RESUMEN
Acute myeloid leukemia (AML) is the most common leukemia in adults. In spite of the most recent discoveries about the molecular landscape of this disease, the treatment of elderly and unfit young patients continues to be a great challenge. The hypomethylating agents (HMA) still represent an effective therapeutic option for these categories, especially for the low-risk subgroups. We report the case of a young patient with NPM1mut-AML who underwent a first cycle of intensive induction treatment, achieving a complete remission, but suffered from a serious life-threatening neurologic toxicity. Due to the ineligibility to further lines of intensive chemotherapy, we decided to consolidate the response with azacitidine, administered according to the regular schedule. The minimal residual disease (MRD), monitored through the NPM1 mutation at diagnosis, progressively decreased and became undetectable after 36 cycles of hypomethylating therapy. After 1 year from discontinuation of azacitidine, MRD remains undetectable. Therefore, HMA might still represent a feasible and effective option for patients with low-risk AML, especially when the standard chemotherapy is not indicated, or as maintenance therapy in nontransplantable patients.
Asunto(s)
Azacitidina , Leucemia Mieloide Aguda , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina/uso terapéutico , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Neoplasia Residual/tratamiento farmacológico , Inducción de RemisiónRESUMEN
In Ph- myeloproliferative neoplasms, the quantification of the JAK2V617F transcripts may provide some advantages over the DNA allele burden determination. We developed a q-RT-PCR to assess the JAK2WT and JAK2V617F mRNA expression in 105 cases (23 donors, 13 secondary polycythemia, 22 polycythemia vera (PV), 38 essential thrombocythemia (ET), and 9 primary myelofibrosis (PMF)). Compared with the standard allele-specific oligonucleotide (ASO)-PCR technique, our assay showed a 100 % concordance rate detecting the JAK2V617F mutation in 22/22 PV (100 %), 29/38 (76.3 %) ET, and 5/9 (55.5 %) PMF cases, respectively. The sensitivity of the assay was 0.01 %. Comparing DNA and RNA samples, we found that the JAK2V617F mutational ratios were significantly higher at the RNA level both in PV (p = 0.005) and ET (p = 0.001) samples. In PV patients, JAK2WT expression levels positively correlated with the platelets (PLTs) (p = 0.003) whereas a trend to negative correlation was observed with the Hb levels (p = 0.051). JAK2V617F-positive cases showed the lowest JAK2WT and ABL1 mRNA expression levels. In all the samples, the expression pattern of beta-glucoronidase (GUSB) was more homogeneous than that of ABL1 or ß2 microglobulin (B2M). Using GUSB as normalizator gene, a significant increase of the JAK2V617F mRNA levels was seen in two ET patients at time of progression to PV. In conclusion, the proposed q-RT-PCR is a sensitive and accurate method to quantify the JAK2 mutational status that can also show clinical correlations suggesting the impact of the residual amount of the JAK2WT allele on the Ph- MPN disease phenotype. Our observations also preclude the use of ABL1 as a housekeeping gene for these neoplasms.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , Janus Quinasa 2/genética , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/genética , Trastornos Mieloproliferativos/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Janus Quinasa 2/biosíntesis , Células K562 , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/diagnóstico , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/metabolismo , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/metabolismoRESUMEN
BACKGROUND: Smoldering multiple myeloma (SMM) presents a high risk of progression to symptomatic MM (sy-MM). Herein, we analyzed some predictors of development of sy-MM. In 144 patients with SMM, we also compared the risk of progression predicted by bone marrow plasma cell (BMPC) involvement on the bone marrow biopsy (BMB) versus bone marrow aspirates (BMA). METHODS: From January 1980 to July 2010, 397 patients with SMM observed in 12 centers of the Multiple Myeloma GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) Latium Working Group have been analyzed. At progression to sy-MM, the severity of clinical presentation was graded according to the need of intensive supportive care. RESULTS: After a median follow-up of 135 months, the cumulative incidence of progression rates to sy-MM were 45%, 55%, and 75% at 10, 15, and 20 years, respectively. Hemoglobin ≤12.5 g/dL, monoclonal component ≥2.5 g/dL, and BMPC ≥60% were the only parameters negatively affecting the cumulative incidence of progression. In particular, 10 of 397 (2.5%) patients with BMPC ≥60% had a 5.6-fold increased risk of fast progression (within 2 years), which occurred with severe clinical manifestations in 62% of cases. BMB was more sensitive for the detection of BMPC involvement, even though BMA was a more reliable indicator of a rapid progression to sy-MM. CONCLUSIONS: The highest risk of rapid evolution to sy-MM and the severity of clinical manifestation at the progression suggest that SMM patients with a BMPC ≥60% should be treated soon after diagnosis. Moreover, BMPC is a more reliable index for progression to sy-MM if assessed by BMA.
Asunto(s)
Células de la Médula Ósea/patología , Mieloma Múltiple/diagnóstico , Células Plasmáticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Asintomáticas , Biopsia con Aguja , Médula Ósea/patología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
We analyzed 12 MLL/ENL positive ALL patients consecutively diagnosed between 1999 and 2009. The MLL/ENL fusion was identified in 4/150 (2.6%), 8/993 (0.8%), and 0/70 of pediatric, adult, and elderly patients, respectively. Eight patients had a WBC count >50 × 10(9) /L. Ten cases had an evaluable immunophenotyping. A B or T precursor ALL occurred in 7 and 3 patients, respectively. Eleven/12 patients (92%) achieved CR. At 48 months, overall survival and event-free survival rates were 73.3% and 67%, respectively. At CR, a parallel RT-PCR evaluation of the MLL/ENL expression was available in 5 cases. Of these latter, 2 tested MLL/ENL-negative and 3 positive. The minimal residual disease molecular monitoring showed that MLL/ENL status did not correlate with outcome. In fact, all the 2 PCR-negative and 1 of the 3 PCR-positive cases relapsed. Further, a MLL/ENL expression, not preceding a relapse, was detected several times during the follow-up of five long-survivors. In conclusion, also in adults, the MLL/ENL fusion identifies a rare leukemic entity with a favorable prognosis. The observed inconsistency between the clinical cure and the presence of detectable MLL/ENL transcript suggests the existence of a MLL/ENL-expressing "preleukemia" stem cells, similar to what demonstrated for the AML1/ETO-positive leukemia setting.
Asunto(s)
Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Proteínas de Fusión Oncogénica/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Factores de Elongación Transcripcional/metabolismo , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Regulación Leucémica de la Expresión Génica , Humanos , Lactante , Masculino , Persona de Mediana Edad , Proteína de la Leucemia Mieloide-Linfoide/genética , Neoplasia Residual/diagnóstico , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Inducción de Remisión , Ciudad de Roma , Análisis de Supervivencia , Factores de Elongación Transcripcional/genética , Adulto JovenRESUMEN
We compared 2-[fluorine-18] fluoro-2-deoxy-d-glucose PET-CT and contrast-enhanced computed tomography (CECT) in 62 consecutive patients with newly diagnosed Hodgkin Lymphoma (HL), aiming to provide evidences that may spare CECT from the staging procedures of HL patients. Among a total of 1448 nodal sites examined, disease involvement was detected in 232 (16%) and 280 (19.3%) nodal areas by CECT and PET-CT, respectively (P < 0.01). Sensitivity of CECT in detecting disease involvement ranged from 0% for internal mammary region (7 cases) and Waldayer's ring (1 case) to 100% for mediastinum. A total of 248 extranodal areas were examined. CECT and PET-CT identified disease involvement in 19 (7.7%) and 25 (10.1%) extranodal areas, respectively (P = n.s). Compared to PET-CT, CECT detected a lower number of cases with bone and/or bone marrow involvement (P = 0.05), whereas no differences were detected at the level of lung. By contrast, CECT identified liver lesions in four patients versus three identified by PET-CT. In comparison to CECT, PET-CT upstaged 6 patients (9.7%) and downstaged 1 patient (1.6%). We showed that PET-CT modified treatment strategy in five (8.1%) cases not only as a result of stage advancement (2 cases) but also of a different prognostic stratification in patients with localized disease (3 cases), due to the better sensitivity in detecting nodal involvement. In conclusion, our data, confirm the superiority of PET-CT in detecting disease involvement at diagnosis of HL, and further supports the possibility to replace CECT with PET-CT in the initial staging of HL.
Asunto(s)
Fluorodesoxiglucosa F18 , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adulto , Biopsia , Médula Ósea/patología , Femenino , Enfermedad de Hodgkin/terapia , Humanos , Aumento de la Imagen , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto JovenRESUMEN
Since very few unusual BCR/ABL fusion transcripts in chronic myeloid leukemia have been reported, no clear evidence exists concerning their clinical and prognostic implications. We describe here a CML case with normal karyotype at standard cytogenetics and an atypical e6a2 BCR/ABL fusion transcript, presenting at diagnosis isolated thrombocytosis and mild leukopenia; the patient, who was tested negative for JAK2 mutation, obtained a complete response to imatinib. The few previous observations from literature are also reviewed.
Asunto(s)
Janus Quinasa 2/genética , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/diagnóstico , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/tratamiento farmacológico , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/genética , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Trombocitosis/diagnóstico , Adulto , Benzamidas , Rotura Cromosómica , Humanos , Mesilato de Imatinib , Masculino , Resultado del TratamientoAsunto(s)
Antivirales/administración & dosificación , Quimioprevención/métodos , Guanina/análogos & derivados , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/prevención & control , Leucemia Linfocítica Crónica de Células B/complicaciones , Activación Viral , Antineoplásicos/administración & dosificación , Clorhidrato de Bendamustina , ADN Viral/sangre , Guanina/administración & dosificación , Hepatitis B/virología , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Compuestos de Mostaza Nitrogenada/administración & dosificaciónRESUMEN
Although consensus exists relating criteria for the identification of low-risk patients with febrile neutropenia, no clear indication on how to manage these patients has been so far provided particularly in outpatients affected by hematologic malignancies. The feasibility and safety of early discharge was prospectively evaluated in 100 outpatients with hematologic malignancies and febrile neutropenia. A strategy considering the risk-index of the Multinational Association of Supportive Care in Cancer (MASCC) was applied. High-risk patients were entirely managed at hospital. Low-risk patients were early discharged if they were afebrile since 48 h and not on supportive therapy requiring hospitalization. Out of 90 low-risk episodes, in 69 instances (76.7%), patients were discharged after a median of 4 days and continued home therapy with oral cefixime (78%) or other antibiotics. Only five outpatients (7.2%) had fever recurrence. Twenty-one low-risk patients were not early discharged due to worsening conditions (three deaths), need of multiple daily dose therapy, or discharge refuse. No clinical characteristic was able to predict the eligibility for early discharge. The MASCC risk-index is a useful aid in the identification of high-risk febrile neutropenia needing whole in-hospital treatment. As for low-risk patients, hospitalization at least in the first days of fever is required. Cefixime could be included among the oral antibacterial drugs to be used in the outpatient treatment of adult patients with febrile neutropenia.
Asunto(s)
Antiinfecciosos/uso terapéutico , Neoplasias Hematológicas/tratamiento farmacológico , Neutropenia/tratamiento farmacológico , Alta del Paciente/estadística & datos numéricos , Administración Oral , Adolescente , Adulto , Anciano , Antiinfecciosos/administración & dosificación , Infecciones Bacterianas/complicaciones , Cefixima/administración & dosificación , Cefixima/uso terapéutico , Femenino , Fiebre/complicaciones , Neoplasias Hematológicas/patología , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Neutropenia/complicaciones , Neutropenia/patología , Estudios Prospectivos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Tiempo , Resultado del TratamientoRESUMEN
To predict leukemic transformation (LT), we evaluated easily detectable diagnostic parameters in 338 patients with primary myelofibrosis (PMF) followed in the Latium region (Italy) between 1981 and 2010. Forty patients (11.8%) progressed to leukemia, with a resulting 10-year leukemia-free survival (LFS) rates of 72%. Hb (<10g/dL), and circulating blasts (≥1%) were the only two independent prognostic for LT at the multivariate analysis. Two hundred-fifty patients with both the two parameters available were grouped as follows: low risk (none or one factor)=216 patients; high risk (both factors)=31 patients. The median LFS times were 269 and 45 months for the low and high-risk groups, respectively (P<.0001). The LT predictive power of these two parameters was confirmed in an external series of 270 PMF patients from Tuscany, in whom the median LFS was not reached and 61 months for the low and high risk groups, respectively (P<.0001). These results establish anemia and circulating blasts, two easily and universally available parameters, as strong predictors of LT in PMF and may help to improve prognostic stratification of these patients particularly in countries with low resources where more sophisticated molecular testing is unavailable.
Asunto(s)
Anemia/fisiopatología , Transformación Celular Neoplásica/patología , Hemoglobinas/análisis , Células Neoplásicas Circulantes/patología , Mielofibrosis Primaria/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Crisis Blástica , Transformación Celular Neoplásica/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mielofibrosis Primaria/sangre , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Estudios de Validación como AsuntoRESUMEN
OBJECTIVE: The clinical outcome of elderly (≥75years) patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL) is not firmly established because few studies have specifically addressed this issue. In addition, the usefulness of a comprehensive geriatric assessment (CGA) in B-NHL still needs to be deeply explored. MATERIALS AND METHODS: We evaluated the prognostic factors of 73 patients aged ≥75years (median age: 78) with B-NHL treated by clinical judgment with curative anthracycline-based approaches (n=36) or with conservative treatments without anthracyclines (n=37). Analysis of clinical outcomes also included baseline CGA stratification. RESULTS: The curative approaches resulted in a better clinical outcome than conservative approaches [overall response rate: 91.2% vs. 69.7%, P=0.003; 2-year progression-free survival: 47.2% vs. 21.6%, P=0.006; and 2-year overall survival (OS): 58.3% vs 24.3%, P=0.003] with similar safety profiles. Independent of treatment type, patients classified as "fit" and "intermediate" by CGA presented with better OS compared to patients classified as "frail" (P<0.001). Patients classified as "fit" and "intermediate" who were receiving curative treatments presented with a significantly better OS when compared with those treated conservatively on the basis of clinical judgment. A curative anthracycline-based therapy (P=0.048), the response to treatment (P=0.017) and a "frail" condition (P=0.031) were the only factors affecting OS in multivariate analysis. CONCLUSIONS: Present data indicates that even in elderly patients with B-NHL curative anthracycline-based therapies are more effective than conservative approaches. However, choice of treatment should rely more on objective than on subjective parameters. Therefore, further prospective trials are warranted to better define the CGA role in hematopoietic malignancies.
Asunto(s)
Antraciclinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Evaluación Geriátrica/métodos , Linfoma de Células B/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Anciano Frágil , Humanos , Linfoma de Células B/mortalidad , Masculino , Pronóstico , Estudios RetrospectivosAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Rituximab/administración & dosificación , Anciano , Anciano de 80 o más Años , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Prednisona/uso terapéutico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Vincristina/uso terapéuticoRESUMEN
Entecavir and tenofovir disoproxil fumarate are potent and effective antiviral drugs that now represent recommended treatment options for chronic HBV infection. However, no or very limited clinical evidence is currently available on these drugs for the management of HBV reactivation in patients with haematological malignancies. Herein, we report a case of HBV reactivation in a patient with non-Hodgkin's lymphoma following a rituximab-based regimen, and who was successfully treated with a combination antiviral treatment including entecavir and tenofovir disoproxil fumarate.
Asunto(s)
Adenina/análogos & derivados , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antivirales/uso terapéutico , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Organofosfonatos/uso terapéutico , Adenina/uso terapéutico , Combinación de Medicamentos , Femenino , Guanina/uso terapéutico , Virus de la Hepatitis B/fisiología , Humanos , Linfoma no Hodgkin , Persona de Mediana Edad , Rituximab , Tenofovir , Activación ViralAsunto(s)
Crisis Blástica/inducido químicamente , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/efectos adversos , Pirimidinas/efectos adversos , Benzamidas , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Inducción de Remisión/métodos , Terapia Recuperativa/métodosAsunto(s)
Neoplasias Óseas/diagnóstico , Neoplasias Óseas/terapia , Plasmacitoma/diagnóstico , Plasmacitoma/terapia , Tibia/patología , Adolescente , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Resultado del Tratamiento , Adulto JovenRESUMEN
Two cases of acute myeloid leukaemia (AML) with CD2 and CD7 expression associated with diabetes insipidus (DI) as the initial symptom are presented. Both patients had t(3;3)(q21;q26) associated with monosomy 7 and EVI-1 overexpression. No neurohypophysis infiltration was evident. One patient died during induction chemotherapy, the other did not respond to therapy and died with persistent DI. Our findings further support the existence of a distinct AML entity characterized by the presence of DI, abnormalities of chromosome 3q, dysmegakaryopoiesis and poor outcome, and provide evidence of EVI-1 gene involvement. The possible role of chromosome 3q26 abnormalities in determining this peculiar clinical-biological association is emphasized.