RESUMO
BACKGROUND AIMS: While donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) in the recipient before transplantation are associated with graft failure in cord-blood transplantation (CBT), effects of DSAs other than against HLA-A, -B or -DRB1 on transplantation outcomes remained poorly understood. METHODS: We retrospectively analyzed 567 single-unit CBT recipients to evaluate impact of DSAs against HLA-DP and -DQ on CBT outcomes. RESULTS: Among 143 recipients (25.2%) who had anti-HLA antibodies, nine harbored DSAs against HLA-DP or -DQ. DSAs against HLA-DP or -DQ were associated with a significantly lower neutrophil engraftment rate (55.6% versus 91.8%, P = 0.032) and with a marginally lower platelet engraftment rate (46.7% versus 75.3%, P = 0.128) at day 100 after transplantation, compared with patients without anti-HLA antibodies. Time to neutrophil and platelet engraftment in patients with DSAs for HLA-DP or -DQ was significantly longer than that in patients without anti-HLA antibodies (median, 25 versus 21 days, P = 0.002 in neutrophil; median 61 versus 46 days, P = 0.014 in platelet). Cumulative incidence of bacterial infection at day 100 was significantly greater (88.9% versus 57.1%, P = 0.024), and re-transplant-free survival was marginally lower (55.6% versus 76.8%, P = 0.132) in patients with DSAs against HLA-DP or -DQ, compared with those without anti-HLA antibodies. These findings suggest that DSAs against HLA-DP or -DQ lead to unfavorable engraftment, which may increase risk of bacterial infection, and reduce survival soon after CBT. CONCLUSIONS: Our results suggest the importance of evaluating DSAs against HLA-DP and -DQ in recipients before selecting CB units.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Antígenos HLA , Antígenos de Histocompatibilidade Classe I , Antígenos de Histocompatibilidade Classe II , Doadores de Tecidos , Antígenos HLA-DP , Sobrevivência de EnxertoRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is detectable in nasopharyngeal specimens for up to 12-20 days regardless of the presence of chronic diseases in patients. We report a case of prolonged SARS-CoV-2 infection that lasted for more than eight weeks. The patient had persistent lymphopenia after receiving six cycles of bendamustine and rituximab (BR) therapy for follicular lymphoma; the last chemotherapy session was completed nine months before admission. The first nasopharyngeal specimen (NPS) for the SARS-CoV-2 polymerase chain reaction assay tested positive for the N501Y variant five weeks before admission. The patient's general and respiratory conditions gradually worsened; therefore, he was admitted to our hospital, and the same SARS-CoV-2 variant was subsequently identified on admission. Treatment for coronavirus disease was initiated, and the patient's condition improved; however, the NPS tested positive on day 15. The patient was discharged on day 28 and was instructed to isolate at home for a month. Hence, possible prolonged SARS-CoV-2 shedding should be considered in patients who receive BR therapy.
Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Cloridrato de Bendamustina/uso terapêutico , Humanos , Masculino , RNA Viral , Rituximab/efeitos adversos , Eliminação de Partículas ViraisRESUMO
BACKGROUND: BK polyomavirus (BKV) can cause hemorrhagic cystitis (HC) in immunocompromised patients after hematopoietic stem cell transplantation (HSCT). It remains unclear whether nosocomial BKV infections occur. During a 9-month period, an increase in BKV-associated HC (BKV-HC) cases was observed at our institution. AIM: The BKV-HC cluster population was compared with populations of HSCT patients from before and after the BKV-HC cluster to evaluate whether nosocomial BKV transmission had occurred. METHODS: A retrospective analysis was carried out to assess the risk of patients developing BKV-HC after HSCT. The background data of the cluster patients were compared with those of the patients who underwent HSCT before or after the cluster, and the collected BKV isolates were serotyped. RESULTS: BKV-HC involving grade ≥2 hematuria occurred in six of 15 HSCT recipients during a 9-month period. The incidence of BKV-HC was significantly higher in this period than in the other periods (p = 0.0014). There were no significant differences in the patients' background data between the cluster and non-cluster periods, including in terms of risk factors for BKV-HC. Serotype analyses of BKV revealed that the BKV detected in the urine samples from four of the six BKV-HC patients belonged to subtype Ic. The gene sequences of these four BKV exhibited >99.5% homology. CONCLUSION: Our study suggests that nosocomial BKV infections may occur after HSCT. Although many cases of BKV-HC are caused by the reactivation of a latent virus, it is necessary to employ appropriate hygiene measures when cases of BKV-HC occur.
Assuntos
Vírus BK , Cistite , Transplante de Células-Tronco Hematopoéticas , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Vírus BK/genética , Cistite/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Infecções por Polyomavirus/epidemiologia , Estudos Retrospectivos , Infecções Tumorais por Vírus/epidemiologiaRESUMO
Cancer patients occasionally have anemia with high mean corpuscular volume in addition to iron deficiency anemia. Secondary autoimmune hemolytic anemia (AIHA) following cancer is also observed with low frequency. To date, no causal mechanisms for these disease states have been reported. Here, we present the case of an 80-year-old woman with AIHA that was resistant to prednisolone. Further examinations revealed primary adenocarcinoma of the sigmoid colon and primary squamous cell carcinoma in the right lung. After resections of these tumors, her anemia partially improved until a colon cancer-derived metastatic tumor was detected in the left lung. Immunoprecipitation of erythrocyte membrane proteins with an autoantibody followed by mass spectrometry/Western blotting identified band 3 as the target of the autoantibody. Immunohistochemical analysis revealed ectopic expression of band 3 in the colon adenocarcinoma. To our knowledge, this is the first report that identifies the cause in a case of anemia without bleeding in a cancer patient and that defines a mechanism underlying secondary AIHA following cancer progression.
Assuntos
Adenocarcinoma/complicações , Anemia Hemolítica Autoimune/imunologia , Proteína 1 de Troca de Ânion do Eritrócito/imunologia , Neoplasias do Colo/complicações , Expressão Ectópica do Gene/imunologia , Adenocarcinoma/patologia , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Autoantígenos/imunologia , Carcinoma de Células Escamosas/patologia , Neoplasias do Colo/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Primárias Múltiplas/patologiaRESUMO
Sezary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma and is chemo-resistant. Allogeneic hematopoietic stem cell transplantation is a promising therapy for SS; however, relapse is common. Therapeutic options after relapse have not been established. We managed an SS patient with hematological relapse within one month after transplantation. After discontinuation of immunosuppressants, she achieved complete remission and remained relapse-free. The chimeric analyses of Tcells showed that the full recipient type became complete donor chimera after immunological symptoms. This clinical course suggested that discontinuation of immunosuppressants may result in a graftversus- tumor effect, leading to the eradication of lymphoma cells.
RESUMO
Umbilical cord blood transplantation (UCBT) is often associated with delayed neutrophil and platelet recovery. Engraftment failure is another major obstacle. Several factors influence these serious complications, including the numbers of total nucleated cells (TNCs) and CD34+ cells which have been used as reliable factors for selecting UCB units for transplantation. However, whether both factors are reliable indices of the hematopoietic stem cell (HSC) activity of UCB units remains unknown. To evaluate the quality of UCB units, we quantified the actual number of transplantable CD34+CD133+ HSCs (tHSCs) residing in UCB units. The number of tHSCs was not correlated with the numbers of TNCs or CD34+ cells. These results strongly suggest that neither factor reflects the numbers of tHSCs residing in UCB units. To validate the significance of the number of tHSCs, further analysis is required to determine whether the number of tHSCs residing in UCB units is useful as a new indicator for the quality assessment of UCB units.
Assuntos
Antígeno AC133/metabolismo , Antígenos CD34/metabolismo , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Biomarcadores , Contagem de Células Sanguíneas , Transplante de Células-Tronco de Sangue do Cordão Umbilical/normas , Humanos , Imunofenotipagem , Garantia da Qualidade dos Cuidados de SaúdeAssuntos
Anticorpos Monoclonais Humanizados , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma de Células T do Adulto , Aloenxertos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacocinética , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Humanos , Leucemia-Linfoma de Células T do Adulto/imunologia , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
Primary central nervous system lymphoma (PCNSL) is more difficult to treat than other lymphomas. Recently, it has been suggested that high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is effective for treating PCNSL. In the present study, we retrospectively analyzed 12 patients with PCNSL at our hospital. Five young patients with good performance status (PS) received upfront ASCT. The conditioning regimen prior to ASCT with busulfan ï¼ cyclophosphamide ï¼ etoposide showed good prognosis (complete remission rate of 100%). In addition, the PS improved in patients treated with high-dose chemotherapy followed by ASCT, while it worsened in those treated without ASCT. Further investigations are needed to clarify inclusion/exclusion criteria and optimize conditioning regimens for ASCT.
Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Linfoma/terapia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo , Resultado do TratamentoAssuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Linfoma Plasmablástico/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistência a Medicamentos , Resistencia a Medicamentos Antineoplásicos , Infecções por Vírus Epstein-Barr , Feminino , Soronegatividade para HIV , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Linfoma Plasmablástico/diagnóstico por imagem , Linfoma Plasmablástico/tratamento farmacológico , Linfoma Plasmablástico/virologia , Indução de Remissão , Condicionamento Pré-Transplante/métodosRESUMO
A 49-year-old female from China was referred to our hospital after endocervical polypectomy. Twenty years before admission, after the birth of her first child, an intrauterine device (IUD) had been inserted due to the one-child policy in China. She had noticed abnormal vaginal bleeding with a foul smell 3 years before admission. Then the IUD was removed and a polyp was found at the IUD contact site. Two months before admission, endocervical polypectomy was performed. Lymphoma was suspected by histological examination and she was referred to our hospital. Further examination confirmed the diagnosis of primary uterine diffuse large B-cell lymphoma (DLBCL). Subsequently, a combination of three cycles of R-CHOP regimen and involved-field radiation therapy was performed, followed by maintenance therapy with five cycles of rituximab. She has remained in complete remission for over 1 year. This case suggests that chronic inflammation induced by prolonged IUD insertion may contribute to the development of primary uterine lymphoma. To the best of our knowledge, this is the first reported case of DLBCL associated with prolonged IUD insertion.
Assuntos
Dispositivos Intrauterinos , Linfoma Difuso de Grandes Células B/diagnóstico , Neoplasias Uterinas/diagnóstico , Biópsia , Terapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Dispositivos Intrauterinos/efeitos adversos , Linfoma Difuso de Grandes Células B/etiologia , Linfoma Difuso de Grandes Células B/terapia , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Pólipos , Resultado do Tratamento , Neoplasias Uterinas/etiologia , Neoplasias Uterinas/terapiaRESUMO
To test the feasibility of mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis in Japanese patients, we conducted two multicenter prospective phase II trials of allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA-matched related donors (MRD group) with MMF and cyclosporine or HLA 7-8/8 allele-matched unrelated bone-marrow donors (URD group) with MMF and tacrolimus. The cumulative incidences of grade II-IV acute GVHD on day 100, which was the primary endpoint in these trials, were 45.0% (90% CI 25.8-62.5) and 25.8% (90% CI 13.9-39.5) in the MRD (n = 20) and URD (n = 31) groups, respectively. The rates of 3-year overall survival and non-relapse mortality were 80.0 and 15.0% in the MRD group and 74.2 and 6.5% in the URD group, respectively. GVHD prophylaxis with MMF may lead to a lower incidence of severe mucositis and faster neutrophil engraftment compared to that with methotrexate. A pharmacokinetics study of mycophenolic acid (MPA) showed that a relatively higher plasma concentration of MPA was associated with a lower incidence of acute GVHD. In conclusion, the results of these studies suggest that GVHD prophylaxis with MMF may be useful as an alternative in Japanese patients who may benefit from faster engraftment or less severe mucositis after allogeneic HSCT.
Assuntos
Inibidores de Calcineurina/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade , Ácido Micofenólico/administração & dosagem , Adulto , Idoso , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/imunologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mucosite/prevenção & controle , Irmãos , Transplante Homólogo , Doadores não Relacionados , VoluntáriosRESUMO
A 73-year-old woman was admitted to our hospital because of pancytopenia. Bone marrow aspiration showed increased cellularity with no dysplastic change. Laboratory tests revealed increased reticulated erythrocytes and reticulated platelets, positive direct Coombs test, and hemolysis. These findings led to the diagnosis of Evans syndrome. Relatively decreased mature neutrophils in the bone marrow aspirate raised the possibility of autoimmune neutropenia. Antineutrophil antibody was detected by the 6 cell-lineage immunofluorescence test, consistent with the diagnosis of autoimmune neutropenia. The patient had no underlying diseases, and was therefore considered to have idiopathic autoimmune pancytopenia. Due to rapid progression of the disease, prednisolone was administered at an initial dose of 0.5 mg/kg per day and the pancytopenia improved promptly.
Assuntos
Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/tratamento farmacológico , Glucocorticoides/uso terapêutico , Pancitopenia/tratamento farmacológico , Prednisolona/uso terapêutico , Trombocitopenia/diagnóstico , Trombocitopenia/tratamento farmacológico , Idoso , Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/patologia , Biópsia , Linhagem da Célula , Progressão da Doença , Feminino , Humanos , Pancitopenia/etiologia , Pancitopenia/patologia , Trombocitopenia/complicações , Trombocitopenia/patologiaRESUMO
We report cases of three patients of refractory ascites without other fluid retention that occurred around five months after allogeneic hematopoietic stem cell transplantation (allo-HSCT). All three patients expired and postmortem examinations revealed unexpected liver fibrosis lacking histological evidences of graft-versus-host-disease (GVHD). The three patients showed normal hepatic function and size before transplantation. During their clinical courses, serum biochemistry test showed no elevation of hepatic enzymes and bilirubin; however, imaging studies demonstrated hepatic atrophy at the onset of ascites. One of the liver specimens showed bile obstruction, which could be seen in hepatic damage by GVHD. Although ascites resulting from venoocclusive disease in early phase allo-HSCT is well documented, ascites associated with hepatic fibrosis in late phase allo-HCST has not been reported. Further clinico-pathological studies on similar patients should be required to ascertain refractory ascites associated with liver fibrosis after allo-HSCT.
RESUMO
B-cell lymphoproliferative disorder (B-LPD) is generally characterized by the proliferation of Epstein-Barr virus (EBV)-infected B lymphocytes. We here report the development of EBV-negative B-LPD associated with EBV-reactivation following antithymocyte globulin (ATG) therapy in a patient with aplastic anemia. The molecular autopsy study showed the sparse EBV-infected clonal T cells could be critically involved in the pathogenesis of EBV-negative oligoclonal B-LPD through cytokine amplification and escape from T-cell surveillances attributable to ATG-based immunosuppressive therapy, leading to an extremely rare B-cell-rich T-cell lymphoma. This report helps in elucidating the complex pathophysiology of intractable B-LPD refractory to rituximab.
RESUMO
UNLABELLED: Prognosis for adult patients with acute lymphoblastic leukemia (ALL) has been reported to be approximately 35% to 50%, even after allogeneic stem cell transplantation (allo-SCT). We previously reported retrospective analyses of a conditioning regimen of medium-dose etoposide, cyclophosphamide (CY), and total body irradiation (TBI) before allo-SCT for ALL. To prospectively analyze the efficacy of this conditioning regimen, we conducted a trial prospectively. METHODS: The eligibility criteria of this study were as follows: diagnosis of ALL, aged between 15 and 50 years, in complete remission, and first SCT from HLA serologically matched donor. The primary endpoint of this study was event-free survival at 1 year after SCT, and the events were defined as death and relapse. RESULTS: Fifty eligible patients were treated, and the median age of the patients was 33.5 years. Nineteen patients were Philadelphia chromosome-positive, and 47 were in first complete remission at SCT. All patients achieved neutrophil engraftment. Grade 3 to 4 acute graft-versus-host disease and extensive chronic graft-versus-host disease developed in 4 patients and 18 patients, respectively. No patient died within 100 days after SCT. One-year event-free survival was 76.0%, and 1-year overall survival was 80.0%. The cumulative incidences of relapse and non-relapse mortality at 1-year after SCT were 10.0% and 14.0%, respectively. CONCLUSIONS: Medium-dose etoposide + CY + TBI is an effective conditioning before allo-SCT for adult patients with ALL, enabling good disease control without an increase in nonrelapse mortality. A phase 3 trial comparing this regimen with the standard CY + TBI regimen for adult patients with ALL is warranted.
RESUMO
A 57-year-old Japanese man was admitted to our hospital with diarrhea, weight loss and malabsorption. Due to a high serum IgA level, we suspected α-heavy chain disease (α-HCD). However, no monoclonal IgA was detected on protein electrophoresis or immunofixation. Immunohistochemical staining of intestinal biopsy specimens showed proliferation of CD138(+)IgA(+) cells, compatible with a diagnosis of α-HCD. Most α-HCD patients exhibit M-proteins in the serum on electrophoresis or immunoelectrophoresis; however, some patients lack detectable M-proteins, similar to our patient. Therefore, when α-HCD is suspected based on the clinical features, immunohistochemistry is required to make a diagnosis.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Diarreia/etiologia , Imunoglobulina A/sangue , Imuno-Histoquímica , Doença Imunoproliferativa do Intestino Delgado/diagnóstico , Síndromes de Malabsorção/etiologia , Proteínas do Mieloma/metabolismo , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Eletroforese , Humanos , Doença Imunoproliferativa do Intestino Delgado/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prednisona/administração & dosagem , Resultado do Tratamento , Vincristina/administração & dosagem , Redução de PesoRESUMO
Core binding factor acute myeloid leukemia is known to have a favorable prognosis, however, there have been no detailed analyses on prognostic factors after first relapse. Using a nationwide database, we retrospectively analyzed core binding factor acute myeloid leukemia patients who relapsed after being treated with chemotherapy alone during their first complete remission. Of a total of 397 patients who were diagnosed with core binding factor acute myeloid leukemia, 208 experienced a first relapse, and analyses were performed in 139 patients for whom additional data were available. In the entire cohort, the overall survival rate after relapse was 48% at 3 years. By multivariate analysis, younger age at diagnosis, a longer interval before relapse, and inv(16) were shown to be independently associated with better survival after relapse. Although there was no significant difference in survival after relapse between patients who underwent allogeneic hematopoietic cell transplantation and those who did not in the overall series of relapsed patients, we found that transplantation significantly improved survival among patients who had t(8;21) (54% versus 26% at 3 years, P=0.002). In addition, among patients with t(8;21), those who had different cytogenetics at relapse had a significantly improved survival after transplantation, while those who had same cytogenetics did not. We showed that the prognosis differs significantly and optimal treatment strategies may vary between groups of patients with core binding factor acute myeloid leukemia with different cytogenetic profiles at relapse. These findings may help to guide therapeutic decisions after first relapse.
Assuntos
Fatores de Ligação ao Core , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Adolescente , Adulto , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Adulto JovemRESUMO
A 60-year-old myelodysplastic syndrome patient underwent tandem cord blood transplantation. The primary cord blood graft was rejected, and human herpesvirus 6 (HHV6) encephalitis developed after engraftment of secondary cord blood. Polyuria and adipsic hypernatremia were observed during treatment of the encephalitis. The patient died of bacteremia caused by methicillin-resistant Streptococcus epidermis. HHV6 infection in the posterior pituitary was confirmed on autopsy, as was infection of the hippocampus, but not of the hypothalamus. This is the first case report of central diabetes insipidus caused by an HHV6 posterior pituitary infection demonstrated on a pathological examination.
Assuntos
Anemia Refratária com Excesso de Blastos/cirurgia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Diabetes Insípido Neurogênico/etiologia , Encefalite Viral/complicações , Herpesvirus Humano 6/isolamento & purificação , Doenças da Hipófise/complicações , Neuro-Hipófise/virologia , Complicações Pós-Operatórias/etiologia , Infecções por Roseolovirus/complicações , Aloenxertos , Antivirais/uso terapêutico , Bacteriemia/etiologia , Bacteriemia/microbiologia , Encefalite Viral/tratamento farmacológico , Encefalite Viral/virologia , Evolução Fatal , Feminino , Rejeição de Enxerto , Humanos , Hospedeiro Imunocomprometido , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Neutropenia/induzido quimicamente , Neutropenia/complicações , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/virologia , Neuro-Hipófise/fisiopatologia , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/virologia , Reoperação , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/microbiologia , Microangiopatias Trombóticas/etiologia , Condicionamento Pré-Transplante/efeitos adversosRESUMO
To analyse the outcome of adult patients who developed a first relapse of acute lymphoblastic leukaemia (ALL), we collected the clinical data of 332 patients with Philadelphia-chromosome (Ph) negative ALL, aged 16-65 years, who relapsed after first complete remission (CR1) between 1998 and 2008 in 69 institutions all over Japan, including 58 patients who relapsed after allogeneic haematopoietic stem cell transplantation (Allo-HSCT) in CR1. The overall survival (OS) was 43·4% at 1 year, and 16·3% at 5 years from relapse in patients who received chemotherapy alone in CR1. Among patients who relapsed after chemotherapy alone in CR1, 123 (52·5%) achieved a second remission (CR2) following salvage chemotherapy, of whom 62 subsequently underwent Allo-HSCT during CR2. Allo-HSCT in CR2 was significantly associated with better OS. Moreover, the type of salvage chemotherapy influenced OS from relapse. A doxorubicin, vincristine, and predonisone-based (AdVP-type) regimen was related to better OS in patients with longer CR1 (more than 1 year), but was related to worse OS in patients with shorter CR1. In conclusion, the prognosis of patients with relapsed Ph-negative ALL is poor. Allo-HSCT after a first relapse could improve the prognosis. Selection of the optimal salvage chemotherapy might depend on the duration of CR1.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Recidiva , Indução de Remissão , Estudos Retrospectivos , Terapia de Salvação , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
t(8;22)(p11;q11) is a rare but recurrent chromosome translocation that has been reported in 11 cases of myeloproliferative neoplasm or B-acute lymphoblastic leukemia. This translocation results in an in-frame fusion of FGFR1 on 8p11 and BCR on 22q11, and causes constitutive activation of the tyrosine kinase of the BCR/FGFR1 chimera protein. Here, we report the twelfth case of hematological tumor bearing t(8;22)(p11;q11). The bone marrow showed hypoplastic and tri-lineage dysplasia with 24.4% abnormal cells. The abnormal cells were not defined as myeloid or lymphoid morphologically, lacking a myeloperoxidase reaction. Flow cytometric analysis of the bone marrow cells revealed that the abnormal cells expressed CD13, CD33, CD34, and CD19, and that a fraction of the abnormal cells was positive for CD10. Southern blot analysis of the bone marrow cells showed rearrangement of the immunoglobulin heavy chain gene, a genetic hallmark of B-cell differentiation. Previously reported cases with t(8;22)(p11;q11) suggested an association between myeloid and B-lymphoid tumors, whereas other chromosome translocations involving FGFR1 on 8p11 showed a link between myeloid and T-lymphoid tumors. Our observation supports that t(8;22)(p11;q11) might define a dual myeloid and B-lymphoid disorder.