Inmunoterapia en hematología

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Advances in the treatment of malignant haemopathies

Abstract not availabl

Transplante de progenitores hematopoyéticos (TPH) alogénico no mieloablativo

El objetivo de este trabajo es investigar la toxicidad y demostrar la factibilidad y eficacia del injerto hematopoyético proveniente de un donante emparentado HLA-idéntico tras un acondicionamiento no mieloablativo en pacientes con enfermedades hematológicas de alto riesgo. Incluye 37 pacientes a los que se les realizó un TPH de sangre periférica procedente de un hermano HLA-idéntico. La mediana de células mononucleadas, CD3+ y CD34+ infundidas fue de 4,7 (1–9,7) x 108/Kg, 5,8 (1–36,3) x 107/Kg y 3,1 (1,3–9) x 106/Kg, respectivamente. La recuperación de neutrófilos se produjo en 17 días tras la infusión (7-39) y de plaquetas en 15 días (9-96). En la mayoría de pacientes se detectó un quimerismo mixto que pasó a completo a los 3 meses del trasplante; 9 pacientes precisaron la infusión de linfocitos del donante. Presentaron EICH aguda 16 pacientes (42%) (7 de ellos grados III-IV), 2 desarrollaron enfermedad venoclusiva hepática y 9 EICH crónica. Tras una mediana de seguimiento de 20 meses, 14 pacientes (38%) siguen vivos; 23 han fallecido (62%), 9 (24%) por progresión, 6 (16%) por EICH aguda y 8 (22%) por otras complicaciones. La supervivencia global actuarial a 2 años es del 32% (16-49 meses) y la supervivencia libre de progresión del 60% (43-77 meses). Se demuestra que la combinación de un acondicionamiento no mieloablativo con citostáticos y drogas inmunosupresoras produce una toxicidad moderada y permite el injerto con quimerismo total, en pacientes no candidatos a trasplante convencional por enfermedad de alto riesgo y presencia de comorbilidades asociadas.The aim of this paper is to investigate the toxicity and demonstrate the feasibility and efficacy of hematopoietic graft from an HLA-identical related donor after non-myeloablative conditioning in patients with high-risk hematological diseases. Includes 37 patients who underwent a peripheral blood HSCT from HLA-identical sibling. The median of infused mononuclear cells, CD 3 + cells and CD 34 + cells, was 4.7 (1-9.7) x 108/Kg, 5,8 (1-36.3) x 107/Kg and 3.1 (1 .3-9) x 106/Kg, respectively. Neutrophil recovery occurred at 17 days postinfusion (7-9) and platelets at 15 post-infusion. In most patients detected a mixed chimerism became a full three months after transplantation, nine patients required donor lymphocyte infusion. The majority of which became fully mixed at 3 months after transplantation, 9 patients required the infusion of donor lymphocytes. Sixteen patients presented acute GVHD (42%) (7 of them grade III-IV), 2 developed hepatic veno-occlusive disease and 9 chronic GVHD. After a median follow up of 20 months, 14 patients (38%) are alive, 23 have died (62%), 9 (24%) for progression, 6 (16%) for acute GVHD and 8 (22%) for further complications. Overall survival actuarial 2 years is 32% (16-49 months) and progression-free survival of 60% (43-77 months). It is shown that the combination of a non-myeloablative conditioning with cytostatic and immunosuppressive drugs produces a moderate toxicity and allows the graft with total chimerism in patients not candidates for conventional transplantation high-risk disease and presence of comorbidities

Un nuevo anticuerpo monoclonal

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RT-PCR multiplex para la detección simultánea de las mutaciones FLT3-ITD/NPM-1/AML1-ETO asociadas a Leucemia Mieloide Aguda

La Leucemia Mieloide Aguda (LMA) representa un grupo de neoplasias muy heterogéneo. Las aberraciones citogenéticas detectadas en el momento del diagnóstico son el marcador pronóstico más comúnmente utilizado. Sin embargo, el 20% de los casos de LMA presentan un cariotipo normal. Dentro de este grupo de pacientes la presencia de mutaciones del tipo FLT3-ITD se considera de mal pronóstico. Sin embargo, la presencia de la mutación NMP1 o AML1-ETO se asocia a un mejor pronóstico. En este contexto, el objetivo de este trabajo es el desarrollo de una técnica de diagnóstico molecular hematológico, que permita la detección simultánea de mutaciones para estos tres genes. Hemos desarrollado un método basado en la reacción en cadena de la polimerasa (PCR) que permite amplificar y visualizar simultáneamente estos 3 marcadores tanto desde ARN (un paso) como desde ADNc (dos pasos). De las 28 muestras analizadas, 6 (21,42 %) muestras fueron positivas para FLT3-ITD, 7 para NPM-1 (25%) y otras 4 (14,28) para AML1-ETO. Al comparar ambos métodos (ADNc vs ARN) con métodos convencionales los resultados de las 28 muestras estudiadas fue equivalente en el 100% de los casos, demostrando la robustez de los mismos.Acute Myeloid Leukemia (AML) is a heterogeneous group of neoplasms. The cytogenetic aberrations detected at the time of diagnosis are most commonly used as prognostic marker. However, 20% of AML patients exhibit a normal karyotype. Within this group of patients the presence of FLT3 -ITD mutations type is considered of poor prognosis. However, the presence of AML1 –ETO or NMP-1 or mutation is associated with a better prognosis. In this context, the aim of this work is to develop a technique of molecular diagnostic in hematology, allowing the simultaneous detection of mutations for these three genes. We have developed a method based on PCR that simultaneously amplifies and visualizes these three molecular markers both from RNA (one- step) and from cDNA (step two). Of the 28 samples tested, 6 (21.42%) samples were positive for FLT3 -ITD, 7 for NPM- 1 (25% ) and 4 ( 14,28 ) for AML1 -ETO . When comparing the two methods (cDNA vs RNA) by conventional techniques the obtained results from the 28 samples tested was equivalent in 100% of cases, demonstrating the robustness of this development

Outcome of Antifungal Combination Therapy for Invasive Mold Infections in Hematological Patients is Independent of the Chosen Combination

Invasive mold infection (IMI) remains a major cause of mortality in high-risk hematological patients. The aim of this multicenter retrospective, observational study was to evaluate antifungal combination therapy (ACT) for proven and probable IMI in hematological patients. We analyzed 61 consecutive cases of proven (n=25) and probable (n=36) IMI treated with ACT collected from eight Spanish hospitals from January 2005 to December 2009. Causal pathogens were: Aspergillus spp (n=49), Zygomycetes (n=6), Fusarium spp (n=3), and Scedosporium spp (n=3). Patients were classified in three groups according to the antifungal combination employed: Group A, liposomal amphotericin B (L-AmB) plus caspofungin (n=20); Group B, LAmB plus a triazole (n=20), and Group C, voriconazole plus a candin (n=21). ACT was well tolerated with minimal adverse effects. Thirty-eight patients (62%) achieved a favorable response (35 complete). End of treatment and 12-week survival rates were 62% and 57% respectively, without statistical differences among groups. Granulocyte recovery was significantly related to favorable response and survival (p<0.001) in multivariate analysis. Our results suggest that comparable outcomes can be achieved with ACT in high risk hematological patients with proven or probable IMI, whatever the combination of antifungal agents used

Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe

Alteraciones hematológicas y COVID-19

This work analyses haematological alterations in patients with SARS-CoV-2 infection. Patients with COVID-19 generally have respiratory pathology. Many patients with severe COVID-19 infection develop thromboembolic complications related to coagulopathy, which are associated with respiratory deterioration and death. Hemostatic studies in these patients may be confused with other alterations, which are seen on a regular basis in disseminated intravascular coagulation, sepsis or thrombotic microangiopathy. However, both the clinical and the laboratory data are different from those presented by this disease. Severe COVID-19 infection appears to cause a profound alteration of the coagulation system with inflammatory changes combined with endothelial lesions, with the release of Von Willebrand factor and plasminogen activators. This coagulopathy contributes to microvascular thrombosis, fibrin deposition and thromboembolic complications.All this has highlighted the need to use anticoagulant treatments, usually low molecular weight heparins, in prophylactic or therapeutic doses.On the other hand, the use of convalescent donor plasma for the treatment of this disease is discussed, as well as the role of the blood groups of the ABO system in the incidence and severity of infection.Este trabajo analiza las alteraciones hematológicas en enfermos con infección por SARS-CoV-2. Los pacientes de COVID-19, presentan en general una clínica respiratoria. Muchos pacientes con infección COVID-19 severa, desarrollan complicaciones tromboembólicas relacionadas con la coagulopatía, que se asocian a deterioro respiratorio y muerte. Los estudios de la hemostasia en estos pacientes pueden confundirse con el de otras alteraciones, que se ven de forma regular en la coagulación intravascular diseminada, sepsis o microangiopatía trombótica. Sin embargo, tanto la clínica como los datos de laboratorio, son diferentes a los presentados por esta enfermedad. La infección COVID-19 grave parece causar una profunda alteración del sistema de la coagulación con cambios inflamatorios combinados con lesiones endoteliales, con la liberación de factor Von Willebrand y activadores del plasminógeno. Esta coagulopatía contribuye a la trombosis microvascular, la deposición de fibrina y las complicaciones tromboembólicas.Todo ello, ha puesto de manifiesto la necesidad de utilizar tratamientos anticoagulantes, normalmente heparinas de bajo peso molecular, en dosis profilácticas o terapéuticas.Por otra parte, se discute la utilización del plasma de donante convaleciente para el tratamiento de esta enfermedad, y el papel de los grupos sanguíneos del sistema ABO en la incidencia y gravedad de la infección