RESUMO
BACKGROUND: Conventional conditioning regimens for children with lymphoid malignancy undergoing allogeneic hematopoietic cell transplantation (HCT) are myeloablative and involve high-dose total body irradiation (TBI). Such regimens are associated with significant late complications. OBSERVATIONS: Here, we used a reduced-toxicity conditioning regimen comprising fludarabine, cytarabine, melphalan, and low-dose TBI (FLAMEL) to treat 5 patients with lymphoid malignancy before HCT. Four patients maintained complete remission (range, 18 to 63 mo), whereas the remaining patient who had positive minimal residual disease (MRD) before HCT relapsed. CONCLUSIONS: FLAMEL might be a suitable conditioning regimen for children with lymphoid malignancy if pre-HCT MRD is negative.
RESUMO
The dosage of chemotherapy drugs for overweight/obese children with acute myeloid leukemia (AML) has been empirically reduced based on ideal body weight (BW) in Japan to reduce the risk of adverse events. We investigated the associations between pre-therapeutic body mass index (BMI) and clinical outcomes among children with AML. A total of 280 children were divided into two groups based on the World Health Organization Child Growth Standards: a healthy-weight group (n = 254), and an overweight/obese group (n = 26). If BW exceeded 1.2 times the standard BW of Japanese children, the dosage of chemotherapy drugs was calculated using 1.2 times the standard BW. The dosage of chemotherapy drugs was reduced during at least one chemotherapy cycle in 24 of 26 patients (92.3%) in the overweight/obese group, compared with zero patients in the healthy-weight group. Overall/event-free survival, cumulative incidence of relapse, and treatment-related mortality (TRM) did not differ between the overweight/obese and healthy weight groups. However, the frequency of bacteremia was higher in the overweight/obese group (80.8 vs. 52.4%, P = 0.006). This indicates that TRM may increase when chemotherapy drug dosage is not corrected in overweight/obese patients. Drug reduction is a potential treatment strategy.
Assuntos
Índice de Massa Corporal , Leucemia Mieloide Aguda , Sobrepeso , Humanos , Criança , Masculino , Feminino , Leucemia Mieloide Aguda/tratamento farmacológico , Japão/epidemiologia , Pré-Escolar , Adolescente , Sobrepeso/complicações , Obesidade/complicações , Lactente , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , População do Leste AsiáticoRESUMO
BACKGROUND: Recent studies about inter-reporter differences and patient-reported outcomes (PROs) in childhood cancer from Western countries showed that caregiver proxy reports tend to overestimate symptom burdens in comparison with children's self-reports. However, the results from Western countries may not be generalizable to Asian countries. METHODS: This paper is a secondary analysis of a validation study of the Japanese pediatric version of the Memorial Symptom Assessment Scale including 88 dyads of children aged 7-12 years and 74 dyads of children aged 13-18 years and their caregivers. The study assessed the inter-reporter differences of eight and 31 symptom burdens calculated as symptom scores in children aged 7-12 years and 13-18 years, respectively, and the association between inter-reporter differences and the characteristics of children and caregivers. RESULTS: The majority of children and caregivers scored equally at the dyadic level for almost all symptoms. However, 37.5% of symptoms in children aged 7-12 years and 10.0% of symptoms in children aged 13-18 years showed significant inter-reporter differences, suggesting a general tendency of caregivers to underestimate their children's symptom burden. The caregiver's age was the characteristic most frequently associated with magnitude of inter-reporter differences. CONCLUSIONS: Caregiver proxy reports may be a reliable source of PROs in Japanese children with cancer, as self-reported and caregiver proxy-reported symptom burdens were generally concordant. However, as some significant inter-reporter differences were observed, an effort should be made within the medical community to evaluate the parent-child relationship to minimize inter-reporter differences and achieve better symptom management.
Assuntos
Neoplasias , Carga de Sintomas , Humanos , Criança , Japão , Cuidados Paliativos , Autorrelato , CuidadoresRESUMO
ETV6::Fyn-related kinase (FRK), which is a Src family tyrosine-kinase-related fusion gene and firstly identified in our patient with paediatric high risk B cell precursor acute lymphoblastic leukaemia (B-ALL), has no evidence of efficacy of tyrosine kinase inhibitor in vivo. We performed functional analysis of ETV6::FRK to establish molecular targeting therapy and determined that dasatinib could abrogate proliferation activity of ETV6::FRK through the repression of FRK-STAT3/STAT5 pathway in vitro and significantly extended the survival time of the xenografted mice in vivo (p < 0.01). Our data support the potential of dasatinib as a therapeutic option for patients with B-ALL harboring FRK rearrangements.
RESUMO
BACKGROUND: Preventing infection and managing febrile neutropenia (FN) is mandatory for children with cancer undergoing chemotherapy. However, the current situation in Japan is unknown. METHODS: We conducted a nationwide web-based questionnaire survey in 153 institutions treating childhood cancer in Japan. We asked about the type prophylaxis used to prevent infectious disease and manage FN. If patients with childhood cancer were managed by both pediatricians and surgeons at the same institution, we asked both to reply. RESULTS: We received replies from 117 departments at 111 centers: of these, 108 were from pediatricians. Laminar air flow for neutropenic patients, and frequent hand sanitization with ethanol, were widespread. Twenty-eight percent and forty percent of departments performed active surveillance by taking cultures from patients and the environment, respectively, before initiation of chemotherapy. Forty-four percent of departments administered prophylactic intravenous antibiotics according to patient status. Many departments measured serum (1,3)-ß-D glucan, procalcitonin, and aspergillus galactomannan at the onset of FN. Twenty-eight percent of departments used carbapenem as empirical therapy for FN. Some departments used prophylactic granulocyte-colony stimulating factor for acute leukemia. Seventy-two percent of departments used prophylactic immunoglobulin for hypogammaglobinemia caused by chemotherapy. Palivizumab was administered widely for respiratory syncytial virus prophylaxis in immunocompromised infants. CONCLUSION: As a whole, intensive care for infectious prophylaxis or FN is applied in Japan; however, the methods vary among centers, and some are excessive or inadequate. Therefore, it is desirable to conduct clinical trials and establish adequate care protocols for infection in children with cancer in Japan.
Assuntos
Antineoplásicos , Neutropenia Febril , Controle de Infecções , Infecções , Neoplasias , Criança , Humanos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças Transmissíveis/complicações , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/etiologia , Neutropenia Febril/prevenção & controle , Febre/induzido quimicamente , Febre/etiologia , Febre/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Controle de Infecções/métodos , Infecções/etiologia , Internet , Japão , Leucemia Mieloide Aguda/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Inquéritos e QuestionáriosRESUMO
PURPOSE: Artemis is an exonuclease essential for V(D)J recombination and repair of DNA double-stranded breaks. Pathogenic variants in DCLRE1C encoding Artemis cause T-B-NK+ severe combined immunodeficiency (SCID), and patients with Artemis-deficient SCID (ART-SCID) require definitive therapy with allogeneic hematopoietic cell transplantation (HCT). Here we describe the clinical and genetic characteristics of patients with ART-SCID who were diagnosed in Japan from 2003 to 2022. METHODS: Clinical data of ART-SCID patients who were diagnosed between 2003 and 2022 in Japan were collected from their physicians using a questionnaire. RESULTS: ART-SCID diagnosis was made in eight patients from seven families with severe infections within 6 months of life. Two patients had missense variants, five patients had large genomic deletions, and one patient was compound heterozygous for a missense variant and large genomic deletion. All eight underwent allogeneic HCT within 4 months after the diagnosis, 7 receiving a conditioning regimen containing alkylating agents, and one patient without conditioning due to uncontrolled infection. Two patients with poor performance status (PS) died of complications 410 days and 32 days post-HCT, respectively. Of the six surviving patients with a median follow-up time of 8.3 (0.5-17.9) years, three patients had growth retardation. The patients with PS of 0-2 showed a tendency for better overall survival than those with PS 3-4. CONCLUSION: Large deletions were the most common genetic cause of ART-SCID in Japan. To improve HCT outcome, early diagnosis with newborn screening for SCID is urgently needed.
Assuntos
Proteínas de Ligação a DNA , Imunodeficiência Combinada Severa , Recém-Nascido , Humanos , Proteínas de Ligação a DNA/genética , Mutação , Japão , Proteínas Nucleares/genética , Linfócitos B/patologia , Imunodeficiência Combinada Severa/genética , EndonucleasesRESUMO
CD19-specific chimeric antigen receptor T (CAR T) immunotherapy is used to treat B-cell malignancies. However, antigen-escape mediated relapse following CAR T therapy has emerged as a major concern. In some relapsed cases, especially KMT2A rearrangement-positive B-acute lymphoblastic leukemia (KMT2A-r B-ALL), most of the B-cell antigens are lost via lineage conversion to the myeloid phenotype, rendering multi-B-cell-antigen-targeted CAR T cell therapy ineffective. Fms-related tyrosine kinase-3 (FLT3) is highly expressed in KMT2A-r B-ALL; therefore, in this study, we aimed to evaluate the antitumor efficacy of CAR T cells targeting both CD19 and FLT3 in KMT2A-r B-ALL cells. We developed piggyBac transposon-mediated CAR T cells targeting CD19, FLT3, or both (dual) and generated CD19-negative KMT2A-r B-ALL models through CRISPR-induced CD19 gene-knockout (KO). FLT3 CAR T cells showed antitumor efficacy against CD19-KO KMT2A-r B-ALL cells both in vitro and in vivo; dual-targeted CAR T cells showed cytotoxicity against wild-type (WT) and CD19-KO KMT2A-r B-ALL cells, whereas CD19 CAR T cells demonstrated cytotoxicity only against WT KMT2A-r B-ALL cells in vitro. Therefore, targeting FLT3-specific CAR T cells would be a promising strategy for KMT2A-r B-ALL cells even with CD19-negative relapsed cases.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Humanos , Antígenos CD19/genética , Tirosina Quinase 3 Semelhante a fms/genética , Imunoterapia , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos Quiméricos/genética , Linfócitos T , Proteína de Leucina Linfoide-Mieloide/metabolismo , Histona-Lisina N-Metiltransferase/metabolismoRESUMO
Erythroid sarcoma is a very rare subtype of myeloid sarcoma with undetermined biological features. Here, we present an infant with a multifocal erythroid sarcoma, diagnosed because the tumor cells were positive for glycophorin A. After acute myeloid leukemia-oriented chemotherapy and surgical resection followed by cord blood transplantation, he has successfully maintained complete remission without any late effects. Total transcriptome analysis of the tumor identified a novel fusion gene, RCC1-LCK, and high LCK expression levels, suggesting that LCK overexpression was involved in leukemogenesis in this case.
Assuntos
Leucemia Mieloide Aguda , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Sarcoma Mieloide , Sarcoma , Proteínas de Ciclo Celular , Fatores de Troca do Nucleotídeo Guanina , Humanos , Lactente , Leucemia Mieloide Aguda/genética , Masculino , Proteínas Nucleares , Sarcoma Mieloide/genéticaRESUMO
Post-transplant cyclophosphamide (PTCy) has improved the efficacy of HLA-mismatched hematopoietic cell transplantation (HCT) by decreasing the risk of graft-versus-host disease (GVHD) and nonrelapse mortality. If an HLA-matched donor is not available, GVHD prophylaxis with PTCy can also be used for HLA-mismatched HCT in patients with pediatric aplastic anemia (AA). We report two cases of pediatric AA that were treated with HLA-mismatched HCT with reduced-intensity conditioning and PTCy. We administered 50 mg/kg/day Cy for GVHD prophylaxis on days 3 and 4, and tacrolimus and mycophenolate mofetil (or methotrexate) were initiated from day 5. In both the cases, the time to engraftment was favorable and GVHD and infection were controllable. PTCy probably allows us to expand donor candidates in pediatric AA when an HLA-matched donor is not available; however, further studies regarding optimal conditioning regimens and late complications are required.
Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Transplante de Medula Óssea , Criança , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Condicionamento Pré-TransplanteRESUMO
CONTEXT: Few instruments in Japanese assess health-related quality of life in pediatric cancer patients. OBJECTIVES: To translate the Memorial Symptom Assessment Scale (MSAS) into Japanese pediatric and proxy versions (MSAS-J 7-12, MSAS-J 13-18, and MSAS-J-Proxy) and assess validity and reliability. METHODS: Phase I comprised forward-backward translation and pilot testing in 13 children and 16 guardians. Phase II consisted of psychometric testing of the three MSAS-J versions in 162 children and 238 guardians. Internal consistency, test-retest reliability, and construct and known-group validity of the MSAS-J were assessed. RESULTS: Cronbach's alpha coefficients for the total and subscale scores were over 0.70, excluding the psychological symptom (PSYCH) subscale score of the MSAS-J 7-12. Most MSAS-J scores significantly inversely correlated with two versions of the Pediatric Quality of Life Inventory. A strong child-guardian correlation was shown in the total and subscale scores (ICC range 0.66-0.83). Kappa estimates showed acceptable child-guardian symptom agreement. MSAS-J 7-12 and proxy differentiated patients according to clinical status. CONCLUSION: MSAS-J is a reliable and valid instrument to assess symptoms among Japanese children with cancer.
Assuntos
Neoplasias , Qualidade de Vida , Criança , Humanos , Japão , Neoplasias/diagnóstico , Neoplasias/psicologia , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Avaliação de SintomasRESUMO
Fanconi anemia (FA) is a rare genetic disorder that manifests as congenital abnormalities and bone marrow failure (BMF). Most patients with FA present with BMF within the first decade of life; however, neonate and early infancy BMF is rare. Recent studies have shown that a defective aldehyde dehydrogenase 2 (ALDH2) variant accelerates BMF development in patients with FA. Herein, we described an infant case of FA with compound heterozygous FANCI mutation and the defective ALDH2 variant. Our case developed BMF early probably because of ALDH2 deficiency, while the mild malformation might be because of the locus of FANCI mutation.
Assuntos
Anemia de Fanconi , Aldeído-Desidrogenase Mitocondrial/genética , Anemia de Fanconi/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética , Humanos , Lactente , Recém-Nascido , MutaçãoAssuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Grânulos Citoplasmáticos/patologia , Leucemia Mieloide Aguda/genética , Proteínas de Fusão Oncogênica/genética , Proteína 1 Parceira de Translocação de RUNX1/genética , Síndrome de Chediak-Higashi/diagnóstico , Criança , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patologia , Masculino , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologiaRESUMO
BACKGROUND: L-asparaginase (L-Asp)-associated thromboembolisms are serious complications in pediatrics patients with acute lymphoblastic leukemia (ALL), especially at ≥10.0 years old, but the pathogenesis remains to be clarified. PROCEDURE: We conducted a multicenter, prospective study of 72 patients with ALL aged 1.0 to 15.2 years treated with either a Berlin-Frankfurt-Münster (BFM) 95-ALL oriented regimen or Japan Association of Childhood Leukemia Study ALL-02 protocol. We divided patients into each treatment protocol and investigated the dynamic changes in coagulation and fibrinolysis using simultaneous thrombin and plasmin generation assay. Patients' plasma samples were collected at the prephase (T0), intermittent phase (T1), and postphase of L-Asp therapy (T2), and postinduction phase (T3). Measurements of endogenous thrombin potential (T-EP) and plasmin peak height (P-Peak) were compared to normal plasma. RESULTS: None of the cases developed thromboembolisms. Median ratios of T-EP and P-Peak for the controls in the JACLS group were 1.06 and 0.87 (T0), 1.04 and 0.71 (T1), 1.02 and 0.69 (T2), and 1.20 and 0.92 (T3), respectively, while those in the BFM group were 1.06 and 1.00 (T0), 1.04 and 0.64 (T1), 1.16 and 0.58 (T2), and 1.16 and 0.85 (T3), respectively. In particular, P-Peak ratios were depressed at T1 and T2 compared to T0 in the BFM group (P < .01). Moreover, P-Peak ratios in patients ≥10.0 years old were lower at T1 in the BFM group (P = .02). CONCLUSIONS: The results demonstrated that hemostatic dynamics appeared to shift to a hypercoagulable state with marked hypofibrinolysis associated with L-Asp therapy, especially in patients ≥10.0 years old following the BFM regimen.
Assuntos
Asparaginase/efeitos adversos , Transtornos da Coagulação Sanguínea/patologia , Fibrinolisina/metabolismo , Fibrinólise/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Trombina/metabolismo , Adolescente , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Asparaginase/administração & dosagem , Transtornos da Coagulação Sanguínea/induzido quimicamente , Transtornos da Coagulação Sanguínea/metabolismo , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Quimioterapia de Indução , Lactente , Japão , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Estudos ProspectivosRESUMO
Optimal supportive care for disseminated intravascular coagulation (DIC) and hemostatic complications by asparaginase is indispensable for the successful treatment of pediatric leukemia. However, the situation regarding this type of care in Japan is unclear. We conducted a questionnaire-based survey at 155 institutions treating childhood leukemia in Japan. The questionnaire asked about the supportive care provided by each institution to acute leukemia patients with DIC and asparaginase-induced hemostatic alterations. Ninety-eight institutions responded. The most common diagnostic criteria for DIC were those established by the Japanese Ministry of Health and Welfare. Regardless of the etiology underlying DIC, recombinant human thrombomodulin and synthetic protease inhibitors were used as anticoagulation therapy by around 70% and 40% of institutions, respectively. Additionally, 92%, 93%, and 73% of institutions measured plasma antithrombin, fibrinogen, and D-dimer/fibrin degradation products, respectively, more than twice per week during induction therapy for acute lymphoblastic leukemia. Survey responses indicate that 95% and 24% of the institutions used antithrombin replacement and fresh-frozen plasma, respectively. Supportive care for DIC and/or asparaginase-induced hemostatic alterations at Japanese pediatric centers was intensive and differs markedly from protocols in other countries. The efficacy of supportive care should be evaluated prospectively in the setting of pediatric leukemia.
Assuntos
Hemostáticos/efeitos adversos , Leucemia/complicações , Cuidados Paliativos/métodos , Anticoagulantes , Asparaginase/efeitos adversos , Criança , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/terapia , Humanos , Japão , Leucemia/tratamento farmacológico , Pediatria , Inibidores de Proteases/uso terapêutico , Inquéritos e Questionários , Trombomodulina/uso terapêuticoRESUMO
Gastrointestinal (GI) tract involvement in Langerhans cell histiocytosis (LCH) is extremely rare. Langerhans cell histiocytosis with GI tract involvement (GI-LCH) is frequently associated with multi-system disease, and usually presents with severe systemic symptoms, such as protein-losing enteropathy (PLE). Although the GI tract is not included among the organs at risk, the prognosis of GI-LCH is poor, and no effective chemotherapeutic regimen has been identified. Here, we report an infant case of primary refractory GI-LCH with PLE that showed marked improvement in response to 2-chlorodeoxyadenosine (2-CdA) therapy with no severe adverse events, even under conditions of deteriorating general health. The present findings indicate that 2-CdA may be effective for refractory GI-LCH with PLE. Further studies are warranted to determine the optimal therapeutic strategies for GI-LCH with PLE.
Assuntos
Cladribina/uso terapêutico , Trato Gastrointestinal/patologia , Histiocitose de Células de Langerhans/tratamento farmacológico , Terapia de Salvação/métodos , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/patologia , Humanos , Lactente , Pediatria , Enteropatias Perdedoras de Proteínas/tratamento farmacológico , Enteropatias Perdedoras de Proteínas/etiologia , Resultado do TratamentoRESUMO
A 19-year-old male with therapy-related myelodysplastic syndrome underwent allogeneic bone marrow transplantation with reduced-intensity conditioning from his HLA-identical sibling whose ABO blood type exhibited major incompatibility with the patient. After post-transplantation 1 month, chimerism analysis of the bone marrow revealed mixed chimerism with 30% of recipient cells, and after post-transplantation 3 months, complete remission was maintained; however, recipient granulocytes were elevated up to 50% per the chimerism analysis. Next, pancytopenia developed following the rapid discontinuation of the immunosuppressive agent. Although neutrophils and platelets spontaneously recovered, anemia progressed. Based on severe erythroid hypoplasia in the bone marrow and the elevation of anti-ABO isohemagglutinin against donor-derived red blood cells, the patient was diagnosed with pure red cell aplasia (PRCA) following hematopoietic cell transplantation. Because complete chimerism was attained at the PRCA onset even for B cells, we decided to conservatively manage PRCA with only red blood cell transfusion. Notably, after 2 months of the PRCA onset, anemia improved. This case suggests that the therapeutic strategy for PRCA following hematopoietic cell transplantation should be determined by considering the status of each patient, including chimerism.
Assuntos
Transplante de Medula Óssea , Aplasia Pura de Série Vermelha , Sistema ABO de Grupos Sanguíneos , Adulto , Incompatibilidade de Grupos Sanguíneos , Quimerismo , Ciclosporina , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Aplasia Pura de Série Vermelha/terapia , Transplante Homólogo , Adulto JovemRESUMO
Mixed lineage leukemia [MLL; now known as lysine methyltransferase 2A (KMT2A)] rearrangement-positive acute myeloid leukemia (AML) and juvenile myelomonocytic leukemia (JMML) are distinct diseases, although age of susceptibility (infancy or early childhood) and abnormal monocytosis are common clinical features. Here, we report two cases of KMT2A-rearranged infantile AML masquerading as JMML at initial presentation. Both cases showed leukocytosis accompanied by atypical monocytosis. However, in both cases, leukemic blasts were absent at the initial examination. Thus, a diagnosis of JMML was suspected. However, initial cytogenetic analysis revealed that both cases had an 11q23 rearrangement, which is atypical in JMML. Eventually, due to the emergence of leukemic blasts and further cytogenetic studies, both cases were diagnosed with infantile AML with a KMT2A rearrangement. Although one patient remains in complete remission after the completion of AML appropriate chemotherapy, the other died of AML due to treatment failure. Our experience suggests that AML with KMT2A rearrangement should be considered for the differential diagnosis of infantile cases with atypical monocytosis suggestive of JMML. Cytogenetic studies, including fluorescence in situ hybridization analysis of KMT2A, may be helpful in distinguishing between AML with KMT2A rearrangement and JMML.
Assuntos
Rearranjo Gênico , Predisposição Genética para Doença , Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mielomonocítica Juvenil/diagnóstico , Leucemia Mielomonocítica Juvenil/genética , Proteína de Leucina Linfoide-Mieloide/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Análise Mutacional de DNA , Diagnóstico Diferencial , Estudos de Associação Genética , Humanos , Lactente , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mielomonocítica Juvenil/tratamento farmacológico , Contagem de Leucócitos , Masculino , FenótipoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Região Lombossacral , Polirradiculopatia/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Pré-Escolar , Feminino , Gadolínio , Humanos , Quimioterapia de Indução , Injeções Espinhais , Imageamento por Ressonância Magnética , Polirradiculopatia/diagnóstico por imagemRESUMO
HLA-Flow is a flow cytometry-based method using anti-HLA antibodies against mismatched HLA alleles combined with the antibodies against antigens expressed on leukemic cells. It is a sensitive assay to determine minimal residual disease (MRD) after HLA mismatched hematopoietic stem cell transplantation (HSCT). In this study, we report the results of our HLA-Flow using six-color based multicolor fluorescence-activated cell sorting for HLA-mismatched HSCT. We performed HLA-Flow monitoring after HLA mismatched HSCT from July 2013 to July 2016 in nine patients (three with acute lymphoblastic leukemia, five with acute myeloid leukemia, and one with therapy-related acute myeloid leukemia) for MRD monitoring. We detected a relapse after HSCT in three of the nine patients, two of them at MRD levels. HLA-Flow is a sensitive, fast, and inexpensive method for the detection of MRD in patients with HLA-mismatched HSCT.