RESUMEN
ABSTRACT: Histologic transformation of Waldenström macroglobulinemia (HT-WM) carries a poor prognosis with standard treatments. Here, we report the first series of HT-WM treated with chimeric antigen receptor T cells showing a high efficacy and no unexpected toxicity.
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Antígenos CD19 , Inmunoterapia Adoptiva , Macroglobulinemia de Waldenström , Humanos , Macroglobulinemia de Waldenström/terapia , Macroglobulinemia de Waldenström/inmunología , Macroglobulinemia de Waldenström/patología , Masculino , Anciano , Inmunoterapia Adoptiva/métodos , Femenino , Antígenos CD19/inmunología , Persona de Mediana Edad , Receptores Quiméricos de Antígenos/inmunología , Linfocitos T/inmunología , Linfocitos T/patología , Resultado del TratamientoRESUMEN
Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n = 749) or at the end (n = 635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT: 5.7% vs 5.8%, P = .98; 3-year difference: 0.04% (-2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n = 1253). In patients with a high CNS international prognostic index (n = 600), the 3-year CNS relapse rate was 9.1%, with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with a reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX vs EOT, with 308 of 1573 (19.6%) i-HD-MTX treatments resulting in a delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk vs i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion.
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Neoplasias del Sistema Nervioso Central , Linfoma de Células B Grandes Difuso , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/prevención & control , Ciclofosfamida , Doxorrubicina , Humanos , Linfoma de Células B Grandes Difuso/patología , Metotrexato , Recurrencia Local de Neoplasia/tratamiento farmacológico , Prednisona , Estudios Retrospectivos , Rituximab/uso terapéutico , VincristinaRESUMEN
Registries constitute an interesting source of real-world data and bring complementary information to randomised controlled trials. They are of particular importance in rare diseases such as Waldenström macroglobulinaemia (WM), which can present with various clinical and biological features. In their paper Uppal and colleagues describe the development of the Rory Morrison Registry, the UK registry for WM and IgM-related disorders and highlight the profound changes in therapies both at first-line and relapsed settings in the recent years. Commentary on: Uppal E. et al. The WMUK Rory Morrison Registry for Waldenström Macroglobulinaemia: the growth of a national registry for a rare disorder. Br J Haematol. 2023;201:905-912.
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Macroglobulinemia de Waldenström , Humanos , Macroglobulinemia de Waldenström/tratamiento farmacológico , Sistema de Registros , Reino Unido/epidemiologíaRESUMEN
PURPOSE OF REVIEW: The discovery of recurring somatic mutations, in particular MYD88 and CXCR4 mutations, in Waldenström macroglobulinemia (WM), a rare B-cell lymphoproliferative disorder, led in the last decade to the development of several therapeutic agents with high efficacy. This review aims to provide an overview of available treatments in WM and novel agents, focusing on studies published over recent years. RECENT FINDINGS: There is no international consensus on the best first-line option in treatment-naïve patients. Randomized clinical trials are rare in WM and there has been no prospective comparison of chemoimmunotherapy and BTK inhibitors in the frontline setting. Chemoimmunotherapy and BTK inhibitors, the two feasible and most widely used treatments in first-line treatment, represent very different options in terms of duration of therapy, route of administration, cost, and adverse effect. In addition to tumor genotype and patient comorbidities, choice of therapy in WM should take into account these parameters. Results of ongoing and future clinical trials evaluating fixed-duration combinations with BTK inhibitors and novel agents are awaited.
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Macroglobulinemia de Waldenström , Humanos , Macroglobulinemia de Waldenström/tratamiento farmacológico , Macroglobulinemia de Waldenström/genética , Macroglobulinemia de Waldenström/patología , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/farmacología , Recurrencia Local de Neoplasia , Transducción de Señal , MutaciónRESUMEN
In symptomatic Waldenström macroglobulinemia (sWM) patients, prognosis is assessed with the international prognostic scoring system (IPSSWM). In follicular lymphoma and other B-cell and T-cell lymphomas, disease progression within 24 months (POD24) or (in patients without POD24) after 24 months has been proposed as the start date for stratifying subsequent survival. In the present report, we assessed in a large series of 472 sWM patients, the prognostic value of this new dynamic endpoint already reported in many other lymphomas subtypes. The 3 year subsequent survival for patients with POD24 was 75% and 93% for patients without POD24. In sWM patients, departure from the proportional hazards assumption complicated this analysis. In patients without POD24, the median subsequent progression-free survival time of 43 months accounted for favorable outcome, whereas survival after progression was not influenced by the time to progression. In addition, sensitivity analysis showed that the baseline IPSSWM score also influenced survival after POD24. In sWM patients, we conclude that the apparent difference in survival after POD24 or the 24 months time-point (in patients without POD24) is mainly explained by the prolonged subsequent progression free survival of latter patients. Indeed, the mortality after progression is not influenced by the time to this event.
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Progresión de la Enfermedad , Macroglobulinemia de Waldenström , Humanos , Pronóstico , Supervivencia sin Progresión , Macroglobulinemia de Waldenström/patología , Macroglobulinemia de Waldenström/terapiaRESUMEN
Aggressive primary cutaneous T-cell lymphomas include advanced-stage mycosis fungoides (stage ≥ IIB mycosis fungoides), Sézary syndrome, gamma/delta cutaneous lymphoma, nasal type lymphoma, aggressive epidermotropic CD8+ T-cell lymphoma and some cutaneous lymphomas not otherwise specified. To evaluate their long-term prognosis, we conducted a retrospective cohort study of 85 patients diagnosed between 2005 and 2020 with advanced-stage mycosis fungoides (n = 48), Sézary syndrome (n = 28) or aggressive non-mycosis fungoides/Sézary syndrome subtypes (n = 9). The median survival times in these 3 groups were 118.7, 45.7 and 11.2 months, respectively, and the 5-year survival rates were 55.3%, 27.8% and 33.3%, respectively. Multivariate analyses in patients with mycosis fungoides/Sézary syndrome identified age ≥ 70 years, Eastern Cooperative Oncology Group Performance Status ≥ 2, and the high-risk group according to the Cutaneous Lymphoma International Consortium prognostic model, as adverse prognostic factors. Seven patients in this mycosis fungoides/ Sézary syndrome group were in complete long-term remission after treatment with bexarotene, including 4 patients living without any treatment for 16-101 months.
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Linfoma Cutáneo de Células T , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Anciano , Humanos , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/tratamiento farmacológico , Micosis Fungoide/diagnóstico , Micosis Fungoide/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/tratamiento farmacológico , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
Histological transformation into diffuse large B-cell lymphoma is a rare complication in patients with Waldenström macroglobulinemia (WM) usually associated with a poor prognosis. The objective of this study was to develop and validate a prognostic index for survival in transformed WM patients. Through this multicenter, international collaborative effort, we developed a scoring system based on data from 133 patients with transformed WM who were evaluated between 1995 and 2016 (training cohort). Univariate and multivariate analyses were used to propose a prognostic index with 2-year survival after transformation as an end-point. For external validation, a data set of 67 patients was used to evaluate the performance of the model (validation cohort). By multivariate analysis, three adverse covariates were identified as independent predictors of 2-year survival after transformation: elevated serum LDH (2 points), platelet count < 100 x 109/L (1 point) and any previous treatment for WM (1 point). Three risk groups were defined: low-risk (0-1 point, 24% of patients), intermediate-risk (2-3 points, 59%, hazard ratio (HR) = 3.4) and high-risk (4 points, 17%, HR = 7.5). Two-year survival rates were 81%, 47%, and 21%, respectively (P < 0.0001). This model appeared to be a better discriminant than the International Prognostic Index (IPI) and the revised IPI (R-IPI). We validated this model in an independent cohort. This easy-to-compute scoring index is a robust tool that may allow identification of groups of transformed WM patients with different outcomes and could be used for improving the development of risk-adapted treatment strategies.
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Linfoma de Células B Grandes Difuso , Macroglobulinemia de Waldenström , Humanos , Pronóstico , Modelos de Riesgos Proporcionales , Tasa de Supervivencia , Macroglobulinemia de Waldenström/diagnósticoRESUMEN
Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma. The prevalence of hypercalcemia in this neoplasm and its prognostic significance is unclear. We retrospectively evaluated the prevalence of hypercalcemia at diagnosis of DLBCL and explored associations of hypercalcemia with clinical factors and outcome. Outcome was assessed using event-free survival at 24 months (EFS24). A total of 305 patients (248 de novo DLBCL and 57 transformed indolent lymphomas) diagnosed between 2006 and 2018 in Reims were analyzed. The prevalence of calcemia >10.5 mg/dL at diagnosis of de novo DLBCL and transformed indolent lymphomas was 23% and 26%, respectively. Hypercalcemia in de novo DLBCL was strongly associated with high-risk features, especially with International Prognostic Index (IPI) components, but also with B symptoms, ß2-microglobulin, hemoglobin, and albumin levels. The diagnosis-to-treatment interval was significantly shorter for hypercalcemic patients (P = .001). These associations with adverse prognostic factors translated into lower rates of EFS24 (HR = 1.66; 95% CI, 1.08-2.54) and shorter PFS (P = .0059) and OS (P = .0003) for patients with lymphoma-related hypercalcemia but not independently of IPI parameters. These data suggest that hypercalcemia is rather a biomarker of the underlying biological aggressiveness of DLBCL.
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Hipercalcemia/epidemiología , Hipercalcemia/mortalidad , Linfoma de Células B Grandes Difuso/diagnóstico , Tiempo de Tratamiento/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Hipercalcemia/terapia , Linfoma de Células B Grandes Difuso/complicaciones , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
Histological transformation in Waldenström macroglobulinemia (WM) is an uncommon complication, with limited data, particularly regarding the impact of MYD88 L265P mutation on transformation. We examined risk factors and outcomes associated with transformation in WM, highlighting the role of MYD88 L265P mutation. Patients with WM seen at Mayo Clinic, Rochester, USA and University Hospital of Reims, France, between 01/01/1996 and December 31, 2017 were included; 50 (4.3%) of 1147 patients transformed to a high-grade lymphoma, with median time-to-transformation of 4.5 (range 0-21) years in the transformed cohort. The MYD88 L265P mutation status was known in 435/1147 (38%) patients (406 with non-transformed WM and 29 patients in transformed cohort). On multivariate analysis, MYD88 WT status alone was an independent predictor of transformation (odds ratio, 7[95%CI: 2.1-23]; P = .003). Additionally, the MYD88 WT status was independently associated with shorter time-to-transformation (HR 7.9 [95%CI: 2.3-27; P = .001]), with a 5-year transformation rate of 16% for MYD88 WT vs 2.8% with MYD88 L265P mutated patients. Patients with transformation demonstrated a significant increase in risk of death compared to patients who did not transform (HR 5.075; 95%CI: 3.8-6.8; P < .001). In conclusion, the MYD88 WT status is an independent predictor of transformation and associated with a shorter time-to-transformation. Additionally, transformation conferred an inferior overall survival in patients with WM.
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Transformación Celular Neoplásica/genética , Linfoma , Mutación Missense , Factor 88 de Diferenciación Mieloide/genética , Proteínas de Neoplasias/genética , Macroglobulinemia de Waldenström , Adulto , Anciano , Anciano de 80 o más Años , Sustitución de Aminoácidos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Linfoma/genética , Linfoma/mortalidad , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Factores de Tiempo , Macroglobulinemia de Waldenström/genética , Macroglobulinemia de Waldenström/mortalidadRESUMEN
Cutaneous involvement in Waldenström's macroglobulinaemia (WM) has been poorly characterized. To describe this involvement, a retrospective study of 19 patients with WM and cutaneous involvement of tumour B cells was performed. Twelve patients (group 1) had lymphoplasmacytic, non-transformed cutaneous proliferation, while in 7 cases (group 2) cutaneous involvement corresponded to histological transformation. In group 1, skin involvement was inaugural in 6 cases. The lesions were infiltrated plaques (83%), papules (25%) and tumours (42%). Four patients had a similar clinical picture (purplish, bilateral and symmetrical infiltration on the face). MYD88 L265P mutation was detected in the skin biopsy in all 6 cases tested. The 3-year specific survival rate was 88%. In group 2, cutaneous transformation occurred during the follow-up of the WM (71%). Lesions presented as ulcerated tumours (86%) of the trunk (57%) and lower limbs (57%). The 3-year specific survival rate was 22%. Skin involvement in WM has distinctive characteristics (e.g. clinical, histological, immunohistochemical, MYD88 L265P mutation).
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Macroglobulinemia de Waldenström , Humanos , Mutación , Factor 88 de Diferenciación Mieloide/genética , Estudios Retrospectivos , Piel , Macroglobulinemia de Waldenström/diagnóstico , Macroglobulinemia de Waldenström/genéticaAsunto(s)
Neoplasias del Sistema Nervioso Central , Linfoma de Células B Grandes Difuso , Humanos , Metotrexato , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/prevención & control , Rituximab/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/prevención & control , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Vincristina , Ciclofosfamida , DoxorrubicinaRESUMEN
Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p- and the additional aberrations influenced the prognosis in a series of 195 patients with 17p-CLL. Loss of 17p resulted primarily from an unbalanced translocation (70%) with several chromosome partners (the most frequent being chromosome 18q), followed by deletion 17p (23%), monosomy 17 (8%), isochromosome 17q [i(17q)] (5%) and a ring chromosome 17 (2%). In a univariate analysis, monosomy 17, a highly complex karyotype (≥5 abnormalities), and 8q24 gain were associated with poor treatment-free survival, and i(17q) (P = .04), unbalanced translocations (P = .03) and 8q24 gain (P = .001) were significantly associated with poor overall survival. In a multivariate analysis, 8q24 gain remained a significant predictor of poor overall survival. We conclude that 17p deletion and 8q24 gain have a synergistic impact on outcome, and so patients with this "double-hit" CLL have a particularly poor prognosis. Systematic, targeting screening for 8q24 gain should therefore be considered in cases of 17p- CLL.
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Deleción Cromosómica , Cromosomas Humanos Par 17/ultraestructura , Cromosomas Humanos Par 8/ultraestructura , Leucemia Linfocítica Crónica de Células B/genética , Translocación Genética , Trisomía , Cariotipo Anormal , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Genes p53 , Humanos , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Leucemia Linfocítica Crónica de Células B/mortalidad , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genética , Pronóstico , Estudios RetrospectivosRESUMEN
Carmustine shortage has led to an increase use of alternative conditioning regimens prior to autologous stem cell transplantation for the treatment of lymphoma, including Bendamustine-based (BeEAM). The aim of this study was to evaluate the safety of the BeEAM regimen in a large cohort of patients. A total of 474 patients with a median age of 56 years were analyzed. The majority of patients had diffuse large B-cell lymphoma (43.5%). Bendamustine was administered at a median dose of 197 mg/m2 /day (50-250) on days-7 and -6. The observed grade 1-4 toxicities included mucositis (83.5%), gastroenteritis (53%), skin toxicity (34%), colitis (29%), liver toxicity (19%), pneumonitis (5%), and cardiac rhythm disorders (4%). Nonrelapse mortality (NRM) was reported in 3.3% of patients. Acute renal failure (ARF) was reported in 132 cases (27.9%) (G ≥2; 12.3%). Organ toxicities and death were more frequent in patients with post conditioning renal failure. In a multivariate analysis, pretransplant chronic renal failure, bendamustine dose >160 mg/m2 and age were independent prognostic factors for ARF. Pretransplant chronic renal failure, hyperhydration volume, duration of hyperhydration, and etoposide dose were predictive factors of NRM. A simple, four-point scoring system can stratify patients by levels of risk for ARF and may allow for a reduction in the bendamustine dose to avoid toxicity. Drugs shortage may have dangerous consequences. Prospective, comparative studies are needed to confirm the toxicity/efficacy extents from this conditioning regimen compared to other types of high dose therapy.
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Clorhidrato de Bendamustina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma/terapia , Acondicionamiento Pretrasplante/métodos , Lesión Renal Aguda/etiología , Adulto , Anciano , Clorhidrato de Bendamustina/administración & dosificación , Clorhidrato de Bendamustina/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Trasplante AutólogoRESUMEN
Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a rare and poorly reported complication of Waldenström macroglobulinaemia (WM). We performed a retrospective study of 77 WM patients with biopsy-proven transformation to DLBCL. The median time from WM diagnosis to HT was 4·6 years and 16 patients (21%) had never been treated for WM. At HT, extranodal sites were observed in 91% of patients with a rather high incidence of central nervous system, cutaneous or testicular involvement. Fluorodeoxyglucose-positron emission tomography was performed in half of the patients and the median maximum standardized uptake value was 15 for transformed disease. More than 80% of cases with available data for assessment by the Hans' algorithm harboured a non-germinal centre B-cell phenotype. First-line treatment for transformation consisted of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-like regimen in 85% of patients. The overall response rate after first-line treatment was 61% and the median overall survival was only 16 months for the entire cohort. Time to transformation above 5 years (P = 0·0004) and elevated LDH (P = 0·02) were associated with worse outcome. Based on these findings, HT should be considered and lead to a biopsy in WM patients presenting with extranodal involvement, elevated LDH and constitutional symptoms. The optimal therapeutic approaches remain to be defined.
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Transformación Celular Neoplásica/patología , Linfoma de Células B Grandes Difuso/patología , Macroglobulinemia de Waldenström/patología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Biopsia , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Fluorodesoxiglucosa F18 , Humanos , L-Lactato Deshidrogenasa/sangre , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones/métodos , Prednisona/uso terapéutico , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Rituximab , Análisis de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Vincristina/uso terapéutico , Macroglobulinemia de Waldenström/diagnóstico por imagenRESUMEN
Ultra high-risk chronic lymphocytic leukemia (CLL) and Richter's syndrome (RS) usually display a poor prognosis. Platinum and cytarabine-based regimens have not been evaluated in large cohorts of patients with CLL or RS. This retrospective study was aimed to assess the efficacy of these regimens in 75 patients with relapsed/refractory (R/R) CLL or RS. Forty-seven patients had R/R CLL (including 36 ultra high-risk CLL) and 28 had RS. Median age was 62 years (range, 18-79 years). Median number of previous therapies was 3 (range, 1-7), including fludarabine-based regimens (75%) and alemtuzumab (32%), and 61% of patients were refractory to their last treatment. Deletions of chromosomes 17p and 11q were found in 40% and 39% of cases, respectively. The overall response rates were 60% with 24% complete response (CR) in CLL, and 43% with 25% CR in RS. The median progression-free survival and overall survival were 11 and 14.6 months, respectively. Fludarabine refractoriness and 17p deletion were not associated with a poorer outcome. The only factors predicting shorter survival were performance status ≥ 2 (P = 0.04) and albumin level <3.5 g/dL (P = 0.0004). Toxicities were mainly myelosuppression and infectious complications. Platinum and high-dose cytarabine-based regimens provide high response rates in high-risk CLL and in RS. However, these results will be challenged by the new arriving agents at least in non-transformed CLL.
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Antineoplásicos/administración & dosificación , Citarabina/administración & dosificación , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Compuestos Organoplatinos/administración & dosificación , Adolescente , Adulto , Anciano , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenAsunto(s)
Enfermedades Autoinmunes , Enfermedades Hematológicas , Leucemia Linfocítica Crónica de Células B , Purinas/administración & dosificación , Pirazoles/administración & dosificación , Pirimidinas/administración & dosificación , Quinazolinonas/administración & dosificación , Adenina/análogos & derivados , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/mortalidad , Supervivencia sin Enfermedad , Femenino , Enfermedades Hematológicas/tratamiento farmacológico , Enfermedades Hematológicas/mortalidad , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Piperidinas , Tasa de SupervivenciaRESUMEN
BACKGROUND: Besides International Prognostic Index (IPI) score, baseline prognostic factors of post-transplant lymphoproliferative disorders (PTLD) are poorly identified due to the rarity of the disease. New indexes derived from healthy organ uptake in baseline 18F-FDG PET/CT have been studied in immunocompetent lymphoma patients. The aim of this study is to evaluate the performances of the cerebellum-to-liver uptake ratio (denoted as CLIP) as a prognostic factor for PFS and OS. This retrospective multicenter study is based on patients with PTLD included in the K-VIROGREF cohort. The previously published threshold of 3.24 was used for CLIP in these analyses. RESULTS: A total of 97 patients was included with a majority of monomorphic diffuse large B-cell lymphoma subtype (78.3%). Both IPI score (≥ 3) and CLIP (< 3.24) were significant risk factors of PFS with corresponding hazard ratios of 2.0 (1.0-4.0) and 2.4 (1.3-4.5) respectively. For OS, CLIP was not significant and resulted in a hazard ratio of 2.6 (p = 0.059). Neither IPI score or Total Metabolic Tumor Volume reached significance for OS. CONCLUSION: CLIP is a promising predictor of PFS and perhaps OS in PTLD. Further prospective studies are needed to confirm these results.
RESUMEN
PURPOSE: Patients with Waldenström macroglobulinemia (WM) have disparate outcomes. Newer therapies have emerged since the development of International Prognostic Scoring System, and MYD88L265P mutation is now frequently assessed at diagnosis, warranting reexamination of the prognostic parameters. PATIENTS AND METHODS: We reviewed records of 889 treatment-naïve patients with active WM, consecutively seen between January 01, 1996, and December 31, 2017, to identify clinical predictors of overall survival (OS) in univariate analyses. Patients with complete data for the parameters significant on the univariate analyses (n = 341) were included in a multivariable analysis to derive a prognostic model, subsequently validated in a multi-institutional cohort. RESULTS: In the derivation cohort (n = 341), age (hazard ratio [HR], 1.9 [95% CI, 1.2 to 2.1]; P = .0009), serum lactate dehydrogenase (LDH) above upper limit of normal (HR, 2.3 [95% CI, 1.3 to 4.5]; P = .007), and serum albumin <3.5 g/dL (HR, 1.5 [95% CI, 0.99 to 2.3]; P = .056) were independently prognostic. By assigning a score of 1 point each to albumin <3.5 g/dL (HR, 1.5) and age 66-75 years (HR 1.4) and 2 points for age >75 years (HR, 2.6) or elevated LDH (HR, 2.3), four groups with distinct outcomes were observed on the basis of the composite scores. Five-year OS was 93% for the low-risk (score 0), 82% for low-intermediate risk (score 1), 69% for intermediate-risk (score 2), and 55% for the high-risk (score ≥3; P < .0001) groups. In the validation cohort (N = 335), the model maintained its prognostic value, with a 5-year OS of 93%, 90%, 75%, and 57% for the four groups, respectively (P < .0001). CONCLUSION: Modified Staging System for WM (MSS-WM), utilizing age, albumin, and LDH is a simple, clinically useful, and externally validated prognostic model that reliably risk-stratifies patients with symptomatic WM into four groups with distinct prognosis.