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1.
Am J Hematol ; 99(6): 1108-1118, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38563187

RESUMEN

We investigated using a custom NGS panel of 149 genes the mutational landscape of 64 consecutive adult patients with tyrosine kinase fusion-negative hypereosinophilia (HE)/hypereosinophilic syndrome (HES) harboring features suggestive of myeloid neoplasm. At least one mutation was reported in 50/64 (78%) patients (compared to 8/44 (18%) patients with idiopathic HE/HES/HEUS used as controls; p < .001). Thirty-five patients (54%) had at least one mutation involving the JAK-STAT pathway, including STAT5B (n = 18, among which the hotspot N642H, n = 13), JAK1 (indels in exon 13, n = 5; V658F/L, n = 2), and JAK2 (V617F, n = 6; indels in exon 13, n = 2). Other previously undescribed somatic mutations were also found in JAK2, JAK1, STAT5B, and STAT5A, including three patients who shared the same STAT5A V707fs mutation and features consistent with primary polycythemia. Nearly all JAK-STAT mutations were preceded by (or associated with) myelodysplasia-related gene mutations, especially in RNA-splicing genes or chromatin modifiers. In multivariate analysis, neurologic involvement (hazard ratio [HR] 4.95 [1.87-13.13]; p = .001), anemia (HR 5.50 [2.24-13.49]; p < .001), and the presence of a high-risk mutation (as per the molecular international prognosis scoring system: HR 6.87 [2.39-19.72]; p < .001) were independently associated with impaired overall survival. While corticosteroids were ineffective in all treated JAK-STAT-mutated patients, ruxolitinib showed positive hematological responses including in STAT5A-mutated patients. These findings emphasize the usefulness of NGS for the workup of tyrosine kinase fusion-negative HE/HES patients and support the use of JAK inhibitors in this setting. Updated classifications could consider patients with JAK-STAT mutations and eosinophilia as a new "gene mutated-entity" that could be differentiated from CEL, NOS, and idiopathic HES.


Asunto(s)
Síndrome Hipereosinofílico , Mutación , Factor de Transcripción STAT5 , Humanos , Síndrome Hipereosinofílico/genética , Síndrome Hipereosinofílico/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Factor de Transcripción STAT5/genética , Janus Quinasa 2/genética , Transducción de Señal , Janus Quinasa 1/genética , Anciano de 80 o más Años , Pirimidinas/uso terapéutico , Adulto Joven
2.
Haematologica ; 108(11): 3068-3085, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37317877

RESUMEN

Hereditary erythrocytosis is a rare hematologic disorder characterized by an excess of red blood cell production. Here we describe a European collaborative study involving a collection of 2,160 patients with erythrocytosis sequenced in ten different laboratories. We focused our study on the EGLN1 gene and identified 39 germline missense variants including one gene deletion in 47 probands. EGLN1 encodes the PHD2 prolyl 4-hydroxylase, a major inhibitor of hypoxia-inducible factor. We performed a comprehensive study to evaluate the causal role of the identified PHD2 variants: (i) in silico studies of localization, conservation, and deleterious effects; (ii) analysis of hematologic parameters of carriers identified in the UK Biobank; (iii) functional studies of the protein activity and stability; and (iv) a comprehensive study of PHD2 splicing. Altogether, these studies allowed the classification of 16 pathogenic or likely pathogenic mutants in a total of 48 patients and relatives. The in silico studies extended to the variants described in the literature showed that a minority of PHD2 variants can be classified as pathogenic (36/96), without any differences from the variants of unknown significance regarding the severity of the developed disease (hematologic parameters and complications). Here, we demonstrated the great value of federating laboratories working on such rare disorders in order to implement the criteria required for genetic classification, a strategy that should be extended to all hereditary hematologic diseases.


Asunto(s)
Policitemia , Humanos , Policitemia/diagnóstico , Policitemia/genética , Policitemia/metabolismo , Prolina Dioxigenasas del Factor Inducible por Hipoxia/genética , Prolina Dioxigenasas del Factor Inducible por Hipoxia/metabolismo , Mutación de Línea Germinal , Secuencia de Bases
3.
Eur J Haematol ; 109(6): 719-727, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36048142

RESUMEN

BACKGROUND: Autoimmune conditions in B-cell lymphomas are frequent. Steroids are standard of care, but many patients require other immunosuppressive agents. Ibrutinib is a Bruton Tyrosine Kinase inhibitor that is approved for B-cell indolent lymphoma treatment. We evaluated the use of ibrutinib in previously treated hematologic immune manifestations associated with B-cell lymphomas. RESULTS: We conducted a retrospective multicentric observational study. Patients presenting with active, relapsed/refractory B-cell lymphoma associated hematological immune manifestation (autoimmune cytopenia, acquired immune-mediated bleeding disorders) were included. Twenty-five patients were identified. Median age at ibrutinib introduction was 69 years (range 44-84) and median number of previous treatment lines before ibrutinib was 2 (1-7). Twenty-two patients (88%) were on concomitant stable treatment at inclusion. Within a median exposure of 8 months (2-35), overall response rate to ibrutinib on immune manifestations was 76% (95% CI, 54.9-90.6); complete response rate 44%. Fourteen patients (63%) were able to be weaned from concomitant treatments. Fourteen patients (56%) presented treatment-related adverse events, mostly Grade 1 or 2. CONCLUSIONS: Ibrutinib in this setting provides good efficacy and safety profile. Clinical trials are needed to define subgroups of patients who will benefit from this strategy and establish its place in the therapeutic arsenal.


Asunto(s)
Enfermedades Autoinmunes , Enfermedades Hematológicas , Leucemia Linfocítica Crónica de Células B , Linfoma de Células B , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Pirimidinas/efectos adversos , Pirazoles/efectos adversos , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas/efectos adversos , Linfoma de Células B/complicaciones , Linfoma de Células B/diagnóstico , Linfoma de Células B/tratamiento farmacológico , Enfermedades Hematológicas/tratamiento farmacológico , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/tratamiento farmacológico
4.
Haematologica ; 106(12): 3100-3106, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34047178

RESUMEN

The aim of this study was to characterize a large series of 154 patients with acute promyelocytic leukemia (median age, 53 years; range, 18-90 years) and evaluate real-life outcome after up-front treatment with arsenic trioxide and all-trans retinoic acid. All patients were included in the prospective NAPOLEON registry (NCT02192619) between 2013 and 2019. The acute promyelocytic leukemia was de novo in 91% (n=140) and therapy-related in 9% (n=14); 13% (n=20) of the patients were older than 70 years. At diagnosis bleeding/hemorrhage was present in 38% and thrombosis in 3%. Complete remission was achieved in 152 patients (99%), whereas two patients (1%) experienced induction death within 18 days after starting therapy. With a median follow-up of 1.99 years (95% confidence interval: 1.61-2.30 years) 1-year and 2-year overall survival rates were 97% (95% confidence interval: 94-100%) and 95% (95% confidence interval: 91-99%), respectively. Age above 70 years was associated with a significantly shorter overall survival (P<0.001) compared to that of younger patients. So far no relapses have been observed. Six patients (4%) died in complete remission at a median of 0.95 years after diagnosis (range, 0.18-2.38 years). Our data confirm the efficiency and durability of arsenic trioxide and all-trans retinoic acid therapy in the primary management of adults with low-/intermediate-risk acute promyelocytic leukemia in the real-life setting, irrespective of age.


Asunto(s)
Trióxido de Arsénico , Leucemia Promielocítica Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Trióxido de Arsénico/uso terapéutico , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Persona de Mediana Edad , Estudios Prospectivos , Inducción de Remisión , Medición de Riesgo , Resultado del Tratamiento , Tretinoina/uso terapéutico , Adulto Joven
8.
Br J Haematol ; 167(4): 506-13, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25160558

RESUMEN

Bing-Neel syndrome (BNS), a rare neurological syndrome associated with Waldenström macroglobulinaemia (WM), is a direct involvement of the central nervous system by lymphoplasmacytoid cells characterized with an adverse prognostic. The MYD88 L265P mutation has been identified in the vast majority of patients with WM. The diagnosis of BNS is often challenging because of the variety of clinical presentations associated with difficult histological techniques. We hypothesized that identification of MYD88 L265P mutation in the cerebrospinal fluid (CSF) would contribute to the diagnosis of BNS in addition to imaging, flow cytometry and cytology. We identified MYD88 L265P mutation in the CSF and the bone marrow of all cases of BNS using quantitative polymerase chain reaction qPCR and Sanger sequencing. Copy neutral loss of heterozygosity including MYD88 was observed in one case. No mutation of CXCR4, CD79A and CD79B was observed in parallel. We further showed that monitoring the quantitative expression of MYD88 L265P mutation might be a useful molecular tool to monitor response to chemotherapy using qPCR. In conclusion, identification of MYD88 L265P mutation might be a new molecular-based biomarker tool to add to the diagnostic and monitoring armamentarium for BNS.


Asunto(s)
Heterocigoto , Mutación Missense , Factor 88 de Diferenciación Mieloide/genética , Proteínas de Neoplasias/genética , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/genética , Macroglobulinemia de Waldenström/genética , Adulto , Anciano , Médula Ósea/metabolismo , Médula Ósea/patología , Humanos , Masculino , Persona de Mediana Edad , Factor 88 de Diferenciación Mieloide/metabolismo , Proteínas de Neoplasias/metabolismo , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/patología , Estudios Prospectivos , Síndrome , Macroglobulinemia de Waldenström/líquido cefalorraquídeo , Macroglobulinemia de Waldenström/patología
9.
Bull Cancer ; 111(10): 980-986, 2024 Oct.
Artículo en Francés | MEDLINE | ID: mdl-39266427

RESUMEN

In response to the French hospital system crisis and the challenges faced by the heads of departments, we have undertaken an initiative to create a community of heads of haematology departments willing to assist each other. Our inaugural seminar, held in January 2023, established the foundational "core" group of heads of department. Throughout 2023, this emerging community has prospered, offering sustained support to peers. In January 2024, we broadened our community to include other heads of departments, following a second seminar gathering 36 participants. During this event, we took the time to exchange thoughts and reflect on our missions. Building on the experience of guest speakers and employing methods of co-development and co-construction in plenary sessions, small-group workshops, and social gathering, we were able to discover and experience the collective intelligence, creativity, strength, and support stemming from such a group. This peer community of heads of departments stands as a powerful tool for management support, whereby personal experiences nourish and enrich the experience of others. We hope that our initiative will inspire heads of departments from other specialties so that, together, we can better work towards our missions as heads of departments and collaborate on rebuilding the hospital "from the bottom up".


Asunto(s)
Hematología , Departamentos de Hospitales , Humanos , Francia , Hematología/organización & administración , Departamentos de Hospitales/organización & administración , Grupo Paritario
10.
EJHaem ; 4(3): 779-791, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37601853

RESUMEN

Primary myelofibrosis (PMF) and polycythaemia vera (PV) are rare BCR-ABL1-negative myeloproliferative neoplasms, associated with an increased risk of thrombosis, haemorrhagic complications and progression to fibrosis or leukaemia or fibrosis for PV. Both diseases are characterised by biological and clinical heterogeneity, leading to great variability in their management in routine clinical practice. In this review, we present an updated overview of the diagnosis, prognosis and treatment of PMF and PV, and we discuss how our multidisciplinary expert group based across France translates this evidence-based knowledge into routine clinical practice.

11.
Leukemia ; 37(1): 91-101, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36376378

RESUMEN

The real-world efficacy and safety of gilteritinib was assessed in an ambispective study that included 167 R/R FLT3-mutated AML patients. Among them, 140 received gilteritinib as single agent (cohort B), including 67 previously treated by intensive chemotherapy and midostaurin (cohort C). The main differences in patient characteristics in this study compared to the ADMIRAL trial were ECOG ≥ 2 (83.6% vs. 16.6%), FLT3-TKD mutation (21.0% vs. 8.5%), primary induction failure (15.0% vs. 40.0%) and line of treatment (beyond 2nd in 37.1% vs. 0.0%). The rates of composite complete remission, excluding those that occurred after hematopoietic stem cell transplantation (HSCT), were similar at respectively 25.4% and 27.5% in cohorts B and C. Median overall survival (OS) for these two groups was also similar at respectively 6.4 and 7.8 months. Multivariate analyses for prognostic factors associated with OS identified female gender (HR 1.61), adverse cytogenetic risk (HR 2.52), and allogenic HSCT after gilteritinib (HR 0.13). Although these patients were more heavily pretreated, these real-world data reproduce the results of ADMIRAL and provide new insights into the course of patients previously treated by intensive chemotherapy and midostaurin and beyond the 2nd line of treatment who can benefit from treatment in an outpatient setting.


Asunto(s)
Leucemia Mieloide Aguda , Humanos , Femenino , Mutación , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Estaurosporina/uso terapéutico , Tirosina Quinasa 3 Similar a fms/genética , Tirosina Quinasa 3 Similar a fms/uso terapéutico
13.
Eur J Haematol ; 88(4): 306-13, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22126676

RESUMEN

BACKGROUND: The Prognostic Inflammatory and Nutritional Index (PINI) is a simple scoring system that aggregates two blood markers of inflammatory [C-reactive protein (CRP) and orosomucoid] and of nutritional (albumin and prealbumin) states. It is used in routine practice in geriatric medicine, especially in hospitalized elderly patients. This study was undertaken to evaluate the usefulness of PINI index in multiple myeloma (MM), a malignancy of the elderly. METHOD: The PINI score was determined in 231 previously untreated patients with MM, of whom 112 were ≥65 yrs old. The serum albumin, prealbumin, orosomucoid (human α1-acid glycoprotein), and hsCRP are measured routinely by immunonephelometry. RESULTS: In the overall population and the elderly subset, PINI ≥ 4 ('high PINI') was correlated with a shorter median survival, 26 vs. 65 months in the high and low PINI groups, respectively. The prognostic impact of PINI index was dramatic in the elderly MM subgroup, 6 and 45 months, respectively. The high PINI index also predicted for shorter survival in various groups with good prognostic, such as low International Staging System (ISS) stages, low b2m, and absence of del17p and t(4;14), further demonstrating its prognostic impact on overall survival. In multivariate analysis, PINI index provided additional survival prognostic information to b2m in a b2m/PINI model. CONCLUSION: PINI index appears to be a useful and easy-to-perform marker in routine to determine the prognosis of patients with MM, especially in the elderly population. PINI might represent an alternative to ISS score, especially in elderly patients, in the future.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/metabolismo , Evaluación Nutricional , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento , Albúminas/metabolismo , Proteína C-Reactiva/biosíntesis , Hospitalización , Humanos , Inflamación , Persona de Mediana Edad , Mieloma Múltiple/sangre , Orosomucoide/biosíntesis , Prealbúmina/metabolismo , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
14.
Genes (Basel) ; 13(1)2022 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-35052472

RESUMEN

High oxygen affinity hemoglobin (HOAH) is the main cause of constitutional erythrocytosis. Mutations in the genes coding the alpha and beta globin chains (HBA1, HBA2 and HBB) strengthen the binding of oxygen to hemoglobin (Hb), bringing about tissue hypoxia and a secondary erythrocytosis. The diagnosis of HOAH is based upon the identification of a mutation in HBA1, HBA2 or HBB in specialized laboratories. Phenotypic studies of Hb are also useful, but electrophoretic analysis can be normal in 1/3 of cases. The establishment of the dissociation curve of Hb can be used as another screening test, a shift to the left indicating an increased affinity for Hb. The direct measurement of venous P50 using a Hemox Analyzer is of great importance, but due to specific analytic conditions, it is only available in a few specialized laboratories. Alternatively, an estimated measurement of the P50 can be obtained in most of the blood gas analyzers on venous blood. The aim of our study was therefore to determine whether a normal venous P50 value could rule out HOAH. We sequenced the HBB, HBA1 and HBA2 genes of 75 patients with idiopathic erythrocytosis. Patients had previously undergone an exhaustive medical check-up after which the venous P50 value was defined as normal. Surprisingly, sequencing detected HOAH in three patients (Hb Olympia in two patients, and Hb St Nazaire in another). A careful retrospective examination of their medical files revealed that (i) one of the P50 samples was arterial; (ii) there was some air in another sample; and (iii) the P50 measurement was not actually done in one of the patients. Our study shows that in real life conditions, due to pre-analytical contingencies, a venous P50 value that is classified as being normal may not be sufficient to rule out a diagnosis of HOAH. Therefore, we recommend the systematic sequencing of the HBB, HBA1 and HBA2 genes in the exploration of idiopathic erythrocytosis.


Asunto(s)
Hemoglobina Glucada/genética , Hemoglobina A2/genética , Hemoglobinas/genética , Mutación , Oxígeno/metabolismo , Policitemia/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Genotipo , Hemoglobina Glucada/análisis , Hemoglobina A2/análisis , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Policitemia/sangre , Policitemia/genética , Estudios Retrospectivos , Adulto Joven
15.
Leuk Res ; 118: 106871, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35633618

RESUMEN

Subsequent blast (BP) or accelerated phase (AP) is a severe complication of Philadelphia-negative myeloproliferative neoplasms (MPNs). The prognosis is generally dismal, but hypomethylating agents (HMAs) may induce a long-lasting response in a minority of patients. Here, we report a cohort of six patients with BP/AP-MPN who experienced MPN relapse after a leukemia response was obtained with azacytidine. Five of the patients achieved complete remission despite the presence of characteristics associated with poor prognosis, such as complex and monosomal karyotypes, TP53 mutations, and EVI1 overexpression. These remissions persisted for over five years in four of the 6 patients. All patients showed rapid reemergence of MPN within a median of two months with thrombocytosis requiring the addition of anagrelide, hydroxyurea, or ruxolitinib given continuously in parallel with the azacytidine cycle. Serial JAK2 V617F allelic burden measurements showed little variation. Thromboembolic events occurred in 3 patients, one leading to death. These findings confirm that HMA may reverse the disease course in AP/BP-MPN to a more chronic phase that may last for years but also lead to morbidity and mortality. Combining maintenance therapy with HMA and MPN-specific drugs appears to be a possible approach to avoiding leukemia relapse and controlling MPN disease.


Asunto(s)
Leucemia , Trastornos Mieloproliferativos , Neoplasias , Azacitidina/uso terapéutico , Humanos , Janus Quinasa 2/genética , Leucemia/tratamiento farmacológico , Activación de Linfocitos , Mutación , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/genética , Neoplasias/tratamiento farmacológico , Recurrencia
17.
Blood Adv ; 5(5): 1442-1451, 2021 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-33666653

RESUMEN

We aimed to study the prognostic impact of the mutational landscape in primary and secondary myelofibrosis. The study included 479 patients with myelofibrosis recruited from 24 French Intergroup of Myeloproliferative Neoplasms (FIM) centers. The molecular landscape was studied by high-throughput sequencing of 77 genes. A Bayesian network allowed the identification of genomic groups whose prognostic impact was studied in a multistate model considering transitions from the 3 conditions: myelofibrosis, acute leukemia, and death. Results were validated using an independent, previously published cohort (n = 276). Four genomic groups were identified: patients with TP53 mutation; patients with ≥1 mutation in EZH2, CBL, U2AF1, SRSF2, IDH1, IDH2, NRAS, or KRAS (high-risk group); patients with ASXL1-only mutation (ie, no associated mutation in TP53 or high-risk genes); and other patients. A multistate model found that both TP53 and high-risk groups were associated with leukemic transformation (hazard ratios [HRs] [95% confidence interval], 8.68 [3.32-22.73] and 3.24 [1.58-6.64], respectively) and death from myelofibrosis (HRs, 3.03 [1.66-5.56] and 1.77 [1.18-2.67], respectively). ASXL1-only mutations had no prognostic value that was confirmed in the validation cohort. However, ASXL1 mutations conferred a worse prognosis when associated with a mutation in TP53 or high-risk genes. This study provides a new definition of adverse mutations in myelofibrosis with the addition of TP53, CBL, NRAS, KRAS, and U2AF1 to previously described genes. Furthermore, our results argue that ASXL1 mutations alone cannot be considered detrimental.


Asunto(s)
Mielofibrosis Primaria , Teorema de Bayes , Genómica , Humanos , Mutación , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/genética , Pronóstico , Proteínas Represoras/genética
18.
Clin Lymphoma Myeloma ; 9(1): 71-3, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19362978

RESUMEN

Nucleoside Analogues (NA) are considered as appropriate agents in the treatment of Waldenström's Macroglobulinemia (WM). There are sporadic reports on increased incidence of transformation to high grade non-Hodgkin lymphoma (transformation to NHL) and development of therapy related-myelodysplasia/acute leukemia (t-MDS/AML) among WM patients treated with NA. Several studies have been conducted in Europe and in the United States to retrospectively examine the incidence of such events in WM patients. The incidences of transformation to NHL and t-MDS/AML ranged from 4.7% to 8%, and from 1.4% to 8.9%, respectively, and demonstrated an increased incidence of these late events among WM patients treated with NA. The effect of these secondary malignancies needs to be better evaluated in prospective studies, especially in young patients. These NA treatment-associated risks should not by themselves be used to justify avoidance of NA therapy for WM patients but should be used in considering risk versus benefit for a particular patient given the expanding options of therapy for WM patients.


Asunto(s)
Nucleósidos/uso terapéutico , Macroglobulinemia de Waldenström/tratamiento farmacológico , Progresión de la Enfermedad , Humanos , Leucemia Mieloide Aguda/patología , Linfoma no Hodgkin/patología , Nucleósidos/efectos adversos , Macroglobulinemia de Waldenström/patología
19.
Mol Cytogenet ; 10: 26, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28680482

RESUMEN

BACKGROUND: Our aim was to set the FISH combination of del(17p13), t(4;14), 1q21 gain and del(1p32), four adverse cytogenetic factors rarely evaluated together, and compare our technical thresholds with those defined in the literature. METHODS: Two hundred thirty-three patients with MM at diagnosis were studied using FISH to target 4 unfavorable cytogenetic abnormalities: 17p13 deletion, t(4;14) translocation, 1p32 deletion and 1q21 gain. Technical thresholds were determined for each probe using isolated CD138-expressing PC from patients without MM. RESULTS: The FISH analysis identified abnormalities in 79.0% of patients. Del(17p13) was detected in 15.0% of cases, t(4;14) in 11.5%, 1q21 gain in 37.8% and del(1p32) in 8.7%. Adding 1p32/1q21 FISH probes has enabled us to identify adverse cytogenetic profiles in 39.0% of patients without del(17p13) or t(4;14). Clonal heterogeneity was observed in 51.1% of patients as well as an increase in the number of adverse abnormalities when related clones were greater than or equal to 2 (85.1% against 45.6%). CONCLUSION: FISH allowed detecting accumulation of adverse abnormalities and clonal heterogeneity in MM with a combination of 4 probes. The impacts of these two parameters need to be evaluated, and could be included in future cytogenetic classifications.

20.
Clin Cancer Res ; 20(12): 3254-60, 2014 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-24714772

RESUMEN

PURPOSE: Solitary plasmacytoma (SP) is a localized proliferation of monoclonal plasma cells in either bone or soft tissue, without evidence of multiple myeloma (MM), and whose prognosis is marked by a high risk of transformation to MM. EXPERIMENTAL DESIGN: We studied the impact of FDG-PET/CT (2[18F]fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography) on the risk of transformation of SP to overt MM among other markers in a series of 43 patients diagnosed with SP. RESULTS: Median age was 57.5 years; 48% of patients had an abnormal involved serum-free light chain (sFLC) value, and 64% had an abnormal sFLC ratio at diagnosis. Thirty-three percent had two or more hypermetabolic lesions on initial PET/CT, and 20% had two or more focal lesions on initial MRI. With a median follow-up of 50 months, 14 patients transformed to MM with a median time (TTMM) of 71 months. The risk factors that significantly shortened TTMM at diagnosis were two or more hypermetabolic lesions on PET/CT, abnormal sFLC ratio and involved sFLC, and to a lesser extent at completion of treatment, absence of normalized involved sFLC and PET/CT or MRI. In a multivariate analysis, abnormal initial involved sFLC [OR = 10; 95% confidence interval (CI), 1-87; P = 0.008] and PET/CT (OR = 5; 95% CI, 0-9; P = 0.032) independently shortened TTMM. CONCLUSIONS: An abnormal involved sFLC value and the presence of at least two hypermetabolic lesions on PET/CT at diagnosis of SP were the two predictors of early evolution to myeloma in our series. This data analysis will need confirmation in a larger study, and the study of these two risk factors may lead to a different management of patients with SP in the future. .


Asunto(s)
Neoplasias Óseas/patología , Transformación Celular Neoplásica/patología , Fluorodesoxiglucosa F18 , Cadenas Ligeras de Inmunoglobulina/metabolismo , Mieloma Múltiple/patología , Plasmacitoma/patología , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Biomarcadores de Tumor/análisis , Neoplasias Óseas/metabolismo , Neoplasias Óseas/mortalidad , Transformación Celular Neoplásica/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Mieloma Múltiple/mortalidad , Estadificación de Neoplasias , Plasmacitoma/metabolismo , Plasmacitoma/mortalidad , Pronóstico , Radiofármacos , Estudios Retrospectivos , Tasa de Supervivencia
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