Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carmustina , Citarabina , Etopósido , Humanos , Linfoma/terapia , Melfalán , Supervivencia sin Progresión , Trasplante de Células Madre , Acondicionamiento Pretrasplante , Trasplante AutólogoRESUMEN
Different authors have explored the feasibility of autografting patients with multiple myeloma (MM) on an outpatient basis. Peg-filgrastim (PEG), a long-acting recombinant G-CSF, has similar efficacy when compared to conventional G-CSF for chemotherapy-induced neutropenia, but little is known about its use in the autologous stem-cell transplantation (ASCT) setting, namely in patients programmed to be autografted on outpatient basis. In this study, we compared therapeutic results in terms of hematopoietic recovery, non-hematologic toxicity, duration of hospitalization and percentage of hospital readmission between patients receiving either conventional G-CSF or PEG. Thirty-eight MM patients (48 autografts) received PEG, given at a single dose of 6 mg at day +5 from stem cell infusion, while 81 (113 autografts) received G-CSF from day + 2 up to stable neutrophil recovery. The conditioning regimen was high dose melphalan in all patients. The median age and the median number of CD34 + cell infused were comparable between the two groups. Overall, a second hospital admission was required in 36 procedures out of 161 (32%). Febrile neutropenia (FN) and severe mucositis were the most frequent causes of hospitalization. There was no statistically significant difference as percentage of hospital readmission is concerned: in the PEG group readmission was needed in 6 out of 48 autografts (12%) as opposed to 30 out of 113 (26%) in the G-CSF subgroup, p: 0.06. The median time of hospital stay for readmitted patients was identical for the two subgroups (9 days vs. 9 days, p: 0.94). Finally, one case of transplant related mortality occurred in the whole patient series (0.6%). In conclusion, ASCT on an outpatient basis is feasible and safe in patients with MM, the majority of whom are manageable at home. The administration of single dose PEG results in no different outcome in terms of safety and efficacy as compared to 8 days of G-CSF.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/cirugía , Trasplante de Células Madre/métodos , Anciano , Femenino , Filgrastim , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Polietilenglicoles , Proteínas Recombinantes/uso terapéutico , Trasplante AutólogoRESUMEN
Acute myeloid leukaemia (AML) secondary to myelodysplastic syndrome (MDS) is characterized by poor prognosis, namely in older patients. The combination of fludarabine (F) with cytarabine (ARA-C) ± G-CSF was proven as effective in patients with poor risk AML. The efficacy and toxicity of a regimen including F + ARA-C as sequential continuous infusion (CI-FLA) in 64 untreated patients aged >60 years, in which AML arose after a previous MDS, was investigated. Median age was 67 years (61-81). In patients achieving CR, an additional course, followed by G-CSF to mobilize CD34+ cells and subsequent autologous stem cell transplantation (ASCT) were programmed. Overall, 43 patients (67%) achieved complete remission (CR). There were 10 induction deaths (16%), while 11 patients (17%) were refractory to induction treatment. Thirty-four patients (79% of remitters) were eligible for the consolidation and 30 were monitorized for the mobilization of CD34+ cells, collection being successful in 20 of them (67%). Median number of CD34+ cells/kg collected was 6.8 × 10E6. Thirteen patients (20% of the whole population) received ASCT. Median disease free survival (DFS) and overall survival (OS) were 10 and 9 months, respectively. Survival at 5 years is projected to 15%. The only parameter significantly related to either DFS duration or OS duration was unfavourable cytogenetics, which did significantly influence also CR achievement. CI-FLA is effective in elderly patients with AML secondary to previously diagnosed MDS. Best results are achievable in the subgroup of patients with diploid karyotype.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide/terapia , Síndromes Mielodisplásicos/complicaciones , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Combinada , Citarabina/administración & dosificación , Citarabina/efectos adversos , Diarrea/inducido químicamente , Supervivencia sin Enfermedad , Femenino , Humanos , Infusiones Intravenosas , Leucemia Mieloide/etiología , Masculino , Persona de Mediana Edad , Inducción de Remisión , Trasplante Autólogo , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/análogos & derivadosRESUMEN
Relapse still occurs in approximately 20-30% of patients with acute promyelocytic leukemia (APL) and, after achievement of second complete remission (CR), the optimal strategy is still controversial. We describe therapeutic results from a series of 13 patients autografted in second molecular remission (MR) by a molecular negative apheresis product. In all patients, the disease was confirmed at the molecular level and all had received the GIMEMA/AIDA protocol, achieving molecular remission at the end of consolidation. Relapse was hematological in 12 cases and molecular in one. After consolidation with chemotherapy, all patients achieved MR and received a further course plus granulocyte-colony stimulating factor as mobilizing therapy. A median of 7.6×10(6) (range 2.7-10) CD34-positive cells/kg were collected. In all cases, molecular evaluation of the apheresis product was negative for the promyelocytic leukemia/retinoic acid receptor alpha gene. No case of transplant-related mortality was recorded. No maintenance or consolidation therapy after autologous stem cell transplantation (ASCT) was given to any patient. After a median follow-up of 25 months from ASCT, 10 patients are alive in sustained MR, while two relapsed after ASCT and died in the setting of refractory disease; one patient achieved a third CR and is waiting for allogeneic SCT. These results suggest that ASCT performed with a molecularly negative graft in APL patients in second MR offers a valid chance for achieving a cure. Such an approach should also be considered in relapsed patients with an HLA-compatible donor, namely in those with a first CR lasting more than one year or in unfit or elderly individuals.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Promielocítica Aguda/terapia , Recurrencia Local de Neoplasia/terapia , Terapia Recuperativa/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Leucemia Promielocítica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Trasplante Autólogo , Adulto JovenRESUMEN
The strategy named double induction (DI) in acute myeloid leukemia (AML) consists of two courses of chemotherapy irrespective of the degree of cytoreduction in the bone marrow (BM) after the first course, unless severe complications prohibit its application. We describe treatment results from a series of 33 patients in whom DI was adopted only after demonstration of persistence of more than 10% blast cells at day 15 (D15) examination of BM. All patients received as induction idarubicin, cytarabine, and etoposide. As second induction, we administered the combination of fludarabine, intermediate dose cytarabine, and Granulocyte colony stimulating factor (G-CSF). The median blast count at D15 was 30 (15-90). Overall, 30 of 33 patients were judged as eligible to receive DI, reasons for exclusion being in all cases active infection in the context of severe pancytopenia. Nineteen patients (63%) had unfavorable karyotype and 11 (37%) normal karyotype; seven of these had Fms-like tyrosine kinase gene internal tandem duplication (FLT3/ITD) mutation. Overall, complete remission (CR) was achieved in 20/30 patients (67%), while eight patients (27%) were refractory and two died of infectious complications. All refractory patients had unfavorable cytogenetics. All patients achieving CR were programmed to receive allogeneic stem cell transplantation (allo-SCT), which was actually performed in 11 patients. Our study suggest that D15 driven DI represents a feasible and effective therapeutic strategy in young adult AML patients, improving therapeutic results and not compromising feasibility of allo-SCT. When compared with conventional DI, it offers the potential to avoid unnecessary toxicity in a consistent proportion of patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Crisis Blástica/terapia , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Crisis Blástica/genética , Crisis Blástica/mortalidad , Crisis Blástica/patología , Médula Ósea/patología , Aberraciones Cromosómicas , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Idarrubicina/administración & dosificación , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Mutación , Inducción de Remisión , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Trasplante Homólogo , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados , Adulto JovenRESUMEN
Mutations of the nucleophosmin gene (NPM1), in the absence of concurrent FLT3-internal tandem duplication (FLT3-ITD) have impressive prognostic value in patients with acute myelogenous leukemia (AML), carrying normal karyotype (NK). In this study we describe treatment results from a series of 19 patients with NPM+/FLT3- autografted in first complete remission (CR) after conditioning with a regimen, named BuI, based on high-dose continuous infusion of idarubicin and Busulfan. Ninety-nine consecutive patients (median age of 54 years) with NK AML autografted in first CR were analyzed. Nineteen of 99 patients (19%) had NPM1 mutation in the absence of FLT3 mutations. The control group, accounting for 80 patients, included 16 cases (15%) with both mutations, 10 (12%) with FLT3/ITD mutation and no NPM mutation, and 54 (68%) in whom neither NPM1 nor FLT3 mutations were detectable. The median overall survival (OS) for the whole patient population was 34 months, the median disease-free survival (DFS) was 22 months. Median OS and DFS were significantly longer for patients with isolated NPM1 mutation as opposed to controls (OS: not reached versus 25 months, P = .02; DFS: not reached versus 16 months, P = .007, respectively). Of interest, patients with isolated NPM1 mutation had a better outcome in terms of either OS or DFS compared to the group of 16 NMP1+/FLT3+ patients. In conclusion, our study suggest that BuI regimen results in favorable clinical outcome in patients with isolated NPM1 mutation, and could be investigated in a randomized study versus other regimes or repeated courses of high dose cytosine-arabinoside.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutación , Proteínas Nucleares/genética , Trasplante de Células Madre , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Busulfano/administración & dosificación , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Idarrubicina/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Nucleofosmina , Pronóstico , Resultado del Tratamiento , Adulto Joven , Tirosina Quinasa 3 Similar a fms/genéticaRESUMEN
The t(11;14)(q13;q32) is a hallmark of mantle cell lymphoma. It has been found less frequently in other lymphoproliferative disorders, such as B-prolymphocytic leukemia, plasma cell leukemia, chronic lymphocytic leukemia, and multiple myeloma. Here, we describe a patient with acute myeloid leukemia (AML), categorized as M5b according to French-American-British classification, in which conventional cytogenetic analysis revealed a karyotype with t(11;14)(q13;q32). Fluorescence in situ hybridization analyses demonstrated no rearrangement of the immunoglobulin heavy-chain (IGH) (14q32) locus as well as of the cyclin D1 (CCND1) gene, suggesting that this is not the typical t(11;14) resulting from the CCND1/IGH fusion. The changes in the 11q13 region have been described in both myeloid and lymphoid neoplasm with different chromosomes serving as donors in translocation, but to the best of our knowledge, never with the chromosome 14.
Asunto(s)
Ciclina D1/genética , Cadenas Pesadas de Inmunoglobulina/genética , Leucemia Mieloide Aguda/genética , Translocación Genética , Médula Ósea/patología , Femenino , Humanos , Cariotipificación , Leucemia Mieloide Aguda/patología , Persona de Mediana EdadAsunto(s)
Aberraciones Cromosómicas , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Tirosina Quinasa 3 Similar a fms/genética , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Cariotipificación , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Tasa de SupervivenciaRESUMEN
The current study aimed to evaluate the efficacy and toxicity of a combination of intravenous (iv) busulfan (Bu) and continuous infusion Idarubicin (IDA) as a conditioning regimen to autologous haematopoietic stem cell transplantation (ASCT) in patients with acute myeloid leukaemia (AML). The protocol included IDA at 20 mg/sqm daily as 3 days continuous infusion (from day -13 to -11) and intravenous BU at 3.2 mg/kg daily from day -5 to -2. Patients aged over 60 years received a reduced schedule (2 days IDA and 3 days BU at the same dose). Twenty-five patients with a median age of 51 years (28-72) were enrolled. All patients received peripheral blood stem cells (PBSC). The median interval between diagnosis and ASCT was 4 months. The median number of CD34+ cells infused was 5.9 x 10E6/kg. The median number of days to PMN >500/cmm and platelets >20000/cmm was 10 and 13, respectively. In order to perform a comparison in terms of haematological and non haematological toxicity, a group of 30 patients, who were previously autografted after conditioning with IDA and oral Bu was considered. Selection of factors for a matched pair analysis included median age, percentage of subjects aged over 60 years, median CD34+ cell received, cytogenetic and molecular findings and per cent of secondary AML. As compared to previous series, the occurrence of severe mucositis was dramatically reduced (80% vs. 12%, p < 0.0001). In addition, need and duration of total parenteral nutrition (TPN), iv antibiotic therapy and hospitalization were also significantly reduced. We conclude that replacement of oral with intravenous BU results in a more favourable toxicity profile. A longer follow-up is required to assess a potential advantage in terms of disease free survival (DFS).