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Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT), and stratification of the high-risk group before transplantation is significant. Serum autotaxin (ATX) levels have been reported to increase in patients with liver fibrosis caused by metabolic inhibition from liver sinusoidal endothelial cells. Considering that the pathophysiology of VOD/SOS begins with liver sinusoidal endothelial cell injury, an increase in serum ATX levels may precede the onset of VOD/SOS. A retrospective study with 252 patients, including 12 patients with VOD/SOS, who had received allo-HCT was performed. The cumulative incidence of VOD/SOS was higher in the group with serum ATX levels before conditioning (baseline ATX) above the upper reference limit (high ATX group, p < 0.001), and 1-year cumulative incidences were 22.7% (95% confidence interval [95%CI], 3.1-42.4%) and 3.5% (95%CI, 1.1-5.8%), respectively. In the multivariate analysis, elevated baseline ATX was identified as an independent risk factor for VOD/SOS development and showed an additive effect on the predictive ability of known risk factors. Furthermore, the incidence of VOD/SOS-related mortality was greater in the high ATX group (16.7% vs. 1.3%; p = 0.005). Serum ATX is a potential predictive marker for the development of VOD/SOS.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Humanos , Enfermedad Veno-Oclusiva Hepática/epidemiología , Enfermedad Veno-Oclusiva Hepática/etiología , Estudios Retrospectivos , Células Endoteliales , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Factores de RiesgoRESUMEN
Myelodysplastic syndrome (MDS) is well known to be complicated by systemic inflammatory autoimmune disease (SIADs). However, it remains unclear how the prognosis after allogenic hematopoietic stem cell transplantation (allo-HSCT) in patients with MDS is impacted by SIADs that occur before allo-HSCT. Therefore, we hypothesized that SIADs before allo-HSCT may be a risk factor for negative outcomes after allo-HSCT in patients with MDS. We conducted a single-center, retrospective, observational study of sixty-nine patients with MDS or chronic myelomonocytic leukemia who underwent their first allo-HCT. Fourteen of the patients had SIADs before allo-HSCT. In multivariate analysis, the presence of SIADs before allo-HSCT was an independent risk factor for overall survival (HR, 3.36, 95% confidence interval: 1.34-8.42, p = 0.009). Endothelial dysfunction syndrome was identified in five of 14 patients with SIADs who required immunosuppressive therapy or intensive chemotherapy, and notably, all patients with uncontrollable SIADs at allo-HSCT developed serious endothelial dysfunction syndrome and died in the early phase after allo-HSCT. The development of SIADs in the context of MDS is thought to reflect the degree of dysfunction of hematopoietic cells in MDS and suggests a higher risk of disease progression. In addition, MDS patients with SIADs before allo-HSCT are considered to be at higher risk of endothelial dysfunction syndrome because of preexisting vascular endothelial dysfunction due to SIADs. In conclusion, SIADs before allo-HSCT constitute an independent risk factor for death in MDS patients undergoing allo-HSCT.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mielomonocítica Crónica , Síndromes Mielodisplásicos , Humanos , Femenino , Masculino , Leucemia Mielomonocítica Crónica/mortalidad , Leucemia Mielomonocítica Crónica/terapia , Síndromes Mielodisplásicos/terapia , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/complicaciones , Persona de Mediana Edad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Adulto , Anciano , Enfermedades Autoinmunes/mortalidad , Enfermedades Autoinmunes/terapia , Trasplante Homólogo/efectos adversos , Aloinjertos , Tasa de SupervivenciaRESUMEN
OBJECTIVES: Impaired B-cell reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT) contributes to the pathogenesis of chronic graft-versus-host disease (cGVHD). Therefore, methods to consistently achieve effective B cell lymphogenesis are required. We assessed the long-term effects of posttransplantation cyclophosphamide (PTCy) use on immune reconstitution in clinical settings, an emerging strategy to suppress allogeneic immunological inflammation early after allo-HCT and prevent subsequent GVHD. METHODS: We comprehensively analyzed peripheral immune cell subsets and measured serum immunoglobulin G (IgG) or cytokine levels in 39 patients who survived for >1 year after allo-HCT. RESULTS: The absolute counts of B1 and IgM memory B cells were significantly lower in patients with severe cGVHD than in those without. The absolute count and percentage (among total CD19+ B cells) of switched memory B cells and serum IgG levels were significantly higher in patients transplanted with PTCy than in those transplanted with conventional GVHD prophylaxis. Interestingly, increased percentages of switched memory B cells and serum IgG levels were observed only in patients transplanted with PTCy and not in those transplanted with umbilical cord blood. CONCLUSIONS: PTCy administration can mediate favorable memory B-cell reconstitution long after allo-HCT and may therefore suppress cGVHD.
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INTRODUCTION: The graft-versus-leukemia effect of HLA-B leader dimorphism, i.e. methionine (M) or threonine (T) at position -21 of the leader sequence, has been observed in HLA-haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide (PTCy-haplo). However, the biological mechanism has been unclear, and the contributions of HLA-B leader genotype to risk reduction of relapse might be dependent on posttransplant cyclophosphamide (PTCy) doses. METHODS: To investigate whether the effect of HLA-B leader dimorphism was modified by the PTCy dose, we retrospectively analyzed 99 patients who received PTCy-haplo. RESULTS: In the low-dose PTCy group, the patient M+ HLA-B leader genotype did not significantly affect the cumulative incidence of relapse (CIR) but negatively impacted the overall survival (OS) compared to the M- genotype. In contrast, in the high-dose PTCy group, patients with the M+ genotype had a decreased CIR, but no significant difference in the OS was observed between patients with the M+ and M- genotypes. Regardless of PTCy doses, the patient M+ genotype had detrimental effects on nonrelapse mortality. CONCLUSION: Our findings suggest that the effect of the patient HLA-B leader genotype is modified by the PTCy dose, providing immunological insight into the PTCy dosage and supporting further studies to investigate the underlying mechanisms.
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Blastobotrys is a genus of rare yeast that is increasingly recognized as a cause of fungal infections in humans. However, there have been no reports of fungal infections in humans caused by Blastobotrys mokoenaii. We describe a case of invasive fungal infection (IFI) caused by B. mokoenaii in an immunocompromised patient with acute myeloid leukemia (AML). A 46-year-old man with relapsed/refractory AML underwent a second allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBSCT) during remission. The patient had prolonged neutropenia and received systemic steroid therapy for graft-versus-host disease before the second allo-PBSCT. Uncommon yeast was isolated from the blood cultures obtained on day 4. We initially suspected that the uncommon yeast was Trichosporon spp. based on its morphology. However, unlike Trichosporon spp., in vitro antifungal susceptibility tests showed that this yeast isolate was resistant to micafungin, caspofungin, voriconazole, itraconazole, and fluconazole. We performed DNA sequencing and identified it as B. mokoenaii. B. mokoenaii was persistently isolated from blood cultures taken during combination therapy with liposomal amphotericin B and voriconazole. The patient died of multiorgan failure on day 24. B. mokoenaii can cause severe IFI in immunocompromised patients; however, it may not be correctly identified by routine clinical microbiology testing in a hospital laboratory and DNA sequencing is useful for diagnosis.
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Health surveys to assess adverse events after peripheral blood stem cell harvest (PBSCH) have conventionally been conducted by phone, but phone calls are suboptimal for conducting frequent surveys. We developed a web-based application (donor app) that enables donors to inform healthcare professionals (HCPs) of their health status as an electronic patient-reported outcome (ePRO). In this prospective observational study, we compared the usefulness of this donor app to phone calls for conducting health surveys. App users reported ePRO daily, and patients called by HCPs reported their health status at least once a week when called. The observation period was from the first administration of granulocyte colony-stimulating factor to the first follow-up visit after PBSCH, excluding the hospitalization period. Each group consisted of eight donors with a median age of 32 years (range: 19-58). Nine (56.3%) were female. There were eight related donors in the phone call group and four in the donor app group. During the observation period, HCPs obtained health status reports more frequently from app users than from phone call recipients (mean proportion of days with reports made during the observation period, 27.0% vs 53.5%; p<0.05). Average time spent by the HCPs for one follow-up and total follow-ups were both significantly shorter when the donor app was used. There were no differences in donor burden or satisfaction with donation. Our study suggests that use of a donor app could provide more detailed health survey data without increasing the burden on donors and HCPs.
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Encuestas Epidemiológicas , Internet , Células Madre de Sangre Periférica , Humanos , Adulto , Femenino , Masculino , Persona de Mediana Edad , Adulto Joven , Estudios ProspectivosRESUMEN
BACKGROUND AIMS: CD4+CD25+CD127lo regulatory T cells (Tregs) are responsible for maintaining immune homeostasis. Tregs can be rendered defective and deficient as a result of the immune imbalance seen in lung injury, and such dysfunction can play a major role in continued tissue inflammation. The authors hypothesized that adoptive therapy with healthy allogeneic umbilical cord blood (UCB)-derived Tregs may be able to resolve inflammation. RESULTS: Ex vivo-expanded UCB Tregs exhibited a unique phenotype with co-expression of CD45RA+CD45RO+ >80% and lung homing markers, including CD49d. UCB Tregs did not turn pathogenic when exposed to IL-6. Co-culture with increasing doses of dexamethasone led to a synergistic increase in UCB Treg-induced apoptosis of conventional T cells (Tcons), which translated into significantly higher suppression of proliferating Tcons, especially at a lower Treg:Tcon ratio. Multiple injections of UCB Tregs led to their preferential accumulation in lung tissue in an immune injury xenogenic model. A significant decrease in lung resident cytotoxic CD8+ T cells (P = 0.0218) correlated with a sustained decrease in their systemic distribution compared with controls (P < 0.0001) (n = 7 per arm) as well as a decrease in circulating human soluble CD40 ligand level (P = 0.031). Tissue architecture was preserved in the treatment arm, and a significant decrease in CD3+ and CD8+ burden was evident in immunohistochemistry analysis. CONCLUSIONS: UCB Treg adoptive therapy is a promising therapeutic strategy for treatment of lung injury.
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Trasplante de Células Madre Hematopoyéticas , Lesión Pulmonar , Neumonía , Humanos , Linfocitos T Reguladores , Sangre Fetal , Linfocitos T CD8-positivos , Inflamación/terapia , Antígenos Comunes de LeucocitoRESUMEN
CD19-directed chimeric antigen receptor (CAR) T-cell therapy has been widely used and is highly effective for B-cell lymphoid malignancies. Immune-mediated adverse effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occur in the acute phase and are monophasic after CAR T-cell therapy. However, late-onset inflammatory and neurological toxicities have not been well studied. We encountered a patient with recurrent late-onset inflammatory toxicities and progressive dysautonomia after CD19-directed CAR T-cell therapy. A 69-year-old man was treated with CD19-directed CAR T-cell therapy for transformed follicular lymphoma. Triphasic inflammation with stomatitis, cytopenia, and noninfectious pneumonia was first observed 7 months after CAR T-cell infusion. Progressive dysautonomia was also observed and eventually fatal. Residual CAR T cells, predominantly central memory CD4+ cells, were detectable in peripheral blood approximately 1 year after CAR T-cell infusion. The cytokine profile with the lack of tumor necrosis factor-α, interferon-γ, and interleukin-1ß elevation in the peripheral blood and cerebrospinal fluid was inconsistent with that of typical CRS or ICANS. The persistence of central memory CD4+ CAR T cells might be associated with unique manifestations of late-onset immune-mediated adverse effects. More cases should be accumulated to elucidate the mechanism and establish the optimal management strategy of late-onset immune-mediated toxicities previously unrecognized.
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Linfoma Folicular , Linfoma no Hodgkin , Receptores Quiméricos de Antígenos , Masculino , Humanos , Anciano , Recurrencia Local de Neoplasia , Inmunoterapia Adoptiva/efectos adversos , Linfocitos T CD4-Positivos , Antígenos CD19RESUMEN
Sinusoidal obstruction syndrome (SOS) is a fatal complication after hematopoietic stem cell transplantation (HSCT). Only a few complications after HSCT have been reported as risk factors for SOS, including sepsis. Here, we report the case of a 35-year-old male diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent peripheral blood HSCT from a human leukocyte antigen-matched unrelated female donor in remission. Graft-versus-host disease prophylaxis contained tacrolimus, methotrexate, and low-dose anti-thymoglobulin. The patient was treated with methylprednisolone for engraftment syndrome from day 22. On day 53, he presented worsening fatigue, breathlessness, and abdominal pain in the right upper quadrant that had persisted for 4 days. Laboratory tests showed severe inflammation, liver dysfunction, and positive for Toxoplasma gondii PCR. He died on day 55. An autopsy showed SOS and disseminated toxoplasmosis. Hepatic infection with T. gondii was identified in zone 3 of the liver, which overlapped with the pathological features of SOS. In addition, the timing of the exacerbation of hepatic dysfunction coincided with the onset of systemic inflammatory symptoms and T. gondii reactivation. This rare case of toxoplasmosis is the first to suggest that hepatic infection with T. gondii is strongly associated with SOS after HSCT.
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Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is being increasingly recognized as a severe complication that contributes to poor prognoses among patients with COVID-19. However, little is known regarding the clinical course of CAPA with hematological malignancies, especially after allogeneic hematopoietic stem cell transplantation (HSCT). A 29-year-old woman was diagnosed with proven CAPA with an Aspergillus fumigatus identified by cultures of bronchoalveolar lavage and lung biopsy four years after haploidentical HSCT for acute myelogenous leukemia. She had been taking oral prednisolone for bronchiolitis obliterans syndrome that developed after HSCT. Although prolonged RT-PCR positivity for SARS-CoV-2 (133 days after the onset of COVID-19) without shedding of viable virus was observed, the COVID-19 was treated with favipiravir, remdesivir, dexamethasone, and enoxaparin. However, the CAPA did not respond to combination therapy, which included triazole (voriconazole, itraconazole, posaconazole) and echinocandin (caspofungin, micafungin), even though the Aspergillus fumigatus isolate was found to be susceptible to these agents in vitro. Nevertheless, a total of 16 weeks of liposomal amphotericin B (L-AMB) therapy led to a favorable response, and the patient was discharged from the hospital on day 213. This case provided essential experience of CAPA treated with L-AMB in a recipient with chronic respiratory disease after HSCT.
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Síndrome de Bronquiolitis Obliterante , COVID-19 , Trasplante de Células Madre Hematopoyéticas , Aspergilosis Pulmonar , Femenino , Humanos , Adulto , Antifúngicos/uso terapéutico , COVID-19/complicaciones , SARS-CoV-2 , Aspergilosis Pulmonar/complicaciones , Aspergilosis Pulmonar/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Aspergillus fumigatusRESUMEN
Although ropeginterferon alfa-2b has recently been clinically applied to myeloproliferative neoplasms with promising results, its antitumor mechanism has not been thoroughly investigated. Using a leukemia model developed in immunocompetent mice, we evaluated the direct cytotoxic effects and indirect effects induced by ropeginterferon alfa-2b in tumor cells. Ropeginterferon alfa-2b therapy significantly prolonged the survival of mice bearing leukemia cells and led to long-term remission in some mice. Alternatively, conventional interferon-alpha treatment slightly extended the survival and all mice died. When ropeginterferon alfa-2b was administered to interferon-alpha receptor 1-knockout mice after the development of leukemia to verify the direct effect on the tumor, the survival of these mice was slightly prolonged; nevertheless, all of them died. In vivo CD4+ or CD8+ T-cell depletion resulted in a significant loss of therapeutic efficacy in mice. These results indicate that the host adoptive immunostimulatory effect of ropeginterferon alfa-2b is the dominant mechanism through which tumor cells are suppressed. Moreover, mice in long-term remission did not develop leukemia, even after tumor rechallenge. Rejection of rechallenge tumors was canceled only when both CD4+ and CD8+ T cells were removed in vivo, which indicates that each T-cell group functions independently in immunological memory. We show that ropeginterferon alfa-2b induces excellent antitumor immunomodulation in hosts. Our finding serves in devising therapeutic strategies with ropeginterferon alfa-2b.
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Leucemia , Trastornos Mieloproliferativos , Neoplasias , Animales , Linfocitos T CD8-positivos , Inmunomodulación , Interferón-alfa/farmacología , Interferón-alfa/uso terapéutico , Leucemia/tratamiento farmacológico , Ratones , Neoplasias/tratamiento farmacológico , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéuticoRESUMEN
Monoclonal gammopathy of undermined significance (MGUS) is usually asymptomatic, and untreated follow-up is the standard treatment. However, MGUS progresses to multiple myeloma or related malignancy at a frequency of 1.5% per year. It is sometimes difficult to diagnose the progression of the disease via usual examinations. We herein report a case wherein rapid renal dysfunction led to a diagnosis of disease progression to multiple myeloma in a patient with MGUS that was asymptomatic for a long time. A 66-year-old woman developed rapid renal dysfunction requiring continuous hemodiafiltration 8 years after the diagnosis of IgA-κ type MGUS. A complete examination led to the diagnosis of IgA-κ type multiple myeloma. Chemotherapy was not effective, and she died due to sepsis on the 19th day of admission. A pathological autopsy revealed systemic amyloidosis and multiple abscesses positive for Staphylococcus aureus. An abnormal free light chain κ/λ ratio and M protein other than IgG are reportedly risk factors of disease progression of MGUS. In cases with these risk factors, it is important to always keep in mind the possibility of disease progression and to monitor the patient carefully for an early diagnosis.
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Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Gammopatía Monoclonal de Relevancia Indeterminada , Mieloma Múltiple , Paraproteinemias , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Cadenas Ligeras de Inmunoglobulina , Gammopatía Monoclonal de Relevancia Indeterminada/complicaciones , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnósticoRESUMEN
There is currently no evidence that a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine might be associated with the development of autoimmune hemolytic anemia or disease progression in patients with mature B-cell neoplasm. Our patient was a 71-year-old man with indolent mature B-cell neoplasm who had been monitored for many years without treatment. After receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine, he developed severe warm autoimmune hemolytic anemia. Although steroid therapy improved his anemia, he continued to develop IgM-monoclonal gammopathy, renal insufficiency, and splenomegaly. He was diagnosed with splenic marginal zone lymphoma after undergoing splenectomy. The splenectomy improved the patient's symptoms. We assessed his SARS-CoV-2 specific antibody response, but the patient's serologic response to the vaccine was impaired. In patients with mature B-cell neoplasm, a non-specific immune response after vaccination might be associated with paraneoplastic syndromes.
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Anemia Hemolítica Autoinmune , Vacunas contra la COVID-19 , COVID-19 , Leucemia Linfocítica Crónica de Células B , Linfoma de Células B , Paraproteinemias , Neoplasias del Bazo , Anciano , Humanos , Masculino , Anemia Hemolítica Autoinmune/etiología , Anemia Hemolítica Autoinmune/complicaciones , Vacuna BNT162 , COVID-19/complicaciones , Vacunas contra la COVID-19/efectos adversos , Inmunoglobulina M , Leucemia Linfocítica Crónica de Células B/complicaciones , Linfoma de Células B/tratamiento farmacológico , Paraproteinemias/complicaciones , SARS-CoV-2 , Neoplasias del Bazo/complicaciones , Vacunas de ARNmRESUMEN
The phase 3 ICARIA-MM trial showed that the addition of isatuximab improved the progression-free survival compared with pomalidomide/dexamethasone. However, the safety and efficacy of isatuximab for end-stage renal failure remains unclear. A 67-year-old man who started hemodialysis 5 years ago for diabetic nephropathy was diagnosed with International Staging System stage III multiple myeloma (MM) of IgD-λ type 3 years ago. After receiving a total of 7 treatment regimens, his free light chain (FLC) λ level increased from 419 to 2,070 mg/L, indicating progressive disease. Twelve days after starting isatuximab plus pomalidomide (3 mg daily) and dexamethasone (IsaPd), his FLC λ level rapidly decreased to 412 mg/L. The patient has now completed 7 courses of IsaPd with no adverse events, including infusion reactions and neutropenia. Isatuximab requires a lower dilution volume than daratumumab and can be safely and effectively administered to hemodialysis-dependent MM patients.
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Mieloma Múltiple , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/efectos adversos , Humanos , Masculino , Mieloma Múltiple/tratamiento farmacológico , Diálisis RenalRESUMEN
Chylothorax is a rare clinical sign in patients with diffuse large B-cell lymphoma (DLBCL), which is often challenging to manage and has a poor prognosis. We report the case of a 59-year-old woman who presented with right pleural effusion at the time of DLBCL diagnosis. Lymphadenopathy rapidly improved in response to chemotherapy. However, the pleural effusion progressed and was identified as chylothorax by thoracentesis. Because attempts to manage the condition with fasting and central venous nutrition were unsuccessful, we performed ultrasound-guided intranodal lipiodol lymphangiography from the inguinal lymph node. Although leak sites were not detected, the pleural effusion markedly improved on the day after the examination and resolved after 2 months. Lymphangiography is a minimally invasive examination with few complications. It contributes not only to the identification of leak sites but also to the improvement and resolution of chylothorax. Therefore, lymphangiography should be considered for refractory chylothorax that is unresponsive to chemotherapy or nutritional management.
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Quilotórax , Linfoma de Células B Grandes Difuso , Derrame Pleural , Aceite Etiodizado , Femenino , Humanos , Linfografía , Persona de Mediana EdadRESUMEN
HLA-haploidentical allogeneic hematopoietic cell transplantation (allo-HCT) using post-transplantation cyclophosphamide (PT/Cy-haplo) is becoming the standard of care for patients without an HLA-matched related or unrelated donor. PT/Cy-haplo can give more patients the opportunity to undergo allo-HCT, because most patients have multiple available HLA-haploidentical related donor candidates. The optimal donor selection algorithm in the PT/Cy-haplo setting has not yet been established, however. To contribute to the establishment of a donor selection formula based on disease status and killer-cell immunoglobulin-like receptor (KIR) genotype, we retrospectively analyzed 91 patients who underwent PT/Cy-haplo at our institution. In both patients and donors, HLA allele genotyping was performed for HLA-A, -B, -C, and -DRB1, and 16 KIR genes were genotyped. Patients in complete remission (CR) who underwent PT/Cy-haplo from a KIR2DS1-positive donor had a significantly lower cumulative incidence of relapse (CIR) than those who underwent PT/Cy-haplo from a KIR2DS1-negative donor (1-year CIR: 0% versus 32.6%, P = .037; 2-year CIR: 9.2% versus 42%, P = .037). Moreover, PT/Cy-haplo from a KIR2DS1-positive donor was significantly associated with improved overall survival (OS) (1-year OS: 91.7% versus 58.7%, P = .010; 2-year OS: 83% versus 34%, P = .010). In contrast, in non-CR individuals, PT/Cy-haplo from KIR2DS1-positive donors did not significantly improve CIR or OS (1-year CIR: 56.5% versus 64.7%, P = .973; 2-year CIR: not reached versus 64.7%, Pnot evaluable; 1-year OS: 25.4% versus 20.6%, P = .418; 2-year OS: 5.1% versus 20.6%, P = .418). In addition, lower infused CD34+ cell dose, female-to-male transplantation, and acute myelogenous leukemia were significantly associated with increased risk of relapse and mortality. This study demonstrates that graft-versus-leukemia/tumor effects were exerted through donor KIR2DS1 at PT/Cy-haplo when patients have low tumor burdens. It would be worth examining the inclusion of donor KIR genotyping and disease status assessment in establishing optimal donor selection criteria for PT/Cy-haplo.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Receptores KIR , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Masculino , Receptores KIR/genética , Recurrencia , Estudios Retrospectivos , Trasplante HaploidénticoRESUMEN
Although elevated serum beta-2 microglobulin (BMG) has been reported as a poor prognostic marker for various hematological malignancies, no study has assessed its prognostic significance in allogenec hematopoietic cell transplantation (allo-HCT). Therefore, we conducted this retrospective observational study in 227 consecutive patients with available pretransplant serum BMG levels between April 2010 and September 2017 at our institute. We also collected and retrospectively analyzed various pretransplant variables likely related to transplant outcomes. Multivariable analysis, including major prognostic variables, such as the disease risk index and the hematopoietic cell transplant-comorbidity index, showed a significant association between higher serum BMG levels and poorer overall survival (OS) in all three adjusted models [hazard ratio (HR) per its standard deviation (SD) (SD = 1.094): 1.67 (1.35-2.03; P < 0.001), HR per SD: 1.46 (1.14-1.86; P = 0.002), HR per SD: 2.03 (1.62-2.55; P < 0.001)], respectively, due to the significant association between higher serum BMG levels and relapse/progression [HR 1.52 (1.20-1.94; P < 0.001)] instead of nonrelapse mortality [HR 1.06 (0.70-1.60; P = 0.780)]. Moreover, DRI and serum BMG had statistically significantly higher c-statistic estimates for OS compared with DRI alone (c-index 0.74 and 0.68, respectively; P < 0.001). In conclusion, pretransplant serum BMG level may serve as a useful prognostic marker and help clinical decision in allo-HCT.
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Trasplante de Células Madre Hematopoyéticas , Humanos , Recurrencia Local de Neoplasia , Pronóstico , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
Refractory viremia/viral disease is a major life-threatening complication that may arise among patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). This study aimed to clarify the therapeutic effect of high-dose polyclonal intravenous immunoglobulin (IVIG) against viremia/viral diseases after allo-HCT. We conducted a pilot study to investigate the therapeutic effect of 400 mg/kg of IVIG given for 5 consecutive days against refractory viremia/viral disease after allo-HCT. Overall, 7 patients were drug-resistant and the other 7 had not previously received any drug for their viremia/viral disease. All patients completed the 5-day therapy regimen of IVIG. A complete response at Day 56 was observed for 8 of 14 patients (57.1%). Additionally, 10 of 14 patients (71.4%) were alive at Day 56, although only one death occurred due to the viremia/viral disease. Remarkably, all 3 cases who developed exogenous viremia/viral diseases including respiratory syncytial virus pneumonia/bronchitis and human parvovirus B19 viremia achieved a complete response, suggesting that high-dose polyclonal IVIG may be more effective against exogenous viruses rather than endogenous ones. Congestive heart failure was observed in 1 patient. High-dose polyclonal IVIG could be an effective and feasible therapy for refractory viremia/viral disease after allo-HCT.
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Trasplante de Células Madre Hematopoyéticas , Viremia/tratamiento farmacológico , Humanos , Inmunoglobulinas Intravenosas , Parvovirus B19 Humano , Proyectos Piloto , Viremia/etiologíaRESUMEN
HLA-haploidentical allogeneic hematopoietic cell transplantation with post-transplantation cyclophosphamide (PT/Cy-haplo) is widely used because of such advantages as low procedure cost, high probability of finding a suitable donor, and donor availability at short notice. Cytokine release syndrome (CRS), resulting from bidirectional alloreaction between host and donor, occurs frequently in recipients of PT/Cy-haplo, especially when peripheral blood is used. Severe and life-threatening instances of CRS have been reported. The clinical significance of CRS remains unclear, however. Here we used serum IL-6 level as a surrogate marker of CRS to evaluate the impact of outcomes in 65 consecutive patients receiving PT/Cy-haplo at our institution. Our results indicate that active disease status, high Hematopoietic Cell Transplantation-Specific Comorbidity Index score, and very severe CRS are significantly related to peak serum IL-6 level. In our cohort, high peak serum IL-6 level and severe CRS were significantly associated with the development of grade III or IV acute graft-versus-host disease (GVHD). High peak serum IL-6 level was identified a significant risk factor for poor 3-year overall survival. Our results suggest that even transient CRS following PT/Cy-haplo may contribute to poor survival owing to an increase in severe acute GVHD.
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Ciclofosfamida/uso terapéutico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Interleucina-6/sangre , Trasplante Haploidéntico/efectos adversos , Adolescente , Adulto , Anciano , Ciclofosfamida/farmacología , Síndrome de Liberación de Citoquinas/etiología , Femenino , Humanos , Inmunosupresores/farmacología , Masculino , Persona de Mediana Edad , Trasplante Haploidéntico/métodos , Adulto JovenRESUMEN
In allogeneic hematopoietic stem cell transplantation (HSCT), ascites may develop owing to several causes, including sinusoidal obstruction syndrome, infections, malignancies, and malnutrition. However, it is often difficult to determine its precise cause. Here, a 59-year-old male developed chylous ascites three months post allogeneic bone marrow transplantation for relapsed acute myeloid leukemia. None of the attempted treatments resulted in improvement. Lymphangioscintigraphy revealed a lymphatic flow disorder at the level of the cisterna chyli. Autopsy revealed no leukemic cell infiltration or graft-versus-host disease of the liver or pancreas. The pancreatic specimen revealed parenchymal fibrosis and infiltration of plasma cells, suggesting chronic inflammation in addition to pathological changes caused by acute pancreatitis. These findings indicate that acute or chronic pancreatitis caused a lymphatic flow disorder that developed into refractory ascites. Although we could not diagnose pancreatitis while the patient was alive, it is important to recognize that asymptomatic pancreatitis can develop after HSCT. Furthermore, one should attempt to make an accurate diagnosis as early as possible.