RESUMEN
Anti-human leukocyte antigen (HLA) antibodies other than those against HLA-A, -B, -C, and DRB1 are a risk factor for engraftment delay and failure, especially in cord blood transplantation (CBT). The primary objective of this study was to assess the impact of the presence of anti-HLA antibodies on CBT and to evaluate the utility of lymphocyte crossmatch testing or additional HLA-DP and -DQ typing of CB units in improving transplant outcomes. We retrospectively assessed the engraftment rates and transplant outcomes of 772 patients who underwent their first CBT at our hospital between 2012 and 2021. Donors were routinely typed for HLA-A, -B, -C, and-DRB1 alleles, and the anti-HLA antibodies of recipients were screened before donor selection in all cases. Among patients who had antibodies against other than HLA-A, -B, -C, and DRB1 (n = 58), lymphocyte crossmatch testing (n = 32) or additional HLA-DP/-DQ alleles typing of CB (n = 15) was performed to avoid the use of units with corresponding alleles. The median patient age was 57 years (16 to 77). Overall, 75.7% had a high-risk disease status at transplantation, 83.5% received myeloablative conditioning regimens, and >80% were heavily transfused. Two hundred twenty-nine of the 772 recipients (29.6%) were positive for anti-HLA antibodies. There were no statistical differences in the number of infused CD34-positive cells between the anti-HLA antibody-positive and the anti-HLA antibody-negative patients. Of the 229 patients with anti-HLA antibodies, 168 (73.3%) had antibodies against HLA-A, -B, -C, and-DRB1 (Group A), whereas 58 (25.3%) had antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5 with or without antibodies against HLA-A, -B, -C, and -DRB1 (Group B). No patients in both Groups A and B exhibited donor-specific anti-HLA antibodies against HLA-A, -B, -C, and -DRB1. The neutrophil engraftment rate was lower in patients with anti-HLA antibodies than in those without antibodies (89.9% versus 94.1%), whereas nonrelapse mortality (NRM) before engraftment was higher in antibody-positive patients (9.6% versus 4.9%). In patients who received 2 or more HLA allele-mismatched CB in the host-versus-graft (HVG) direction (n = 685), the neutrophil engraftment rate was lower in the anti-HLA antibody-positive recipients than in the antibody-negative recipients with significant differences (88.8% versus 93.8%) (P = .049). Similarly, transplant outcomes were worse in the antibody-positive patients with respect to 2-year overall survival (OS) (43.1% versus 52.3%) and NRM (44.0% versus 30.7%) than in the antibody-negative patients. In contrast, the results of Group B were comparable to those of the antibody-negative patients, while those of Group A were statistically worse than the antibody-negative patients in terms of all engraftment rate (88.6%), OS (34.2%), and NRM (49.0%). The presence of anti-HLA antibodies negatively impacts engraftment, NRM, and OS in CBT. However, HLA-DP/-DQ allele typing of CB units or lymphocyte crossmatch testing could be a useful strategy to overcome poor engraftment rates and transplant outcomes, especially in patients with anti-HLA antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5.
Asunto(s)
Alelos , Trasplante de Células Madre de Sangre del Cordón Umbilical , Antígenos HLA-DQ , Prueba de Histocompatibilidad , Humanos , Femenino , Masculino , Adulto , Prueba de Histocompatibilidad/métodos , Persona de Mediana Edad , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/inmunología , Estudios Retrospectivos , Adolescente , Antígenos HLA-DP/genética , Antígenos HLA-DP/inmunología , Adulto Joven , Anciano , Donantes de Tejidos , Linfocitos/inmunología , Isoanticuerpos/sangre , Cadenas HLA-DRB1/genéticaRESUMEN
Tyrosine kinase inhibitors (TKIs) are essential drugs for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Cardiovascular or arteriothrombotic adverse events have been reported in patients treated with TKIs. We report 3 cases of Ponatinib-related vasospastic angina, in which prophylactic administration of nitrates or calcium channel blockers was effective.
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Vasoespasmo Coronario , Leucemia Mielógena Crónica BCR-ABL Positiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Piridazinas , Humanos , Vasoespasmo Coronario/inducido químicamente , Vasoespasmo Coronario/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/inducido químicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/inducido químicamente , Imidazoles/farmacología , Piridazinas/efectos adversosRESUMEN
The number of umbilical cord blood transplantation (U-CBT) procedures has been growing annually, but little research has been done on long-term immune recovery after U-CBT. Infection risk is high in U-CBT recipients, and this can be partially attributed to immature immunocompetent cells in umbilical cord blood. In this study, we analyzed lymphocyte subset (LST) number to determine the long-term recovery timeline. We included 36 U-CBT and 10 unrelated bone marrow transplantation (U-BMT) recipients who survived more than 2 years after transplantation, and followed them for up to 10 years post-transplant. Recovery kinetics in the early phase post-transplant was different for each LST. Recovery of CD19+ B cells was faster after U-CBT than after U-BMT in the first 5 years after transplantation. Although CD4+ T cells increased in the first several months after U-CBT, long-term cell count recovery was impaired in approximately 20% of patients. Thus, although the LST recovery pattern after U-CBT was unique, LST number recovery was statistically comparable between U-CBT and U-BMT past 5 years post-transplantation.
Asunto(s)
Trasplante de Médula Ósea , Trasplante de Células Madre de Sangre del Cordón Umbilical , Subgrupos Linfocitarios , Humanos , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Trasplante de Médula Ósea/métodos , Masculino , Adulto , Femenino , Persona de Mediana Edad , Subgrupos Linfocitarios/inmunología , Adolescente , Reconstitución Inmune , Recuento de Linfocitos , Factores de Tiempo , Niño , Adulto Joven , Preescolar , Estudios de Seguimiento , Linfocitos T CD4-Positivos/inmunología , Donante no EmparentadoRESUMEN
Background/Aim: Acute lymphoblastic leukemia (ALL) is a blood malignancy characterized by a rapid proliferation of lymphoid progenitor cells. Extramedullary relapse (EMR) is the recurrence of leukemia that occurs outside the bone marrow. The central nervous system is the most prevalent site of EMR in ALL, whereas other organs, particularly the renal organs, are less commonly involved. Case Report: A 49-year-old man diagnosed with Philadelphia chromosome-negative ALL (Ph-negative ALL) received a second umbilical cord blood transplant (uCBT) and was confirmed to be in his third hematological complete remission. However, the perirenal mass lesion emerged after two weeks, and was difficult to detect on echography in the prone position. We successfully performed a percutaneous biopsy of the mass in a sitting position and pathologically identified it as EMR. After the diagnosis, chemotherapy was restarted, and the patient was scheduled to receive a third uCBT. Conclusion: This is the first report of EMR in a perirenal lesion of ALL and shows that this novel biopsy can be performed as a renal biopsy, even in a sitting position. This case is the first to describe a biopsy technique in detail and demonstrates the value of collaboration between hematologists and nephrologists in diagnosing EMR of the kidneys.
RESUMEN
Acquired point mutations in the ABL1 gene are widely recognized as a cause of Philadelphia chromosome-positive B cell precursor acute lymphoblastic leukemia (Ph+ B-ALL) that is resistant to tyrosine kinase inhibitors, whereas there are few reports about other types of the ABL1 mutation. Here, we report 2 cases of Ph+ B-ALL gaining a partial deletion type mutation of the ABL1 gene (Δ184-274 mutation), which resulted in truncation of the ABL1 molecule and loss of kinase activity. In both cases, the disease was refractory to multiple agents in the recurrent phase after allogeneic hematopoietic cell transplantation. This is a case report of a truncated ABL1 mutation in 2 patients with Ph+ B-ALL.
Asunto(s)
Proteínas de Fusión bcr-abl , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Proteínas de Fusión bcr-abl/genética , Mutación , Cromosoma Filadelfia , Mutación Puntual , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
INTRODUCTION: This study aimed to identify factors responsible for changes in blood concentrations of a liposomal formulation of amphotericin B (AMPH-B, L-AMB) and analyze the relationships between blood concentrations and efficacy or toxicity. METHODS: L-AMB was administered to 30 patients being treated for hematological diseases. AMPH-B plasma concentrations were determined right before the initiation (Cmin) and at the end (Cmax) of infusion on at least 1 day, beginning on Day 3 of L-AMB treatment. The relationships of Cmin divided by dose (C/D ratio) to body weight, age, hepatic function, renal function, serum albumin, C-reactive protein (CRP), response, hypokalemia, and renal impairment were evaluated. RESULTS: C/D ratio was not correlated with age, hepatic function, renal function, or serum albumin. Body weight adjusted C/D ratio was negatively correlated with CRP. Cmax and Cmin were compared between responders and non-responders, those with or without hypokalemia, and those with or without renal impairment. A higher Cmax in patients with hypokalemia was the only significant difference seen. CONCLUSIONS: The negative correlation between CRP and plasma concentrations was likely caused by higher distribution of L-AMB from the blood to infected tissue in patients with a greater degree of infection, with a resulting decrease in plasma concentrations. AMPH-B plasma concentrations were not related to response. Higher Cmax of AMPH-B were observed in patients with hypokalemia, but no relationship between plasma concentration and renal toxicity was observed, suggesting that AMPH-B plasma concentrations appear to be minimally related to PD when used as L-AMB.
Asunto(s)
Enfermedades Hematológicas , Hipopotasemia , Humanos , Anfotericina B/efectos adversos , Antifúngicos/efectos adversos , Hipopotasemia/inducido químicamente , Hipopotasemia/tratamiento farmacológico , Enfermedades Hematológicas/inducido químicamente , Albúmina Sérica , Proteína C-Reactiva , Peso CorporalRESUMEN
BACKGROUND: Mantle cell lymphoma is considered an aggressive B-cell lymphoma. The optimal induction regimen remains controversial as no randomized controlled trial has compared the efficacy of different induction therapies. METHOD: Herein, we performed a retrospective analysis of the clinical characteristics of 10 patients who received induction treatment consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, bendamustine, and cytarabine (R-BAC) at Toranomon Hospital between November 2016 and February 2022. RESULT: Although one patient discontinued R-BAC therapy due to a rash, the other nine completed the scheduled chemotherapy. All patients achieved complete response, underwent high-dose chemotherapy and autologous stem cell transplantation, and maintained complete remission with a median follow-up of 15 months. Hematological adverse events (AEs) occurred in all patients; however, none developed documented infection. There were also no fatal non-hematological AEs specific to R-BAC. CONCLUSION: R-CHOP/R-BAC may be a good induction therapy for transplant-eligible patients with mantle cell lymphoma.
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Trasplante de Células Madre Hematopoyéticas , Linfoma de Células del Manto , Adulto , Humanos , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/patología , Rituximab/efectos adversos , Estudios Retrospectivos , Clorhidrato de Bendamustina/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante Autólogo , Ciclofosfamida/efectos adversos , Prednisona/efectos adversos , Vincristina/efectos adversos , Citarabina/efectos adversos , Doxorrubicina/efectos adversosRESUMEN
Difficulties in immediately distinguishing Stenotrophomonas maltophilia (SM) bacteremia from Pseudomonas aeruginosa (PA) bacteremia in the clinical setting can lead to treatment delay. We aimed to develop a scoring system to immediately distinguish SM bacteremia from PA bacteremia using clinical indicators. We enrolled cases of SM and PA bacteremia in adult patients with hematological malignancies between January 2011 and June 2018. The patients were randomized into derivation and validation cohorts (2:1), and a clinical prediction tool for SM bacteremia was developed and verified. In total, 88 SM and 85 PA bacteremia cases were identified. In the derivation cohort, the following independent predictors of SM bacteremia were identified: no evidence of PA colonization, antipseudomonal ß-lactam breakthrough bacteremia, and central venous catheter insertion. We scored each of the three predictors according to their regression coefficient (2, 2, and 1, respectively). Receiver operating characteristic curve analysis confirmed the score's predictive performance, with an area under the curve of 0.805. The combined sensitivity and specificity (0.655 and 0.821) was highest with a cut-off value of 4 points. Positive and negative predictive values were 79.2% (19/24) and 69.7% (23/33), respectively. This novel predictive scoring system is potentially useful for distinguishing SM bacteremia from PA bacteremia, which would facilitate immediate administration of appropriate antimicrobial therapy.
Asunto(s)
Bacteriemia , Infecciones por Bacterias Gramnegativas , Neoplasias Hematológicas , Stenotrophomonas maltophilia , Adulto , Humanos , Pseudomonas aeruginosa , Estudios Retrospectivos , Factores de Riesgo , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológicoRESUMEN
Bacterial meningitis is a rare but severe infectious complication after hematopoietic stem cell transplantation. However, its clinical features were previously not clear. We reviewed the cases of 7 patients diagnosed with bacterial meningitis with a positive cerebrospinal fluid culture among 1147 patients who underwent cord blood transplantation (CBT) at our institution between September 2007 and September 2020. The diagnosis was made on day + 5- + 45, and 5 patients developed bacterial meningitis before neutrophil engraftment. The causative organisms were all Gram-positive cocci: Enterococcus faecium and Enterococcus gallinarum (2 patients each), and Staphylococcus haemolyticus, Streptococcus mitis/oralis, and Rothia mucilaginosa (1 patient each). Six patients developed bacterial meningitis secondary to prior or concomitant bacteremia caused by the same bacterium. Five patients had received anti-MRSA agents at onset: vancomycin in 3, teicoplanin in 1, and daptomycin in 1. After diagnosis of bacterial meningitis, linezolid was eventually used for 6 patients. Two patients with E. gallinarum were alive at day + 1380 and + 157 after CBT, respectively, whereas 5 patients died 17-53 (median 43) days after the onset of bacterial meningitis. Breakthrough meningitis in CBT can occur even during the use of anti-MRSA drugs, and intensive antibiotic treatment is necessary.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Daptomicina , Infecciones por Bacterias Grampositivas , Meningitis Bacterianas , Humanos , Antibacterianos/uso terapéutico , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Daptomicina/uso terapéutico , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/etiología , Meningitis Bacterianas/tratamiento farmacológico , Meningitis Bacterianas/etiología , Meningitis Bacterianas/diagnóstico , Pruebas de Sensibilidad Microbiana , Vancomicina/uso terapéuticoRESUMEN
Limited data are available on breakthrough fungemia, defined as fungemia that develops on administration of antifungal agents, in patients with hematological disorders. We reviewed the medical and microbiological records of adult patients with hematological diseases who had breakthrough fungemia between January 2008 and July 2019 at Toranomon Hospital and Toranomon Hospital Kajigaya in Japan. A total of 121 cases of breakthrough fungemia were identified. Of the 121 involved patients, 83, 11, 5, and 22 were receiving micafungin, voriconazole, itraconazole, and liposomal amphotericin B, respectively, when the breakthrough occurred. Of the 121 causative breakthrough fungal strains, 96 were Candida species, and the rest were 13 cases of Trichosporon species, 7 of Fusarium species, 2 of Rhodotorula mucilaginosa, and 1 each of Cryptococcus neoformans, Exophiala dermatitidis, and Magnusiomyces capitatus. The crude 14-day mortality rate of breakthrough fungemia was 36%. Significant independent factors associated with the crude 14-day mortality rate were age of ≥60 years (P = 0.011), chronic renal failure (P = 0.0087), septic shock (P < 0.0001), steroid administration (P = 0.0085), and liposomal amphotericin B breakthrough fungemia (P = 0.0011). An absolute neutrophil count of >500/µL was significantly more common in candidemia in the multivariate analysis (P = 0.0065), neutropenia and nonallogeneic hematopoietic stem cell transplants were significantly more common in Trichosporon fungemia (P = 0.036 and P = 0.033, respectively), and voriconazole breakthrough fungemia and neutropenia were significantly more common in Fusarium fungemia (P = 0.016 and P = 0.016, respectively). The epidemiological and clinical characteristics of breakthrough fungemia of patients with hematological disorders were demonstrated. Some useful factors to predict candidemia, Trichosporon fungemia, and Fusarium fungemia were identified.
Asunto(s)
Candidemia , Cryptococcus neoformans , Fungemia , Fusarium , Enfermedades Hematológicas , Trichosporon , Adulto , Antifúngicos/uso terapéutico , Candida , Candidemia/tratamiento farmacológico , Fungemia/tratamiento farmacológico , Fungemia/microbiología , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/tratamiento farmacológico , Humanos , Persona de Mediana EdadRESUMEN
There are few reports on the clinical course of proven invasive aspergillosis (IA) due to rare/cryptic species in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. We retrospectively reviewed the electronic medical records of patients who underwent allo-HSCT between January 2012 and December 2018. Of 934 allo-HSCT recipients, 10 were diagnosed with proven IA and 61 were diagnosed with probable IA. DNA sequencing was performed in cases of proven IA, and Aspergillus could be identified to the species level in 8 of the 10 cases. Three were due to A. fumigatus, and 5 were due to rare/cryptic Aspergillus species, namely, A. turcosus, A. felis, A. viridinutans, A. nidulans, and A. calidoustus. In these 8 patients, no patients with IA due to A. fumigatus died, whereas 3 of the 5 with IA due to rare/cryptic species died within 12 weeks. The 2 surviving cases of IA due to rare/cryptic species were treated with surgical resection and antifungal treatment. Susceptibility testing for cryptic species in 4 cases showed an amphotericin B MIC > 1 mg/L in 3 cases, itraconazole MIC > 1 mg/L in 2 cases, and voriconazole MIC > 1 mg/L in 2 cases. In conclusion, more than half of the causative pathogens of proven IA were rare/cryptic species, so it is important to accurately identify the Aspergillus species. In addition, surgical treatment might be an important option in cases of proven IA, given the possibility that the causative organisms are azole-resistant A. fumigatus or rare/cryptic species.
Asunto(s)
Aspergilosis , Trasplante de Células Madre Hematopoyéticas , Infecciones Fúngicas Invasoras , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergillus/genética , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs) occur in patients receiving immunosuppressive drugs for autoimmune diseases; however, their clinicopathological and genetic features remain unknown. In the present study, we analysed 67 patients with OIIA-LPDs, including 36 with diffuse large B-cell lymphoma (DLBCL)-type and 19 with Hodgkin lymphoma (HL)-type. After discontinuation of immunosuppressive drugs, regression without relapse was achieved in 22 of 58 patients. Spontaneous regression was associated with Epstein-Barr virus positivity in DLBCL-type (P = 0·013). The 2-year overall survival and progression-free survival (PFS) at a median follow-up of 32·4 months were 92·7% and 72·1% respectively. Furthermore, a significant difference in the 2-year PFS was seen between patients with DLBCL-type and HL-type OIIA-LPDs (81·0% vs. 40·9% respectively, P = 0·021). In targeted sequencing of 47 genes in tumour-derived DNA from 20 DLBCL-type OIIA-LPD samples, histone-lysine N-methyltransferase 2D (KMT2D; eight, 40%) and tumour necrosis factor receptor superfamily member 14 (TNFRSF14; six, 30%) were the most frequently mutated genes. TNF alpha-induced protein 3 (TNFAIP3) mutations were present in four patients (20%) with DLBCL-type OIIA-LPD. Cases with DLBCL-type OIIA-LPD harbouring TNFAIP3 mutations had shorter PFS and required early initiation of first chemotherapy. There were no significant factors for spontaneous regression or response rates according to the presence of mutations. Overall, OIIA-LPDs, especially DLBCL-types, showed favourable prognoses.
Asunto(s)
Síndromes de Inmunodeficiencia/inducido químicamente , Inmunosupresores/efectos adversos , Linfoma/inducido químicamente , Enfermedades Reumáticas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Herpesvirus Humano 4/aislamiento & purificación , N-Metiltransferasa de Histona-Lisina/genética , Enfermedad de Hodgkin/inducido químicamente , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/inmunología , Humanos , Enfermedad Iatrogénica , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Estimación de Kaplan-Meier , Linfoma/tratamiento farmacológico , Linfoma/genética , Linfoma/inmunología , Linfoma de Células B Grandes Difuso/inducido químicamente , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/inmunología , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Metotrexato/uso terapéutico , Persona de Mediana Edad , Proteína de la Leucemia Mieloide-Linfoide/genética , Pronóstico , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Miembro 14 de Receptores del Factor de Necrosis Tumoral/genética , Estudios Retrospectivos , Tacrolimus/administración & dosificación , Tacrolimus/efectos adversos , Tacrolimus/uso terapéutico , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genéticaAsunto(s)
Trasplante de Médula Ósea/efectos adversos , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Reconstitución Inmune/inmunología , Linfocitos/citología , Trasplante de Médula Ósea/métodos , Trasplante de Médula Ósea/estadística & datos numéricos , Estudios de Casos y Controles , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Trasplante de Células Madre de Sangre del Cordón Umbilical/estadística & datos numéricos , Citometría de Flujo/métodos , Enfermedad Injerto contra Huésped/epidemiología , Humanos , Incidencia , Cinética , Recuento de Linfocitos/estadística & datos numéricos , Recuento de Linfocitos/tendencias , Linfocitos/inmunología , Pronóstico , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Donante no EmparentadoRESUMEN
Limited data are available on Stenotrophomonas maltophilia bloodstream infections (SM-BSIs) and the therapeutic efficacy of trimethoprim-sulfamethoxazole (SXT) against SM-BSI in umbilical cord blood transplant (uCBT) recipients. Medical and microbiological records of adult patients who received uCBTs between December 2008 and December 2015 at Toranomon Hospital (Tokyo, Japan) were reviewed. The efficacy and safety of SXT were evaluated only for recipients who were treated with ≥7 days of intravenous SXT for SM-BSI (evaluation cohort). Of 561 uCBT recipients, 34 developed SM-BSI. Diabetes mellitus (P = .005) and age ≥ 60 years (P = .013) were significant independent risk factors for SM-BSI. Moreover, SM-BSI was identified as an independent risk factor for all-cause mortality up to 100 days following uCBT (P = .025). Of the 34 recipients with SM-BSI, 24 were treated with an intravenous SXT-containing regimen (iSXT-CR). Septic shock (P = .0021), pneumonia (P = .011), neutropenia (P = .0015), and systemic steroid administration (P = .018) were identified as significant independent risk factors for 7-day crude mortality. The evaluation cohort included nine recipients. Doses of SXT were 2.4 to 6.9 mg/kg/day of the trimethoprim component. Of the nine recipients, five developed SM-BSI during the pre-engraftment phase. The 30-day crude-mortality rate and clinical cure rate of the cohort were 22% and 67%, respectively. Only one of the nine recipients experienced significant neutrophil toxicity. In this study, the epidemiology of SM-BSI in uCBT recipients was determined and its negative impact on survival was demonstrated. A low- to moderate-dose iSXT-CR appeared to be a tolerable and important therapeutic option for SM-BSI in the uCBT setting, including during the pre-engraftment phase.
Asunto(s)
Bacteriemia , Trasplante de Células Madre de Sangre del Cordón Umbilical , Infecciones por Bacterias Gramnegativas , Stenotrophomonas maltophilia , Adulto , Bacteriemia/tratamiento farmacológico , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Japón , Persona de Mediana Edad , Estudios Retrospectivos , TokioRESUMEN
Bloodstream infection (BSI) is a major infectious complication after allogeneic hematopoietic cell transplantation (HCT). To clarify the impact of graft cell source on the incidence of BSI after transplantation, we retrospectively examined 782 adult patients receiving their first allogeneic HCT: 122 recipients of related peripheral blood stem cells or bone marrow, 215 recipients of unrelated bone marrow, and 445 recipients of unrelated umbilical cord blood (U-CB). The cumulative incidence of BSI was 42.5% at 100 days after transplantation (95% confidence interval, 39.0-46.0). Gram-positive cocci were present in 64.2% of detected isolates. Among the pre-transplant factors including age, performance status, primary disease, disease status, graft cell source, sex and ABO blood type matching, and the intensity of conditioning regimen, U-CB use was identified as the most significant risk factor for BSI by multivariate analysis (hazard ratio, 1.76; 95% confidence interval, 1.40-2.22; p < 0.00001). Among the U-CB recipients, those who are not in remission at the time of transplantation were at the greatest risk of BSI (hazard ratio, 1.69; 95% confidence interval, 1.14-2.50; p < 0.01). The study makes it clear that graft cell source has an impact on BSI development after allogeneic HCT.
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Bacteriemia , Enfermedades Transmisibles , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversosRESUMEN
The aim of this study is to clarify the characteristics of gram-negative bacteremia (GNB), including extended-spectrum ß-lactamase (ESBL)-producing pathogens, among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients on levofloxacin (LVFX) prophylaxis. A retrospective analysis on GNB at the first episode of febrile neutropenia (FN) was conducted among allo-HSCT recipients (age ≥ 20 years) on 500 mg/day of oral LVFX prophylaxis. Epidemiological and microbiological features of GNB were investigated and compared between the inappropriate and appropriate empiric therapy groups. In total, FN occurred in 414 allo-HSCT cases, and bacteremia at the first episode of FN occurred in 169 cases. Overall, 29 GNB cases were documented, and the causative organisms identified were Escherichia coli in 21 cases (including 10 ESBLs), Klebsiella pneumoniae in 2, Pseudomonas aeruginosa in 2, and other in 4. The crude 30-day mortality rate was not significantly different among cases of GNB (6.9%), gram-positive bacteremia (GPB) (7.1%), or non-bacteremia (5.4%; P = 0.78). Cefepime (CFPM) was administered in all cases in the inappropriate empiric therapy group, and all causative organisms were ESBL-producing E. coli (ESBL-EC). All patients in the inappropriate empiric therapy group had a low Pitt bacteremia score (≤ 2). Thirty-day mortality did not differ significantly between the inappropriate and appropriate empiric therapy groups (1/10 vs. 1/15, P = 0.61). In conclusion, GNB was not a significant cause of death. In LVFX breakthrough ESBL-EC bacteremia among allo-HSCT recipients, the administration of CFPM as empiric therapy did not lead to significantly poor prognosis. Empiric CFPM administration might be an acceptable strategy.
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Antibacterianos/uso terapéutico , Bacteriemia/microbiología , Infecciones por Bacterias Gramnegativas/microbiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Levofloxacino/uso terapéutico , Neutropenia/microbiología , Adulto , Anciano , Femenino , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Receptores de Trasplantes , Adulto JovenRESUMEN
Recent progress in genetic analysis technology has helped researchers understand the pathogenesis of acute myeloid leukemia (AML). Considering this progress, AML karyotype is still one of the most significant prognostic factors that provides risk-adapted treatment approaches. Karyotype changes during treatment have been observed at times, but their prognostic impact is sparse, especially on allogeneic stem cell transplantation (allo-SCT). Here, we retrospectively investigated the effect of chromosomal changes between diagnosis and pretransplantation on the prognosis of allo-SCT by analyzing the outcomes of 212 consecutive patients who underwent allo-SCT for the first time at Toranomon Hospital, Tokyo, Japan, between 2008 and 2018. Cytogenetic abnormalities at diagnosis and pretransplantation were categorized based on the 2017 European Leukemia Net risk stratification. Genetic abnormalities such as FLT3-ITD and NPM1 were not considered in this study due to lack of genetic information in most patients. We defined cytogenetic evolution as chromosomal changes classified from lower category to higher category. Seventeen patients (8%) had cytogenetic evolution between diagnosis and pretransplantation, and they showed a significantly worse relapse rate than those who were categorized in the intermediate group based on the karyotype at diagnosis (3-year confidence interval [CI] of relapse, 57.4% versus 24.9%; P < .01). In multivariate analysis, cytogenetic evolution before allo-SCT had a significant impact on the CI of relapse (hazard ratio [HR], 3.89; CI, 1.75 to 8.67; P < .01), as well as the high score of the hematopoietic cell transplantation-specific comorbidity index (HR, 0.54; CI, 0.31 to 0.94; P = .03), but had no significant impact on overall survival or nonrelapse mortality. These results indicate that cytogenetic evolution has a significant impact after allo-SCT and should be considered during AML treatment.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Análisis Citogenético , Humanos , Japón , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Nucleofosmina , Pronóstico , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
Delayed neutrophil engraftment (NE) has been reported in cord blood transplantation (CBT) compared with other stem cell transplantation methods. The numbers of total nucleated cells (TNCs), CD34+ cells (generally ≥ 1â¯×â¯105/kg), and granulocyte/macrophage colony-forming units (CFU-GM) significantly impact NE. Splenomegaly exerts negative effects on NE, but the appropriate cell dose for the patients with splenomegaly has not yet been determined, especially in CBT. We retrospectively investigated the effect of splenomegaly and number of CD34+ cells infused on NE through the analysis of outcomes of 502 consecutive patients who underwent single CBT for the first time at Toranomon Hospital between 2011 and 2018. Spleen index, Lmaxâ¯×â¯Hvert (SI Lmaxâ¯×â¯Hvert), was defined as maximal length at any transverse section, (Lmax)â¯×â¯vertical height (Hvert), and splenomegaly was defined as SI Lmaxâ¯×â¯Hvert ≥ 115 cm2. Our results show that splenomegaly (hazard ratio [HR], .60; P < .01) and low dose of infused CD34+ cells (HR, .58; P < .01) had significant negative impact on NE, whereas neither CFU-GM dose nor TNC dose had any impact on NE in multivariate analysis. Other factors with a significant negative impact on NE in multivariate analysis were myeloid disease (HR, .62; P < .01), nonremission status at CBT (HR, .71; P < .01), low Eastern Cooperative Oncology Group Performance Status (HR, .68; P < .01), and graft-versus-host disease prophylaxis (other than tacrolimus alone) (HR, .76; P < .01). Without splenomegaly, even patients infused with < .8â¯×â¯105/kg CD34+ cells achieved up to 94.3% NE, with the median value observed at 21 days post-CBT. This study shows that splenomegaly has a significant negative impact on NE after CBT. Cord blood units with < .8â¯×â¯105/kg CD34+ cells may still be a suitable choice for patients without splenomegaly.