, or inferior transfusion responses. Volume-reduced washed PC also provides the advantages of shortened transfusion times and reduced volume loads. Although a standard technique for stable resuspension is necessary, volume-reduced washed PC may be a beneficial option for children, including neonates, or individuals with cardiovascular or renal problems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transci.2020.102776DOI Listing
August 2020

Trends in gastroesophageal reflux disease in Japanese children and adolescents.

Pediatr Int 2020 Nov 4;62(11):1269-1274. Epub 2020 Nov 4.

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.

Background: Although the prevalence of gastroesophageal reflux disease (GERD) has been increasing in Japan, little is known about the prevalence and severity of GERD in pediatric patients. This study compared the prevalence and severity of endoscopically proven GERD in pediatric patients seen at an endoscopy center in Japan over a 15-year period.

Methods: This was a retrospective chart review of Japanese children aged 5-18 years undergoing esophagogastroduodenoscopy for upper gastrointestinal symptoms or anemia between 2005 and 2019. The prevalence and severity of reflux esophagitis and endoscopic Barrett's esophagus were compared between the periods 2005-2012 and 2013-2019.

Results: A total of 564 patients were evaluated: 315 from 2005 to 2012 (mean ± SD) age 13.8 ± 3.0 (range, 5-18 years; 147 boys; and 249 from 2013 to 2019 (mean ± SD) 14.7 ± 2.8 (range, 5-18) years; 108 boys. Demographics and clinical features were similar between the two groups. The proportion with erosive esophagitis or endoscopic Barrett's esophagus increased significantly between the two periods (9.8% to 18.1% for GERD, P = 0.0045 and 2.5% to 9.6% for Barrett's esophagus, P = 0.0003). The proportion of GERD patients with endoscopic Barrett's esophagus also significantly increased between the two periods (24/45 [53.3%]) vs (8/31 [25.8%]), P = 0.017].

Conclusion: The prevalence and severity of endoscopically proven GERDs has significantly increased over the past 15 years at an endoscopy center in Japan. Detailed population-based studies are needed to assess whether this is occurring throughout Japan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ped.14324DOI Listing
November 2020

Heart rate variability in the course of chemotherapy and haematopoietic stem cell transplantation for peadiatric patients with haematological malignancies.

Cardiol Young 2020 Jul 29;30(7):967-974. Epub 2020 May 29.

Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Nagano, Japan.

Background: High-dose chemotherapy and haematopoietic stem cell transplantation are essential for patients with paediatric haematologic diseases, although cardiotoxicity remains a concern. Heart rate variability analysis can evaluate autonomic nervous function interactions with cardiac function.

Objective: This study aimed to characterise heart rate variability differences between patients undergoing chemotherapy and controls, and the effects of haematopoietic stem cell transplantation on the autonomic nervous system in patients with haematological malignancies.

Methods: Nineteen patients (11 male, median age: 11.6 years) who received conventional chemotherapy followed by transplantation and 19 non-transplant patients (10 male, median age: 11.5 years) receiving chemotherapy only between 2006 and 2018 for haematological malignancies were retrospectively enrolled. Data from 24-hour Holter monitoring were recorded after chemotherapy and before and after transplantation. Heart rate variability was analysed in patients and 32 matched normal controls.

Results: There were significant differences between patients and normal controls in all heart rate variability analysis parameters apart from coefficient of variation of RR interval and standard deviation of the average normal RR interval for all 5-minute segments during sleeping. There was a significant difference in the cumulative anthracycline dose and heart rate variability during sleep between the non-transplant and pre-transplant groups. We observed no remarkable differences in time-domain analysis parameters between before and after transplantation, although the low-frequency component of power-spectrum analysis during awake hours was significantly decreased after transplantation.

Conclusion: Conventional chemotherapy for paediatric haematologic diseases may be a risk factor for autonomic dysfunction. Further declines in heart rate variability after transplantation appear minor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1047951120001298DOI Listing
July 2020

Long-term outcomes of children with extracutaneous juvenile xanthogranulomas in Japan.

Pediatr Blood Cancer 2020 07 8;67(7):e28381. Epub 2020 May 8.

Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Japan.

Background: Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytosis in children. The mortality and morbidity of JXG with extracutaneous lesions remain unclear.

Methods: Data of patients aged < 18 years who were diagnosed with JXG between 2001 and 2010 were retrospectively collected through a nationwide survey.

Results: Twenty patients (11 male and nine female) had extracutaneous lesions. The median observation time was 10 years (range, 0-17). Six patients presented with symptoms at birth. The median age at diagnosis was 8.5 months (range, 0 month-13 years). Fifteen patients underwent treatment for JXG, including chemotherapy (n = 11), and five did not receive treatment. All patients except one survived; 17 were disease-free and two survived with disease. One newborn-onset patient with liver, spleen, and bone marrow involvement died of the disease. Permanent sequelae included central diabetes insipidus, growth hormone deficiency, and panhypopituitarism detected at diagnosis in three, one, and two patients, respectively. Four patients had visual impairment (optic nerve compression and intraocular invasion in two each), three had epilepsy, one had mental retardation, and one had a skin scar. Eight patients who had intracranial lesions were older at diagnosis, and had a higher frequency of disease-related comorbidities and permanent sequelae than those without intracranial involvement.

Conclusions: Patients with extracutaneous JXG had good outcomes, although those with intracranial lesions had serious permanent sequelae. Effective and safe treatment regimens for patients with intracranial JXG need to be developed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28381DOI Listing
July 2020

Impact of immunophenotypic characteristics on genetic subgrouping in childhood acute lymphoblastic leukemia: Tokyo Children's Cancer Study Group (TCCSG) study L04-16.

Genes Chromosomes Cancer 2020 10 16;59(10):551-561. Epub 2020 Jul 16.

Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development (Research Institute, National Center for Child Health and Development, NCCHD), Tokyo, Japan.

Immunophenotyping was performed in 1044 consecutive childhood acute lymphoblastic leukemia (ALL) patients enrolled in the Tokyo Children's Cancer Study Group L04-16 trial, revealing novel findings associated with genetic abnormalities. In addition to TCF3-PBX1 and MEF2D fusions, the CD10 subtype of KMT2A-MLLT3-positive ALL frequently exhibited the cytoplasmic-μ pre-B ALL immunophenotype. Although ETV6-RUNX1 was significantly correlated with myeloid antigen expression, more than half of patients expressed neither CD33 nor CD13, while the CD27 /CD44 immunophenotype was maintained. Expression of CD117 and CD56 in B-cell precursor-ALL was limited to certain subtypes including ETV6-RUNX1 and KMT2A-MLLT3. Besides BCR-ABL1, CRLF2, hyperdiploidy, and hypodiploidy, CD66c was also expressed in Ph-like kinase fusion-, PAX5 fusion-, and DUX4 fusion-positive ALL, but not in MEF2D fusion-positive ALL, indicating constant selectivity of CD66c expression. In T-ALL, SIL-TAL1-positive patients were likely to exhibit a more mature immunophenotype. Expression of CD21 and CD10 was not rare in T-ALL, while lack of CD28 was an additional feature of early T-cell precursor-ALL. Considering the immunophenotype as a prognostic maker, MEF2D fusion-positive ALL with CD5 expression may be associated with a poorer prognosis in comparison with those lacking CD5 expression. In cases with characteristic marker expression, the presence of certain fusion transcripts could be predicted accurately.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gcc.22858DOI Listing
October 2020

Impact of infliximab administration before plasma exchange therapy on patients with Kawasaki disease.

Ther Apher Dial 2020 Dec 7;24(6):718-724. Epub 2020 Mar 7.

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.

Plasma exchange is a therapeutic option in refractory Kawasaki disease (KD). However, the effects of other immunosuppressive treatments on plasma exchange therapy have not been studied. We investigated the effect of infliximab on plasma exchange in KD as well as on the outcome in patients with KD. We studied 16 patients with intravenous immunoglobulin-resistant KD who finally underwent plasma exchange. The patients were divided into two groups: patients who received infliximab before plasma exchange (infliximab group) and patients who did not (non-infliximab group). The infliximab group showed a lesser median number of required total plasma exchange sessions (P = .002) and higher change and reduction rates in C-reactive protein before and after the first plasma exchange (both P = .027) than that of the non-infliximab group. Infliximab administered before plasma exchange reduced the number of total plasma exchange sessions and improved the plasma exchange efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1744-9987.13486DOI Listing
December 2020

Usefulness of Continuous Glucose Monitoring for Prevention and Early Detection of Hypoglycemia Caused by a Ketogenic Diet and Late Dumping Syndrome.

Pediatr Neurol 2020 04 26;105:65-66. Epub 2019 Dec 26.

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2019.12.002DOI Listing
April 2020

Thyroid tumor surveillance using ultrasound in childhood cancer survivors.

Pediatr Int 2020 May;62(5):562-568

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.

Background: The optimal method for thyroid cancer screening in childhood cancer survivors (CCSs) who received radiation involving the thyroid gland is still debated. We describe a case series of ultrasound surveillance for thyroid tumor in CCSs in our institute.

Methods: We conducted thyroid tumor surveillance for CCSs with a history of radiation therapy involving the thyroid. The basic screening method was palpation. Thyroid ultrasound was also performed for patients who agreed after its benefits and risks were explained to them. We surveyed CCSs who visited the long-term follow-up outpatient clinic in our institution between October 2014 and September 2018.

Results: Of 82 CCSs who visited our institution during the study period, 44 were eligible for inclusion. None had a mass identified by palpation. Thyroid ultrasound was performed in 39 CCSs, and we identified thyroid nodules in 27. Four patients had a nodule with malignant echo features. Two of these cases received biopsies, and one patient was ultimately diagnosed with an early stage thyroid carcinoma.

Conclusions: Childhood cancer survivors irradiated in the thyroid had a higher prevalence of thyroid nodules than the general population. Ultrasound screening contributed to early detection of impalpable thyroid cancer and enabled us to perform minimal surgery. Thus, ultrasound appears to be a useful option for secondary thyroid cancer screening. The thyroid tumor surveillance modality should be considered according to the individual case, and the patient must receive a clear explanation of the benefits and risks. These results could help doctors consider how to screen for secondary thyroid cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ped.14179DOI Listing
May 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

Comparative analysis of graft-versus-host disease prophylaxis with tacrolimus in combination with methylprednisolone or methotrexate after umbilical cord blood transplantation.

Int J Hematol 2020 May 18;111(5):702-710. Epub 2020 Jan 18.

Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.

Post-transplant early immune disorders and engraftment failure/delay are major issues in unrelated umbilical cord blood transplantation (UCBT). We evaluated graft-versus-host disease (GVHD) prophylaxis approaches after UCBT by comparing UCBT outcomes with GVHD prophylaxis using tacrolimus plus methylprednisolone (Tac/mPSL, n = 32) to that with Tac plus methotrexate (Tac/MTX, n = 31) at a single pediatric transplantation center. The 30-day cumulative incidence rates of neutrophil engraftment and median neutrophil engraftment times in the Tac/mPSL and Tac/MTX groups were 70.1% and 90.3% and 19 and 17 days, respectively (p = 0.09). Pre-engraftment immune reactions (PIR) and acute GVHD were improved with Tac/MTX; PIR incidence (p = 0.020) and cumulative incidence of 100-day acute GVHD (grade II-IV, 38.7% vs 68.8%, p = 0.045; grade III-IV, 9.7% vs 34.4%, p = 0.021) were significantly lower in the Tac/MTX group than in the Tac/mPSL group. However, the incidence rates of relapse (p = 0.921) and cytomegalovirus reactivation (p = 0.908), and the estimated overall (p = 0.87) and event-free survival (p = 0.88) were comparable between the two groups. These data indicate that GVHD prophylaxis with Tac/MTX is associated with favorable results, including reduced PIR and acute GVHD incidence after UCBT, without adverse effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-020-02826-9DOI Listing
May 2020