RESUMEN
Hodgkin lymphoma (HL) patients who relapse after autologous-stem-cell- transplantation (auto-SCT) have traditionally had a poor prognosis. We analyzed 1781 adult HL patients who relapsed between 2006 and 2017 after a first auto-SCT. The 4-year overall survival (OS) after relapse continuously increased from 32% for patients relapsing in 2006-2008, to 63% for patients relapsing in 2015-2017 (p = 0.001). The improvement over time was predominantly noted in patients who had an early relapse (within 12 months) after auto-SCT (p = 0.01). On multivariate analysis, patients who relapsed in more recent years and those with a longer interval from transplant to relapse had a better OS, whereas increasing age, poor performance status, bulky disease, extranodal disease and presence of B symptoms at relapse were associated with a worse OS. Brentuximab vedotin (BV), checkpoint inhibitors (CPI) and second transplant (SCT2; 86% allogeneic) were used in 233, 91 and 330 patients respectively. The 4-year OS from BV, CPI, and SCT2 use was 55%, 48% and 55% respectively. In conclusion, the outcome after post-transplant relapse has improved significantly in recent years, particularly in the case of early relapse. These large-scale real-world data can serve as benchmark for future studies in this setting.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Inmunoconjugados , Adulto , Brentuximab Vedotina , Enfermedad de Hodgkin/terapia , Humanos , Inmunoconjugados/efectos adversos , Recurrencia Local de Neoplasia/inducido químicamente , Recurrencia Local de Neoplasia/terapia , Estudios Retrospectivos , Trasplante AutólogoRESUMEN
We retrospectively compared outcomes of a large series of adult patients with APL in CR2 receiving alloHSCT (n = 228) or autoHSCT (n = 341) reported to the European Society for Blood and Marrow Transplantation from January 2004 to December 2018. The 2-year cumulative incidence of non-relapse mortality was significantly higher for alloHSCT 17.3% (95% CI 12.5-22.8) compared with autoHSCT 2.7% (95% CI 1.2-5) (p = 0.001), while differences in relapse rate were not significant (28% versus 22.9%; p = 0.28). Leukemia-free survival (LFS) and overall survival (OS) favored autoHSCT with 74.5% (95% CI 69-79.2) and 82.4% (95% CI 77.3-86.5) compared with alloHSCT with 54.7% (95% CI 47.5-61.3) (p = 0.001) and 64.3% (95% CI 57.2-70.6), respectively (p = 0.001 and p = 0.001). Multivariable analysis showed significantly worse LFS after alloHSCT (HR 0.49; 95% CI 0.37-0.67; p < 0.0001), older age (p = 0.001), and shorter time from diagnosis to transplant (p = 0.00015). Similar results were obtained for OS. The study shows that autoHSCT resulted in better survival outcomes (LFS and OS) for APL in CR2. These results were mainly due to reduced NRM in the autoHSCT as compared to alloHSCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Leucemia Promielocítica Aguda , Adulto , Anciano , Humanos , Leucemia Promielocítica Aguda/terapia , Inducción de Remisión , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Trasplante HomólogoRESUMEN
The purpose of this study was to analyze the results of second autologous hematopoietic stem cell transplantation (ASCT2) for patients with relapsed/refractory Hodgkin lymphoma (HL) after a first transplantation (ASCT1). Outcomes for 56 patients receiving an ASCT2 registered in the EBMT database were analyzed. The 4-year cumulative incidences of non-relapse mortality and disease relapse/progression were 5% and 67%, respectively. The 4-year overall survival (OS) and progression-free survival (PFS) were 62% and 28%. In univariate analysis, relapse of HL within 12 months of ASCT1 was associated with a worse OS (35% versus 76%, p = 0.01) and PFS (19% versus 29%, p = 0.059). Chemosensitivity at ASCT2 predicted better outcomes (4-year OS 72% versus 29%, p = 0.002; PFS 31% versus 12%, p = 0.015). This series shows that ASCT2 is a safe procedure and a relatively effective option for patients with late relapses after ASCT1 and with chemosensitive disease who are not eligible for an allogeneic transplant.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Linfoma , Autoinjertos , Supervivencia sin Enfermedad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad de Hodgkin/terapia , Humanos , Recurrencia Local de Neoplasia , Recurrencia , Trasplante de Células Madre , Trasplante AutólogoRESUMEN
The present study aimed at describing the outcome of patients with HIV-associated lymphomas following autologous hematopoietic stem cell transplantation (autoHCT) in the rituximab and combined antiretroviral therapy (cART) era. Eligible for this retrospective study were HIV-positive patients with lymphoma who received autoHCT between 2007 and 2013. A total of 118 patients were included with a median age of 45 years (range 24-66). Underlying diagnoses were diffuse large B cell lymphoma in 47%, Hodgkin lymphoma in 24%, Burkitt lymphoma in 18%, and plasmablastic lymphoma in 7% of patients. Disease status at autoHCT was complete remission in 44%, partial remission (PR) in 38%, and less than PR in 18% of the patients. With a median follow-up of 4 years, 3-year non-relapse mortality, incidence of relapse, progression-free survival (PFS) and overall survival (OS) were 10%, 27%, 63% and 66%, respectively. By multivariate analysis, disease status less than PR but not CD4+ cell count at the time of autoHCT was a significant predictor of unfavorable PFS and OS. In conclusion, in the era of cART and chemoimmunotherapy, the outcome of autoHCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of the HIV infection.
Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/complicaciones , Linfoma/tratamiento farmacológico , Linfoma/terapia , Rituximab/uso terapéutico , Trasplante Autólogo/métodos , Adulto , Anciano , Antirretrovirales/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rituximab/farmacología , Adulto JovenRESUMEN
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) represents the most common genetic subtype of adult ALL (20%-30%) and accounts for approximately 50% of all cases in the elderly. It has been considered the subgroup of ALL with the worst outcome. The introduction of tyrosine kinase inhibitors (TKIs) allows complete hematologic remission virtually in all patients, with improved disease-free survival and overall survival. Nevertheless, the emergence of resistant mutations in BCR-ABL1 may require different TKI strategies to overcome the patient's resistance and disease relapse. Here, we report a Ph+B-ALL case with persistent minimal residual disease (MRD) after treatment with dasatinib. The patient expressed the P190BCR-ABL1 isoform and a novel BCR-ABL1 mutation, p.Y440C. The latter is in the C-terminal lobe of the kinase domain, which likely induces deviations in the protein structure and activity and destabilizes its inactive conformation. The treatment was substituted by bosutinib, which binds to the active conformation of the protein, prior to allogeneic bone marrow transplant to overcome the lack of a complete response to dasatinib. These findings strengthen the importance of BCR-ABL1 mutational screening in Ph+ patients, particularly for those who do not achieve complete molecular remission.
Asunto(s)
Proteínas de Fusión bcr-abl , Regulación Enzimológica de la Expresión Génica , Regulación Leucémica de la Expresión Génica , Leucemia Mielógena Crónica BCR-ABL Positiva , Cromosoma Filadelfia , Adulto , Proteínas de Fusión bcr-abl/biosíntesis , Proteínas de Fusión bcr-abl/genética , Humanos , Isoenzimas/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/enzimología , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , MasculinoRESUMEN
The purpose of this retrospective registry study was to investigate the outcome of autoSCT for primary mediastinal B-cell lymphoma (PMBCL) in the rituximab era, including the effects of eventual post-transplant radiotherapy (RT) consolidation. Patients with PMBCL aged between 18 and 70 years who were treated with a first autoSCT between 2000 and 2012 and registered with the EBMT were eligible. Eighty-six patients with confirmed PMBCL and the full data set required for this analysis were evaluable. Sixteen patients underwent autoSCT in remission after first-line therapy (CR/PR1), 44 patients were transplanted with chemosensitive relapsed or primary refractory disease (CR/PR >1), and 24 patients were chemorefractory at the time of autoSCT. With a median follow-up of 5 years, 3-year estimates of relapse incidence, progression-free survival, and overall survival were 6%, 94%, and 100% for CR/PR1; 31%, 64%, and 85% for CR/PR >1; and 52%, 39%, and 41% for REF, respectively. Whilst there was no significant benefit of post-transplant RT in the CR/PR >1 group, RT could completely prevent disease recurrence post d100 in the refractory group. In conclusion, autoSCT with or without consolidating RT is associated with excellent outcome in chemoimmunotherapy-sensitive PMBCL, whereas its benefits seem to be limited in chemoimmunotherapy-refractory disease.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma de Células B/radioterapia , Linfoma de Células B/cirugía , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/métodos , Adulto , Anciano , Europa (Continente) , Femenino , Humanos , Linfoma de Células B/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Oral busulfan is the historical backbone of the busulfan+cyclophosphamide regimen for autologous stem cell transplantation. However intravenous busulfan has more predictable pharmacokinetics and less toxicity than oral busulfan; we, therefore, retrospectively analyzed data from 952 patients with acute myeloid leukemia who received intravenous busulfan for autologous stem cell transplantation. Most patients were male (n=531, 56%), and the median age at transplantation was 50.5 years. Two-year overall survival, leukemia-free survival, and relapse incidence were 67±2%, 53±2%, and 40±2%, respectively. The non-relapse mortality rate at 2 years was 7±1%. Five patients died from veno-occlusive disease. Overall leukemia-free survival and relapse incidence at 2 years did not differ significantly between the 815 patients transplanted in first complete remission (52±2% and 40±2%, respectively) and the 137 patients transplanted in second complete remission (58±5% and 35±5%, respectively). Cytogenetic risk classification and age were significant prognostic factors: the 2-year leukemia-free survival was 63±4% in patients with good risk cytogenetics, 52±3% in those with intermediate risk cytogenetics, and 37 ± 10% in those with poor risk cytogenetics (P=0.01); patients ≤50 years old had better overall survival (77±2% versus 56±3%; P<0.001), leukemia-free survival (61±3% versus 45±3%; P<0.001), relapse incidence (35±2% versus 45±3%; P<0.005), and non-relapse mortality (4±1% versus 10±2%; P<0.001) than older patients. The combination of intravenous busulfan and high-dose melphalan was associated with the best overall survival (75±4%). Our results suggest that the use of intravenous busulfan simplifies the autograft procedure and confirm the usefulness of autologous stem cell transplantation in acute myeloid leukemia. As in allogeneic transplantation, veno-occlusive disease is an uncommon complication after an autograft using intravenous busulfan.
Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Busulfano/administración & dosificación , Recolección de Datos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Anciano , Trasplante de Médula Ósea/mortalidad , Recolección de Datos/métodos , Europa (Continente)/epidemiología , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Trasplante Autólogo/mortalidad , Adulto JovenRESUMEN
PURPOSE: Plasma cell meningitis is an uncommon neurologic complication of multiple myeloma with a very poor prognosis (median overall survival of 3 months). CASE REPORT: We describe a previously heavy treated 54-year-old caucasian female with Bence Jones multiple myeloma who developed, shortly after a good partial response to a third line therapy, a plasma cell meningitis. Intrathecal chemotherapy was give with achievement of a complete response and improvement of her neurologic status, being alive after more than 6 months of follow-up. CONCLUSION: A high index of suspicion is necessary to diagnose this rae entity since treatment initiation may provide symptomatic relief and improve the quality of life.
Asunto(s)
Meningitis/patología , Mieloma Múltiple/complicaciones , Células Plasmáticas/patología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND AND OBJECTIVES: The role of the Janus kinase 2 V617F (JAK2(V617F)) mutation in the pathogenesis of the various BCR-ABL1-negative myeloproliferative neoplasms (MPNs) remains unclear. Its significance in leukemic transformation is a matter of even greater controversy. The aim of this study was to evaluate both the JAK2(V617F) mutational status of the rare cases in which blast crisis occurred in our institution and the response after intensive treatment. MATERIALS AND METHODS: Between 1999 and 2009, 778 patients received diagnoses of BCR-ABL1-negative MPNs in our center (395 polycythemia vera, 329 essential thrombocythemia, and 45 primary myelofibrosis cases, as well as 9 MPN cases not otherwise classifiable). Of these patients, 7 developed leukemic transformation. The genotyping of the JAK2(V617F) mutation was performed by the amplification-refractory mutation system. RESULTS: Six of the 7 patients were tested for JAK2(V617F) in the chronic phase of their disease, and 3 of these patients were positive for JAK2(V617F). These patients, 2 with polycythemia vera and 1 with essential thrombocythemia, also harbored JAK2(V617F) in the heterozygous state during blast crisis and even after intensive treatment in one of these patients. The other cases that evolved to blast crisis did not harbor the JAK2(V617F) mutation before and after transformation. All 7 patients died despite conventional or supportive treatment. CONCLUSIONS: The transformation of MPNs into acute leukemia is by itself a very rare phenomenon, and so is the persistence of the JAK2(V617F) mutation after blast crisis. In our series, all JAK2(V617F)-positive patients remained positive for this mutation after leukemic transformation, although in the heterozygous state, suggesting that JAK2(V617F) is not essential for transformation in these cases. The fact that all JAK2(V617F)-negative cases remained negative after blast crisis reinforces the theory that other molecular event(s) may play a role in the clonal heterogeneity of MPNs. Owing to the poor outcome of acute myeloid leukemia secondary to MPN, patients should be included in clinical trials of the novel JAK2 inhibitors.
Asunto(s)
Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Janus Quinasa 2/genética , Mutación/genética , Trastornos Mieloproliferativos/enzimología , Trastornos Mieloproliferativos/genética , Anciano , Codón/genética , Femenino , Humanos , Janus Quinasa 2/metabolismo , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/patología , Trastornos Mieloproliferativos/terapia , Resultado del TratamientoRESUMEN
In adults, non-Hodgkin's lymphoma (NHL) is the second most common neoplasm found in the head and neck region after squamous cell carcinoma. Within this region, primary NHL of the nasopharynx is rare. We report the case of a 28-year-old male diagnosed with a B lymphoblastic lymphoma (CD20-; CD79a+; CD3-; CD10+; PAX5+, CyclinD1-; TdT+) of the nasopharynx extending to the deep and superficial structures of the right hemiface, to the skull base with an intracranial component and a small but detectable bone marrow involvement, who was started on chemotherapy with a complete response. To the best of our knowledge, this is the first case of a primary nasopharynx B-LBL in an adult patient with such aggressive regional spread to be reported in the literature.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Adulto , Biopsia , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/patología , Masculino , Inducción de RemisiónRESUMEN
BACKGROUND: Invasive aspergillosis (IA) is a major cause of morbidity and mortality in profoundly neutropenic patients, so early diagnosis is mandatory. AIM: Consecutive patients with hematological malignancies undergoing intensive chemotherapy were screened for IA with two different methods which were compared. METHODS: From October 2000 to August 2003 we tested 1311 serum samples from 172 consecutive patients with a polymerase chain reaction assay and between April 2005 and April 2008 we tested 806 serum samples from 169 consecutive patients with a Galactomannan (GM) test. Bronchoalveolar (BAL) samples were obtained whenever the patient's condition allowed and tested with either method. RESULTS: The serum PCR assay had a sensitivity of 75.0% and a specificity of 91.9% and the serum GM assay had a sensitivity of 87.5% and a specificity of 93.1%, (P > 0.05). The presence of two or more consecutive positive serum samples was predictive of IA for both assays. BAL GM/PCR was positive in some patients without serum positivity and in patients with 2 or more positive serum GM/PCR. CONCLUSIONS: No significant differences between the 2 serum tests were found. The GM assay has the advantage of being standardized among several laboratories and is incorporated in the criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycosis Study Group (EORTC/MSG), however is much more expensive. BAL GM and PCR sampling aids in IA diagnosis but needs further validation studies to differentiate between colonization and true infection in cases where serum GM or PCR are negative.