RESUMEN
Thrombosis in myeloproliferative neoplasms (MPNs) is an important clinical problem, and risk-stratified management is essential. To identify the clinical characteristics of thrombosis in patients with MPNs, a nationwide multi-institutional retrospective analysis (JSH-MPN-R18) was conducted. The aim of the present study was to perform a sub-analysis of JSH-MPN-R18 findings to clarify the predictive parameters for thrombosis among complete blood count (CBC) results. Among the patients enrolled in JSH-MPN-R18, those with essential thrombocythemia (ET; n = 1152) and polycythemia vera (PV; n = 456) were investigated. We analyzed and compared CBC parameters between patients with and those without any thrombotic events using Welch's T-test. Statistical analyses were performed using the R statistical software. Thrombotic events were observed in 74 patients with ET. In multivariate analysis, only the neutrophil ratio was slightly but significantly higher for ET patients with thrombosis than for those without (p < 0.05). Of note, the absolute neutrophil count (aNeu) was considered a useful predictive tool for thrombosis among patients classified as low-risk according to the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia. Among PV patients, those with thrombosis showed significantly higher hematocrit and aNeu than did those without thrombosis. As a thrombosis-associated factor, the neutrophil ratio was slightly but significantly elevated in patients with ET. This myeloid skew might reflect a higher value of JAK2 V617F allelic frequency in patients with ET with thrombosis; this was not clarified in JSH-MPN-R18. Further accumulation of evidence, including genetic information for JAK2 and other passenger mutations, is warranted.
RESUMEN
We report a case of therapy-related myelodysplastic syndrome (MDS), which developed 9 years after autologous peripheral blood stem cell transplantation (PBSCT) for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). A 65-year-old male was diagnosed with PTCL-NOS. After 6 cycles of the CHOP (cyclophosphamide [CPA], doxorubicin, vincristine, and prednisone) regimen, he achieved a first complete response (CR). He relapsed 33 months later and received salvage chemotherapy, which consisted of the CHASE regimen (CPA, high-dose cytarabine, dexamethasone, and etoposide). During the recovery phase of the first cycle of CHASE, his peripheral blood stem cells (PBSCs) were harvested and frozen in 2 bags. After 2 courses of CHASE, he underwent autologous PBSCT, which involved the use of the LEED preconditioning regimen (melphalan, CPA, etoposide, and dexamethasone) and one of the frozen bags. This resulted in a second CR. At 39 months after PBSCT, he relapsed with a tumor in his right arm. After it was resected, he received eight cycles of brentuximab vedotin and 45 Gy of involved-field irradiation concurrently and achieved a third CR. Nine years after autologous PBSCT, he was diagnosed with MDS with excess blasts 2 (MDS-EB-2). His disease progressed to acute myeloid leukemia after 2 courses of azacitidine therapy. He successfully underwent a second autologous PBSCT involving the busulfan and melphalan preconditioning regimen and the other frozen bag, which had been stored for 9 years. He has been in complete cytogenetic remission for 1 year since the second autologous PBSCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Linfoma de Células T Periférico , Síndromes Mielodisplásicos , Masculino , Humanos , Anciano , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/tratamiento farmacológico , Etopósido , Melfalán/uso terapéutico , Trasplante Autólogo/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida , Dexametasona/uso terapéutico , Síndromes Mielodisplásicos/etiología , Síndromes Mielodisplásicos/terapia , Resultado del Tratamiento , Terapia CombinadaRESUMEN
We report a case of donor-derived diffuse large B-cell lymphoma (DLBCL), which developed 5 years after stem cell transplantation from a human leukocyte antigen (HLA)-haploidentical donor for acute myeloid leukemia (AML). A 51-year-old male was diagnosed with AML with variant KMT2A translocation involving t(6;11)(q13;q23). After 12 cycles of azacitidine treatment, fluorescence in situ hybridization (FISH) for KMT2A split signal indicated that 94% of his bone marrow (BM) cells were positive. He underwent peripheral blood stem cell transplantation (PBSCT) from his HLA-haploidentical son. The preconditioning regimen consisted of fludarabine, busulfan, melphalan, and antithymocyte globulin (ATG). The graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and short-term methotrexate. On day 28, KMT2A FISH analysis indicated that he had achieved a complete response (CR). He continued to receive tacrolimus for the limited type of cutaneous chronic GVHD. Five years after the transplantation, positron emission tomography/computed tomography (PET/CT) showed an abdominal tumor. The tumor was diagnosed as DLBCL without Epstein-Barr virus. BM aspiration revealed the infiltration of lymphoma cells with t(8;14)(q24;q32). Chimerism analysis showed that both the peripheral blood (PB) and abdominal lymphoma cells were of donor origin. After 4 cycles of salvage chemotherapy, PET/CT showed that a CR had been achieved. He underwent a second PBSCT from an HLA-identical unrelated donor. The preconditioning regimen and GVHD prophylaxis were the same as those for the first PBSCT without ATG. The patient's PB revealed complete second donor-type chimerism, and the patient has maintained a CR since the second transplantation.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Linfoma de Células B Grandes Difuso , Suero Antilinfocítico/uso terapéutico , Azacitidina/uso terapéutico , Busulfano/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Antígenos HLA , Trasplante de Células Madre Hematopoyéticas/métodos , Herpesvirus Humano 4 , Humanos , Hibridación Fluorescente in Situ , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Melfalán/uso terapéutico , Metotrexato/uso terapéutico , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tacrolimus/uso terapéutico , Acondicionamiento Pretrasplante/métodosRESUMEN
The presence of a JAK2 V617F or JAK2 exon 12 mutation is one of the three major criteria listed for the diagnosis of polycythemia vera (PV) in the 2017 World Health Organization Classification. However, a nationwide study has not yet been conducted in Japan since the discovery of JAK2 mutations. Therefore, the Japanese Society of Hematology (JSH) retrospectively analyzed the clinical characteristics of 596 Japanese patients with PV diagnosed between April 2005 and March 2018. Among the 473 patients with complete data on JAK2 mutations available, 446 (94.3%) and 10 (2.1%) were positive for the JAK2 V617F and JAK2 exon 12 mutations, respectively. During a median follow-up of 46 months (range: 0-179 months), 47 (7.9%) deaths occurred. The major causes of death were secondary malignancies (23.4%), acute leukemia (12.8%), non-leukemic progressive disease (10.6%) and thrombotic (6.4%) and hemorrhagic complications (6.4%). Thrombotic and hemorrhagic events occurred during the clinical course in 4.0% (n = 24) and 3.5% (n = 21) of patients, respectively. These results show that the international PV prognostic score (age, venous thrombosis and leukocytosis) is applicable to Japanese patients with PV.
Asunto(s)
Hematología , Policitemia Vera , Trombosis , Humanos , Policitemia Vera/complicaciones , Japón/epidemiología , Janus Quinasa 2/genética , Estudios Retrospectivos , Trombosis/etiología , MutaciónRESUMEN
The hypomethylating agent azacitidine (AZA) significantly extends overall survival (OS) in patients with higher risk myelodysplastic syndromes (MDS), when compared with other conventional care regimens, including supportive care and low-dose and intensive chemotherapy. However, the effects of 5- and 7-day treatment schedules of AZA (AZA-5 and AZA-7, respectively) on the OS of MDS patients had not been compared prospectively. We started a phase 3 trial comparing the effects of AZA-7 and AZA-5 on MDS patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-T). However, this trial was prematurely terminated because of poor recruitment. Using all data, there was no significant difference in the OS of patients between AZA-7 (92 patients) and AZA-5 (95 patients), with the 2-year OS rates of AZA-7 and AZA-5 at 36.4% and 25.8%, respectively (P = 0.293). Adverse event profiles were similar between the two groups. Interestingly, data of the centrally diagnosed RAEB and RAEB-T cases showed that AZA-7 significantly prolonged the time to leukemia transformation compared with AZA-5 (P = 0.022), confirmed by multivariate analysis. Although this trial could not provide definite evidence, the results support the use of AZA-7 for RAEB and RAEB-T. (UMIN Clinical Trials Registry UMIN000009633).
Asunto(s)
Anemia Refractaria con Exceso de Blastos , Azacitidina , Síndromes Mielodisplásicos , Anemia Refractaria con Exceso de Blastos/tratamiento farmacológico , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Azacitidina/administración & dosificación , Azacitidina/efectos adversos , Humanos , Síndromes Mielodisplásicos/tratamiento farmacológicoRESUMEN
We conducted a large-scale, nationwide retrospective study of Japanese patients who were diagnosed with essential thrombocythemia based on the diagnostic criteria in the World Health Organization classification. We investigated clinical characteristics, survival rates, and the incidence of thrombohemorrhagic events as well as risk factors for these events. A total of 1152 patients were analyzed in the present study. Median age at diagnosis was 65 years, the median platelet count was 832 × 109/L, and the positive mutation rates of JAK2V617F, CALR, and MPL were 62.8, 25.1, and 4.1%, respectively. Compared with European and American patients, Japanese patients were more likely to have cardiovascular risk factors and less likely to have systemic symptoms including palpable splenomegaly. Thrombocytosis was identified as a risk factor for hemorrhagic events and prognosis, but not for thrombotic events. The prognostic factors and risk classifications reported in Europe and the United States were generally applicable to Japanese patients. Regarding transformations, secondary myelofibrosis progressed in a time-dependent manner, but progression to acute leukemia was low in "true" ET patients. Skin cancers were less common and gastrointestinal cancers more common as secondary malignancies in Japanese patients, suggesting ethnic differences.
Asunto(s)
Trombocitemia Esencial/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/epidemiología , Adulto JovenRESUMEN
Acute lymphoblastic leukemia (ALL) is a common neoplasm in children, but less frequent in adults. Since information on clinical features and genetics of adult ALL in Japan is limited, we analyzed 215 subjects aged 16-65 years with untreated ALL enrolled in the Fukuoka Blood & Marrow Transplant Group studies ALL MRD 2002 and 2008. The prevalence of ALL was bimodal, with the larger group aged 56-65 years. Immunophenotypic characterization showed B-lineage is more frequent than T-lineage ALL (78.6 vs 13.0%), with age-related differences. The proportion with BCR-ABL1 rearrangement increased progressively with age, up to 55.7% among subjects aged over 56-65 years. Rearrangements involving the KMT2A gene, ETV6-RUNX1, and TCF3-PBX1 were rare in this study cohort. The overall incidence of hyperdiploidy was only 1.7%, and there were no cases with hypodiploidy. Overall survival varied by age and cytogenetics. Older subjects and those with BCR-ABL1 tended to have inferior outcomes. In this epidemiological study of Japanese adult ALL, the majority of subjects had B-lineage ALL, the T-cell phenotype was most frequent in those aged 16-25, and BCR-ABL1 rearrangement was very common, with prevalence increasing with age. These types of adult ALL are potentially manageable with targeted therapies.
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Aberraciones Cromosómicas , Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Adolescente , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Tasa de SupervivenciaRESUMEN
We report a case of hepatosplenic T-cell lymphoma (HSTL) transplanted from an HLA-haploidentical daughter. A 51-year-old man was referred due to liver function test abnormalities and fever. He was confirmed to have γδ-type HSTL by bone marrow and liver biopsies. He was treated with five cycles of a CHOP regimen. Although metabolic complete response (CR), as defined by positron emission tomography, was achieved, his bone marrow still contained tumor cells on polymerase chain reaction (PCR). He underwent transplantation using unmanipulated peripheral blood stem cells from his HLA-haploidentical daughter. The preconditioning regimen consisted of ï¬udarabine, melphalan, busulfan and antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and short-term methotrexate. Neutrophil engraftment was achieved on day 14. His bone marrow exhibited a completely female phenotype by ï¬uorescence in situ hybridization, and no lymphoma cells were detected by PCR on day 30. Although he developed grade II acute GVHD on day 47, it was successfully treated by prednisolone. He has a limited type of skin chronic GVHD and still receives oral immunosuppressive therapy. He remains in CR four years after transplantation.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Neoplasias Hepáticas/terapia , Linfoma de Células T/terapia , Trasplante Haploidéntico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Antígenos HLA/análisis , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Inmunosupresores/uso terapéutico , Neoplasias Hepáticas/patología , Linfoma de Células T/patología , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Prednisolona/uso terapéutico , Neoplasias del Bazo/patología , Neoplasias del Bazo/terapia , Tacrolimus/uso terapéutico , Trasplante Haploidéntico/métodos , Resultado del Tratamiento , Vincristina/uso terapéuticoRESUMEN
OBJECTIVE: We investigated whether minimal residual disease (MRD) status in adult patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) is useful for decision on clinical indications for allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We prospectively monitored MRD after induction and consolidation therapy in adult patients with Ph-negative ALL. RESULTS: Among 103 adult ALL patients enrolled, 59 were Ph-negative, and MRD status was assessed in 51 patients. The probability of 3-year overall survival (OS) and disease-free survival (DFS) was 69% (95%CI 54-80) and 50% (95%CI 36-63), respectively. Patients who were MRD-negative after induction therapy (n = 15) had a significantly better 3-year DFS compared with those who were MRD-positive (n = 30; 73% vs 41%, P = 0.018). Patients who were MRD-positive after induction but became MRD-negative after consolidation chemotherapy C in the first course (n = 11) showed a significantly worse 3-year DFS compared with patients who were MRD-negative after induction chemotherapy A in the first course (45% vs 73%, P = 0.025). CONCLUSIONS: These results indicate that DFS of about 70% can be expected in MRD-negative patients after induction therapy, and the patients did not benefit from HSCT in 1CR. This study was registered with the UMIN Clinical Trials Registry (UMIN-CTR), number UMIN000001519.
Asunto(s)
Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Adulto , Anciano , Quimioterapia de Consolidación , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Quimioterapia de Inducción , Masculino , Persona de Mediana Edad , Neoplasia Residual/genética , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Estudios Prospectivos , Administración de la Seguridad , Translocación Genética , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Trasplante de Células Madre Hematopoyéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Mieloma Múltiple , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto , Anciano , Autoinjertos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Neoplasia Residual , Trasplante AutólogoRESUMEN
This prospective, multicenter phase I/II study of unmanipulated HLA-haploidentical reduced-intensity stem cell transplantation using a low dose of anti-T lymphocyte globulin (ATG) and steroid was conducted in 5 institutions in Japan. Thirty-four patients with hematologic malignancies who were in an advanced stage or at a high risk of relapse at the time of transplantation were enrolled. Among them, 7 patients underwent transplantation as a second transplantation because of relapse after the previous allogeneic stem cell transplantation. The conditioning regimen consisted of fludarabine, busulfan, and ATG (Fresenius, 8 mg/kg), and graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methylprednisolone (1 mg/kg). All patients except 1 (97.1%) achieved donor-type engraftment. Rapid hematopoietic engraftment was achieved, with neutrophils > .5 × 10(9)/L on day 11 and platelets > 20 × 10(9)/L on day 17.5. Treatment was started for ≥grade I GVHD, and the cumulative incidences of acute grade I and grade II to IV GVHD were 27.5% and 30.7%, respectively. The incidence of chronic GVHD (extensive type) was 20%. Fourteen patients (41.2%) had a relapse. The cumulative incidence of transplantation-related mortality at 1 year after transplantation was 26.5%. The survival rate at day 100 was 88.2%. The survival rates at 1 year for patients with complete remission (CR)/chronic phase (n = 8) and non-CR (n = 26) status before transplantation were 62.5% and 42.3%, respectively. In the multivariate analysis, non-CR status before transplantation was the only factor significant prognostic factor of increased relapse (P = .0424), which tended to be associated with a lower survival rate (P = .0524). This transplantation protocol is safe and feasible, if a suitable donor is not available in a timely manner. As the main cause of death was relapse and not GVHD, more intensified conditioning or attenuation of GVHD prophylaxis and/or donor lymphocyte infusion may be desirable for patients with non-CR status.
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Suero Antilinfocítico/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Busulfano/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Esteroides/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Adulto , Suero Antilinfocítico/administración & dosificación , Suero Antilinfocítico/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Busulfano/efectos adversos , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Esteroides/efectos adversos , Vidarabina/efectos adversos , Vidarabina/uso terapéuticoRESUMEN
Polymerase chain reaction (PCR)-negative molecular complete remission (mCR) can be induced by stem cell transplantation in some patients with multiple myeloma (MM) and is associated with long-term progression-free survival (PFS). The detection of molecular minimal residual disease (MRD), however, requires fresh or frozen materials for designing clone-specific primers, which are not always readily available. In this study, we used DNA extracted from archival bone marrow (BM) slides for PCR to detect MRD in 50 patients with MM who received various induction therapies and autologous peripheral blood stem cell transplantation (ASCT). Clonotype-specific immunoglobulin (Ig) H PCR primers were prepared for 32 of 50 cases (64%) using BM slides, and for 9 of 14 cases (64%) using fresh BM cells. DNA in peripheral blood stem cell autografts of the 22 patients who achieved at least a partial response after ASCT was subjected to PCR to amplify clonotype-specific rearranged IgH gene sequences. The median PFS of the eight patients with MRD-positive autografts was 18 months, whereas that of 14 patients with MRD-negative autografts was not reached at a median follow-up of 27 months (p = 0.012). Post-ASCT PFS of the four patients who achieved mCR was 100% at a median follow-up of 47 months. These results indicate that archival BM slides can serve as a source of DNA for preparing clonotype-specific primers for MRD monitoring in patients with MM whose cryopreserved myeloma cells are not available for DNA preparation. Our results also suggest that patients with MM who received MRD-negative autografts and achieved mCR have a long PFS.
Asunto(s)
Médula Ósea/patología , Cartilla de ADN/genética , Mieloma Múltiple/diagnóstico , Neoplasia Residual/diagnóstico , Reacción en Cadena de la Polimerasa , Adulto , Anciano , Femenino , Genes de las Cadenas Pesadas de las Inmunoglobulinas/genética , Técnicas de Preparación Histocitológica , Humanos , Inmunoglobulinas/genética , Masculino , Persona de Mediana Edad , Mieloma Múltiple/genética , Neoplasia Residual/genética , Valor Predictivo de las Pruebas , Pronóstico , Estudios RetrospectivosRESUMEN
B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma (BCLu-DLBCL/CHL), also known as gray-zone lymphoma, has overlapping clinical and biological characteristics of both diffuse large B-cell lymphoma and classical Hodgkin lymphoma (CHL). These lymphomas are typically associated with mediastinal disease, and extranodal involvement is rare. In the present report, we describe a case of a 78-year-old woman with BCLu-DLBCL/CHL found to have extranodal lesions and no evidence of mediastinal disease. Although biopsy specimens were histologically similar to nodular sclerosis CHL, the tumor cells were positive for CD30 and mature B-cell markers, such as CD20, CD79a, PAX5, BOB.1, and OCT-2, but negative for CD15. Furthermore, the patient had extranodal lesions and an increased level of soluble IL-2 receptor. These findings are unusual in CHL. Therefore, we diagnosed the patient with BCLu-DLBCL/CHL. She received adriamycin, bleomycin, vincristine, and dacarbazine therapy and exhibited partial response. Some cases without mediastinal disease, such as our case, have been reported; however, these cases are rare and further studies are required.
Asunto(s)
Neoplasias Abdominales/diagnóstico por imagen , Enfermedad de Hodgkin/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Enfermedades del Mediastino/diagnóstico por imagen , Neoplasias Abdominales/patología , Anciano , Diagnóstico Diferencial , Femenino , Enfermedad de Hodgkin/patología , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Linfoma de Células B Grandes Difuso/patología , CintigrafíaRESUMEN
Imatinib was the first BCR-ABL tyrosine kinase inhibitor to become clinically available. In this study, we retrospectively evaluated the long-term efficacy of low-dose imatinib (final maintenance dose <300 mg per day) due to intolerance, in comparison to optimal-dose imatinib (≥300 mg per day) in patients with Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase. The Kaplan-Meier estimates of the median time to complete cytogenetic response, major molecular response, and complete molecular response were longer for 31 patients receiving low-dose imatinib (360, 1360, and 1420 days, respectively) than 74 patients receiving optimal-dose imatinib (170, 420, and 720 days, respectively). However, the differences in response shrank over time and progression-free survival were comparable between the two groups. These findings suggest that long-term treatment with low-dose imatinib is an acceptable alternative for patients with intolerance to the optimal dose.
Asunto(s)
Antineoplásicos/administración & dosificación , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Piperazinas/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Benzamidas , Niño , Femenino , Humanos , Mesilato de Imatinib , Leucemia Mieloide de Fase Crónica/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
This study was conducted as a prospective, multicenter trial to evaluate the efficacy and safety of micafungin as an empirical therapy for suspected invasive fungal infections (IFIs), including febrile neutropenia (FN), and to evaluate the usefulness of ß-D: -glucan (BG) and Aspergillus galactomannan (GM) antigen in patients with hematologic diseases. A total of 121 patients were enrolled and assessed for safety, and 119 were examined for clinical efficacy. The main underlying diseases were acute myeloid leukemia (38.0%), acute lymphoblastic leukemia (18.2%), and malignant lymphoma (18.2%). The median initial daily dose and duration of micafungin treatment were 150 mg/day and 13 days, respectively. The overall response rate for suspected IFIs (n = 119), based on four composite endpoints, including baseline IFI, breakthrough IFIs (proven and probable), survival, and premature discontinuation, was 79.0%. In addition, the response rate for FN (n = 81), based on these four endpoints as well as defervescence during neutropenia, was 39.5%. Breakthrough IFIs (proven, probable, and possible) occurred in five patients during micafungin treatment. All of these patients were positive for either BG or GM before the breakthrough IFIs. The incidence of adverse events (AEs) associated with micafungin was 10.7% and most were mild. The majority of AEs were liver dysfunction. These results indicate the effectiveness and safety of micafungin as an empirical therapy for suspected IFIs, including FN, and the usefulness of monitoring both BG and GM to detect breakthrough IFIs.
Asunto(s)
Antifúngicos/efectos adversos , Equinocandinas/efectos adversos , Neoplasias Hematológicas/complicaciones , Lipopéptidos/efectos adversos , Micosis/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/uso terapéutico , Antígenos Bacterianos/sangre , Aspergilosis/complicaciones , Aspergilosis/diagnóstico , Aspergilosis/tratamiento farmacológico , Aspergilosis/prevención & control , Candidiasis Invasiva/complicaciones , Candidiasis Invasiva/diagnóstico , Candidiasis Invasiva/tratamiento farmacológico , Candidiasis Invasiva/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Diagnóstico Precoz , Equinocandinas/uso terapéutico , Femenino , Galactosa/análogos & derivados , Humanos , Leucemia Mieloide Aguda/complicaciones , Lipopéptidos/uso terapéutico , Linfoma/complicaciones , Masculino , Mananos/sangre , Micafungina , Persona de Mediana Edad , Micosis/complicaciones , Micosis/diagnóstico , Micosis/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Adulto Joven , beta-Glucanos/sangreRESUMEN
Thyroid MALT lymphoma is an extremely rare malignancy believed to arise against a background of Hashimoto's thyroiditis. Rituximab is a monoclonal antibody directed against B cell specific antigen CD20. Recently, there have been reports that rituximab is effective for autoimmune thyroid diseases such as Graves' disease as well as for treatment of B cell malignant lymphoma. We present the changes in thyroid autoantibodies in Hashimoto's thyroiditis after rituximab administration for 3 cases of thyroid MALT lymphoma. Case 1 had been taking levothyroxine and was diagnosed with thyroid MALT lymphoma. She was treated with rituximab monotherapy, and her thyroid enlargement improved. Anti-thyroid peroxidase antibody (TPOAb) turned negative after rituximab monotherapy, and TSH levels decreased with the same levothyroxine dosage. Case 2 was diagnosed with recurrent thyroid MALT lymphoma after chemotherapy (CHOP). He suffered from leg sensory disturbance because of vincristine sulfate. The patient was treated with rituximab. TPOAb decreased, but did not turn negative. TSH levels were within normal range during the disease course, but TSH levels were low in comparison with before rituximab therapy. Case 3 was diagnosed with thyroid MALT lymphoma after radiation therapy on the neck for laryngeal cancer. Thyroid enlargement improved after rituximab monotherapy, and thyroid autoantibody levels decreased. TSH increased transiently after radiation therapy, but TSH decreased gradually without levothyroxine after rituximab monotherapy. We report 3 cases in which thyroid autoantibody levels in Hashimoto's thyroiditis decreased after rituximab monotherapy for thyroid MALT lymphoma, but it is controversial whether thyroid dysfunction due to Hashimoto's thyroiditis is restored.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Enfermedad de Hashimoto/inmunología , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Glándula Tiroides/inmunología , Neoplasias de la Tiroides/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Enfermedad de Hashimoto/radioterapia , Humanos , Yoduro Peroxidasa/inmunología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Prednisona/uso terapéutico , Rituximab , Glándula Tiroides/patología , Tiroxina/uso terapéutico , Vincristina/uso terapéuticoRESUMEN
Sixty-six B-cell lymphoma patients were treated with a CHOP-based chemotherapy containing rituximab (R-CHOP-like regimen). Immune reconstitution was assessed by measuring lymphocyte subsets and immunoglobulins. Fifty-five patients (83.3%) underwent six cycles of the R-CHOP-like regimen. CD19(+) and CD20(+) cells were completely eliminated from the peripheral blood after one cycle of the R-CHOP-like regimen; they were detected again 6 months after the therapy. One year after the therapy, B-cell numbers recovered to their level at diagnosis and almost doubled 2 years after the therapy. The lowest numbers of CD3(+) , CD8(+) and CD56(+) cells were seen after three cycles of the regimen, but continued to increase until 1 year after the therapy, remaining stable thereafter. CD4(+) T-cells were at their lowest after six cycles of the regimen and recovered slowly for 2 years after the therapy; however, their numbers were still lower than that at diagnosis. Immunoglobulins decreased over six cycles of the R-CHOP-like regimen and then recovered gradually for 2 years after the therapy. The percentage of IgG, IgA and IgM 2 years after the therapy compared with those at diagnosis was 93.9%, 90.1%, 76.3%, respectively. Twelve infectious complications occurred which consisted of three febrile neutropenia, three Herpes Zoster, two tympanitis, two Pneumocystis jiroveci pneumonia and two hepatitis B virus reactivation. B-cells required 1 year and CD4(+) T-cells and immunoglobulins needed 2 years to recover after the therapy.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/inmunología , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Femenino , Humanos , Inmunoglobulinas/sangre , Subgrupos Linfocitarios/inmunología , Linfoma de Células B/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Recurrencia , Rituximab , Vincristina/administración & dosificación , Vincristina/uso terapéuticoRESUMEN
We report two cases of Pneumocystis jiroveci pneumonia (PCP) with CD20(+) B-cell lymphoma. They were treated by several courses of CHOP-based chemotherapy containing rituximab. We confirmed by flow cytometric analysis that both of them completely lost CD19(+) and CD20(+) B-cells from their peripheral blood after the first course of chemotherapy. They were successfully treated with Trimethoprim-sulfamethoxazole (TMP-SMX) after the diagnosis of PCP by polymerase chain reaction (PCR). We overviewed CD20(+) B-cell lymphoma patients treated with CHOP-based regimens from 1997 until 2005 in our hospital. We treated 114 patients with and 121 patients without rituximab. Five patients in the group with rituximab developed interstitial pneumonia (IP). Two of them were confirmed to have PCP and the other three were suspected cases ; however, no patients with IP were seen in the group without rituximab. We strongly suggest the necessity of PCP prophylaxis with oral TMP-SMX when treating B-cell lymphoma patients with chemotherapy containing rituximab.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfoma no Hodgkin/tratamiento farmacológico , Pneumocystis carinii , Neumonía por Pneumocystis/inducido químicamente , Anciano , Antiinfecciosos/uso terapéutico , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Ciclofosfamida/efectos adversos , Doxorrubicina/efectos adversos , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Neumonía por Pneumocystis/tratamiento farmacológico , Reacción en Cadena de la Polimerasa , Prednisona/efectos adversos , Rituximab , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Vincristina/efectos adversosRESUMEN
Epstein-Barr virus (EBV) is the pathogen that most commonly triggers infection-associated hemophagocytic lymphohistiocytosis (HLH) and ectopically infects CD8(+) T cells in EBV-associated HLH (EBV-HLH). We recently described an EBV-HLH patient who had a clonally expanded population of EBV-infected CD8(+) T cells with CD5 down-regulation. To determine whether this finding could serve as a useful marker for EBV-HLH, we investigated 5 additional patients. We found a significant increase in the subpopulation of CD8(+) T cells with CD5 down-regulation and bright human leukocyte antigen (HLA)-DR expression in all patients with EBV-HLH but not in patients with infectious mononucleosis or in control subjects. Such T cells were frequently found to be larger cells that stained positive for a specific T cell receptor VB. We also demonstrated that those cells were the major cellular target of EBV, and their numbers progressively declined in parallel with the serum ferritin levels. All together, our findings reveal the immunophenotypic characteristics of EBV-infected CD8(+) T cells and may provide a valuable tool for the diagnosis of EBV-HLH.
Asunto(s)
Antígenos CD5/biosíntesis , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , Infecciones por Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/patogenicidad , Linfohistiocitosis Hemofagocítica/inmunología , Linfohistiocitosis Hemofagocítica/virología , Niño , Preescolar , Regulación hacia Abajo , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Antígenos HLA-DR/biosíntesis , Herpesvirus Humano 4/inmunología , Humanos , Lactante , Masculino , Receptores de Antígenos de Linfocitos T/biosíntesis , Adulto JovenRESUMEN
Sixty-six adult patients with hematologic malignancies underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) without T cell depletion. The patients were preconditioned with a reduced intensity regimen, and tacrolimus was used for graft-versus-host disease (GVHD) prophylaxis. Successful engraftment occurred in 60 patients (90.1%) and graft rejection in only 4 patients (6.1%). Among the 60 engrafted patients, only 5 developed severe (grade III or IV) acute GVHD. Twenty patients, including 19 relapse-free patients were alive at a median follow-up of 48 months (range 6-77 months). The overall survival (OS) at 6 years was 29.3%. The OS of 45 patients < 60 years of age was 43.6%, which was superior to that of 21 patients who were 60 years of age and older (9.5%) (P < 0.01). The OS of 11 patients from human leukocyte antigen (HLA) 1 locus-mismatched donors (63.6%) was higher than that of 28 patients from HLA 3 loci-mismatched donors (12.5%) (P < 0.01). Organ injury and infection were the main causes of mortality. Notably, immunosuppressive therapy could be successfully stopped in 9 patients transplanted from HLA 2 or 3 loci-mismatched donors with a median duration of 45 months (range 5-71 months). These data suggest that haplo-HSCT is a promising treatment for patients who need urgent allogeneic transplantation but lack HLA-identical family donors.