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1.
Blood ; 139(19): 2931-2941, 2022 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-35007321

RESUMEN

The goal of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for patients with ET and PV at high risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment-naïve, high-risk patients with ET/PV. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (P = .80) at 12 months. At 24 to 36 months, CR was 20% to 17% for HU and 29% to 33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, whereas grade 3/4 adverse events were more frequent with PEG (46% vs 28%). At 12 months of treatment, there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment, PEG was more effective in normalizing blood counts and reducing driver mutation burden, whereas HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk patients with ET/PV. This trial was registered at www.clinicaltrials.gov as #NCT01259856.


Asunto(s)
Policitemia Vera , Trombocitemia Esencial , Trombosis , Progresión de la Enfermedad , Humanos , Hidroxiurea/efectos adversos , Interferón-alfa/efectos adversos , Policitemia Vera/tratamiento farmacológico , Policitemia Vera/genética , Trombocitemia Esencial/tratamiento farmacológico , Trombocitemia Esencial/genética , Trombosis/inducido químicamente , Trombosis/prevención & control
2.
Haematologica ; 109(3): 888-894, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37646655

RESUMEN

Autologous peripheral blood stem cell transplantation (aPBSCT) provides optimal outcomes in POEMS syndrome but the definition of the best treatment before aPBSCT remains to be defined because of the rarity of the disease and the heterogeneity of published case series. We collected clinical and laboratory data of patients with POEMS syndrome undergoing aPBSCT from 1998 to 2020 in ten Italian centers. The primary endpoint of the study was to evaluate the impact of prior therapies and mobilization regimen on outcome. We divided the patients into three groups: patients who did not receive any treatment before transplant (15 patients, group A: front-line), patients pre-treated with other agents (14 patients, group B) and patients treated with cyclophosphamide as their mobilizing regimen (16 patients, group C). The three groups did not show differences in terms of demographic and clinical characteristics. All 45 patients underwent aPBSCT after a high-dose melphalan conditioning regimen, with a median follow-up of 77 months (range, 37-169 months). The responses were not statistically different between the three groups (P=0.38). Progression-free and overall survival rates at 6 years were: 70% (95% confidence interval: 55-85%) and 91% (95% confidence interval: 82-99) 65%, respectively, and did not differ between the three groups. The cumulative incidence of transplant-related mortality and relapse was 4% and 36%, respectively. In conclusion, in a relatively large number of patients with POEMS syndrome, undergoing an autologous transplant, pre-treatment and disease status at transplant did not appear to have an impact on major transplant outcomes.


Asunto(s)
Síndrome POEMS , Trasplante de Células Madre de Sangre Periférica , Humanos , Síndrome POEMS/diagnóstico , Síndrome POEMS/terapia , Trasplante Autólogo , Autoinjertos , Ciclofosfamida/uso terapéutico
3.
Eur J Haematol ; 112(4): 577-584, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38183299

RESUMEN

Hemorrhagic cystitis (HC) is a highly impacting complication in allogeneic hematopoietic stem cell transplantation (HSCT), occurring in 12%-37% of patients. The impact of transplant- and patient-specific variables has been described, with a possible role for JCV and BKV, which may be cooperating with cytomegalovirus (CMV). Here, we analyze 134 letermovir-exposed, CMV-free patients, treated with the same cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, describing risk factors for HC. The overall incidence of HC was 23%. Patients with HLA mismatched transplant, higher comorbidity score, and receiving three alkylating agents with TBF (thiotepa, busulfan, and fludarabine) conditioning regimen had a higher risk of HC in multivariate analysis (OR: 4.48, 6.32, and 1.32, respectively). A HC-score including male gender, TBF conditioning, and HLA-mismatch stratifies the risk of HC in the first 100 days after HSCT. The role of BKV and JCV was not highly impacting in those patients, suggesting a possible synergistic effect between CMV and JCV in causing HC. HC can be interpreted as the combination of patient-related factors, chemotherapy-related toxicities-especially due to alkylating agents-and immunological elements.


Asunto(s)
Acetatos , Cistitis Hemorrágica , Cistitis , Infecciones por Citomegalovirus , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Quinazolinas , Humanos , Masculino , Citomegalovirus , Cistitis/diagnóstico , Cistitis/epidemiología , Cistitis/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Factores de Riesgo , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/etiología , Alquilantes , Enfermedad Injerto contra Huésped/etiología , Estudios Retrospectivos
4.
Am J Hematol ; 99(5): 938-945, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38450790

RESUMEN

BACKGROUND: Allogeneic hemopoietic stem cell transplantation (HSCT) currently remains the only curative treatment for patients with myelofibrosis (MF). Transplant related mortality (TRM) and relapse, remain two significant complications which need to be addressed. AIMS: The aim of this manuscript is to review current available reports on changes which have recently occurred, to improve the outcome of MF patients undergoing an allogeneic HSCT. METHODS: Published papers were used to analyze different aspects of allogeneic HSCT. RESULTS: Changes and updates are provided on selection of patients, prognostic systems, managing splenomegaly, conditioning regimens, predicting transplant outcome, stem cell sources, stem cell donors, graft versus host disease (GvHD) prophylaxis, patients with blast phase, hematopoietic reconstitution, disease markers, donor chimerism, and treatment of relapse. CONCLUSIONS: The review outlines new transplant platforms which are now available for patients with myelofibrosis, together with persisting problems, among which, older age combined with marrow fibrosis and an inflammatory disease. Relapse also requires aggressive monitoring of drivers mutations, and early cellular therapy.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Mielofibrosis Primaria , Humanos , Trasplante Homólogo/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Resultado del Tratamiento , Recurrencia Local de Neoplasia/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Crónica , Recurrencia , Medición de Riesgo , Acondicionamiento Pretrasplante/efectos adversos
5.
Philos Trans A Math Phys Eng Sci ; 382(2278): 20230353, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39069756

RESUMEN

This article focuses on characterizing a class of quasi-periodic metamaterials created through the repeated arrangement of an elementary cell in a fixed direction. The elementary cell consists of two building blocks made of elastic materials and arranged according to the generalized Fibonacci sequence, giving rise to a quasi-periodic finite microstructure, also called Fibonacci generation. By exploiting the transfer matrix method, the frequency band structure of selected periodic approximants associated with the Fibonacci superlattice, i.e. the layered quasi-periodic metamaterial, is determined. The self-similarity of the frequency band structure is analysed by means of the invariants of the symplectic transfer matrix as well as the transmission coefficients of the finite clusters of Fibonacci generations. A high-frequency continualization scheme is then proposed to identify integral-type or gradient-type non-local continua. The frequency band structures obtained from the continualization scheme are compared with those derived from the Floquet-Bloch theory to validate the proposed scheme. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 1).'

6.
Philos Trans A Math Phys Eng Sci ; 382(2279): 20230355, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39129410

RESUMEN

The present research focuses on a continuum description of stratified metamaterials achieved through the superposition of layers with alternating chirality. Each layer is constructed as a periodic assembly of centre-symmetric periodic cells, formed by a recurring arrangement of rigid circular discs connected by elastic ligaments. The layers are interconnected through elastic pins passing through the centres of aligned discs, allowing for either restrained or free relative rotation. A micropolar continuum model is used to describe each individual layer. The overall response of the metamaterials to in-plane forces is derived using a multi-field non-local model, expressed in terms of the average and difference of displacement and rotational fields. The overall micropolar and standard (Cauchy) constitutive tensors have been determined in closed form. The validity of the equivalent generalized micropolar model has been confirmed through comparison with discrete Lagrangian solutions of representative examples. In addition, a detailed analysis of a pseudo-indentation test has been carried out. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 2)'.

7.
Br J Haematol ; 201(1): 86-94, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36503182

RESUMEN

Cytokine release syndrome (CRS) and consumptive coagulopathy can complicate the treatment with chimeric antigen receptor T (CAR-T) cells. The modified version of the Endothelial Activation and Stress Index (mEASIX), a score derived from haematopoietic stem cell transplantation, combines platelets, C-reactive protein (CRP), and lactate dehydrogenase (LDH) and has been correlated with CRS and endothelial biomarkers. In 38 consecutive patients with aggressive lymphoproliferative disease we measured a coagulative laboratory panel at baseline and early after infusion of anti-CD19 CAR-T. The panel was investigated also in the presence of CRS graded 2 or higher, or immune effector cell-associated neurotoxicity syndrome (ICANS). Moreover, we examined the relationship between mEASIX, coagulation biomarkers, and toxicities of CAR-T cells. During CRS grade 2 or higher, we found increased prothrombin time (PT) and activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, factor VIII (FVIII), and von Willebrand factor (vWF) antigen levels, and decreased platelet count and antithrombin levels. The occurrence of immune effector cell-associated neurotoxicity syndrome was associated with higher PT values, D-dimer, FVIII, and vWF levels, and decreased fibrinogen levels and platelet count. A higher mEASIX score correlated with increased aPTT values, fibrinogen, D-dimer, FVIII and vWF levels, and decreased antithrombin levels. Baseline mEASIX was predictive for consumptive coagulopathy and CRS graded 2 or higher, and for progression-free survival and overall survival.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Coagulación Intravascular Diseminada , Receptores Quiméricos de Antígenos , Humanos , Antitrombinas , Biomarcadores , Síndrome de Liberación de Citoquinas/etiología , Coagulación Intravascular Diseminada/etiología , Fibrinógeno , Inmunoterapia Adoptiva/efectos adversos , Pronóstico , Linfocitos T , Factor de von Willebrand
8.
Transfus Apher Sci ; 62(4): 103708, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37003931

RESUMEN

The current COVID-19 pandemic has placed unprecedented stress on the healthcare system, including HSCT. Several international organizations have created guidelines for managing different aspects of HSCT in the context of the pandemic. Comparing 2019 and 2020, our transplant center performed the same number of transplants. In both periods, transplants were mainly for patients with acute leukemia; thus, the urgency criteria was respected in light of pandemic restraints. Transplants by sibling donors and cord blood units remained the same, while transplants by unrelated donors were increased, in particular from European registries, and transplants by haploidentical donors were decreased. This change was made in light of the necessity of cryopreserving all apheresis products. We decided against cryopreserving bone marrow products due to the greater risk of drastic reduction in CD34 + cell count during the process. For urgent cases with only a haploidentical donor available, we opted for the use of PBSC following stimulation with G-CSF. GvHD prophylaxis was performed with PTCY on days + 3 + 5, cyclosporine with tapering from day + 100, and mycophenolic acid until day + 90 post-HSCT. Post-transplant outcomes such as graft failure, sepsis, and GVHD were not affected by the changes implemented. As a result of logistic difficulties, we halted our Car-T program from the start of the lockdown in March 2020 until September 2020. In accord with international guidelines, we were able to continue our HSCT program in the order to ensure a lifesaving treatment for patients with hematologic diseases for whom this procedure cannot be postponed.


Asunto(s)
COVID-19 , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Pandemias , Control de Enfermedades Transmisibles , Trasplante de Células Madre Hematopoyéticas/métodos , Donante no Emparentado , Enfermedad Injerto contra Huésped/prevención & control , Acondicionamiento Pretrasplante/métodos
9.
J Psychosoc Oncol ; 41(6): 687-703, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36825453

RESUMEN

PURPOSE: Depressive disorders are the most common manifestation of psychological distress in allogenic hematopoietic stem cell transplantation. Few studies have yet investigated the relationship between therapeutic educational interventions and outcomes in these patients with specific attention to those related to mental health. Aim of this study was to understand how much educational intervention can represent a protective factor in preventing psycho-emotional distress-related issues in this setting. DESIGN: A prospective observational study of a multicenter cohort was conducted. PARTICIPANTS: Adult patients undergoing allogeneic hematopoietic stem cell transplantation. METHODS: A pre-transplant therapeutic educational programme was offered to a cohort of adult patients undergoing allo-HSCT recruited in ten transplant centers of the GITMO network between May 2018 and January 2019. Depression, Anxiety and Stress scale was used to collect data on psycho-emotional distress at admission (T0), at the day of transplant (T1) and at discharge (T2). Descriptive data were collected and reported, and comparative analyses were done among patients who were compliant with the pre-transplant educational intervention and those who did not (for any reason). FINDINGS: A cohort of 133 allo-HSCT patients was observed. In patients who did not receive pre-transplant educational intervention, higher levels of depression at admission (p = 0.01) and at the day of transplant (p = 0.03), higher levels of anxiety (p = 0.01 and p = 0.01 respectively) as well as higher levels of stress (p < 0.01 and p = 0.01) were observed. Problem solving and "face to face" interview were the best methods to provide education to patients. Those who received pre-transplant education through "face-to-face" interview reported significant low levels of depression during the whole hospital stay period (p < 0.01; p = 0.01; p = 0.01) and less anxiety and stress at admission (p < 0.05 and p = 0.01 respectively). Depression was more represented in female than male participants at T0 (16.5% vs 9.0%; p = 0.01), while among T0 and T2 the males had a significant higher increasing of depression than females (p = 0.03). CONCLUSION: Our study demonstrated that pretreatment therapeutic educational programs with specific learning modalities can be effective in limiting the potential risk of developing moderate-to-severe anxiety-depressive states and stress symptoms related to allo-HSCT. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: Further studies are needed to confirm our results and to understand whether containing psycho-emotional distress can have any relationship with medium- and long-term post-transplant complications.

10.
Support Care Cancer ; 30(6): 4953-4959, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35179653

RESUMEN

PURPOSE: Hemorrhagic cystitis (HC) is a frequent complication of allogeneic hematopoietic stem-cell transplantation (HSCT). HC worsens transplant outcomes and patient wellbeing in terms of pain, hospitalization, and need for supportive care. A deeper understanding of the risk factors of HC may lead to more intensive prevention in high-risk patients. METHODS: In this report, we analyzed 237 consecutive patients who received HSCT with the aim of identifying possible risk factors for HC and their consequences, with a particular focus on transplant- and gender-related risk factors. RESULTS: HC occurred in 17% of patients, with a higher incidence in males (21% vs 11%, p = 0.03). Risk factors identified for HC included age over 55 years, male recipient, HLA mismatch, reduced intensity conditioning, and cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. Increased HC was seen in patients with grade II-IV acute GVHD and detectable BKV and JCV viruria. In a multivariate model, increased age remained significant (p = 0.013). Patients with HC had longer hospitalizations and increased non-relapse mortality (NRM). Among male recipients, independent risk factors for HC included age (p = 0.016) and prostate volume (p = 0.016). Prostatic hyperplasia (volume more than 40 cm3) occurred in 33% of male patients, of which 32% developed HC (compared with 16% of patients without prostatic hyperplasia; p = 0.032). CONCLUSIONS: Age is the most important risk factor for HC. Additional potential risk factors include cyclophosphamide-based GVHD prophylaxis and HLA mismatch. Among male recipients, prostatic hyperplasia is an additional independent risk factor. As HC is common and associated with prolonged hospitalization, more intensive prophylactic strategies should be considered in high-risk patients.


Asunto(s)
Cistitis , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Hiperplasia Prostática , Ciclofosfamida/uso terapéutico , Cistitis/inducido químicamente , Cistitis/etiología , Femenino , Enfermedad Injerto contra Huésped/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/etiología , Humanos , Masculino , Persona de Mediana Edad , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/complicaciones , Estudios Retrospectivos , Factores de Riesgo
11.
Cytotherapy ; 23(7): 635-640, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33423867

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has deeply modified the complex logistical process underlying allogeneic hematopoietic stem cell transplant practices. AIM: In light of these changes, the authors compared data relative to allogeneic transplants carried out from 2018 at their center before (n = 167) and during the pandemic (n = 45). METHODS: The authors examined patient characteristics, donor and graft types, cell doses and main transplant outcomes. Moreover, the authors evaluated the rise of costs attributable to additional COVID-19-related procedures as well as the risk of adverse events these procedures conveyed to grafts or recipients. RESULTS: Overall, the number of transplants did not decrease during the pandemic, whereas patients at high relapse risk were prioritized. Transplants were mainly from matched unrelated donors, with a significant decrease in haploidentical related donors. Moreover, the use of bone marrow as a graft for haploidentical transplant was almost abandoned. Cryopreservation was introduced for all related and unrelated apheresis products, with a median storage time of 20 days. Notably, transplant outcomes (engraftment, acute graft-versus-host disease and non-relapse mortality) with cryopreserved products were comparable to those with fresh products. CONCLUSIONS: Considering that the emergency situation may persist for months, cryopreserving allogeneic grafts can offer a lifesaving opportunity for patients whose allogeneic transplant cannot be postponed until after the end of the COVID-19 pandemic.


Asunto(s)
COVID-19/epidemiología , Trasplante de Células Madre Hematopoyéticas , Pandemias , COVID-19/virología , Criopreservación , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2/fisiología , Donantes de Tejidos , Trasplante Homólogo , Resultado del Tratamiento
12.
Eur J Haematol ; 107(5): 573-582, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34297437

RESUMEN

We studied pretransplant minimal residual disease (MRD) in 224 patients (median age 44 years; range 17-65) with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplant (HSCT) in complete remission. MRD was evaluated on marrow samples using multicolor flow cytometry and assessment of WT1 gene expression. Both methods showed a strong prognostic value and their combination allowed the identification of three groups of patients with different risk of relapse. In multivariate analysis, combined MRD was the only predictor of cumulative incidence of relapse, regardless of donor type, conditioning regimen, first or second CR at HSCT, HSCT year, and ELN risk group. Multivariate regression model showed that only negative combined MRD status (P < .001) and myeloablative conditioning (P = .004) were independently associated with better OS. Among MRD-positive patients, a reduced incidence of relapse was observed in patients receiving haplo transplant (P < .05) and in patients who showed grade II-IV aGVHD (P < .03). In patients with negative combined MRD, the intensity of conditioning regimen did not affect the overall favorable outcome. We suggest that pretransplant MRD evaluation combined with transplant-related factors can identify AML patients at higher risk for relapse and might help in defining the overall transplant strategy.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Neoplasia Residual , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante Homólogo , Resultado del Tratamiento
13.
Am J Hematol ; 96(11): 1532-1538, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34536293

RESUMEN

The number of patients with myelofibrosis (MF) undergoing an allogeneic hemopoietic stem cell transplantation (HSCT) is increasing: in the analysis of the European Group for Blood and Marrow Transplantation (EBMT) the number of MF has increased from 515 in 2014 to 748 in 2018 . This reflects the fact that HSCT is currently the only curative treatment, capable of inducing prolonged disease-free survival. Nevertheless, several problems prevent more patients from undergoing an allogeneic HSCT: we will be discussing indications for HSCT, comorbidities, splenomegaly, older age and disease phase. Donor type and stem cell source are less of a problem. Several transplant platforms exist, including different strategies for graft versus host disease (GvHD) prophylaxis, Age tailored conditioning regimens need to be implemented, to allow older and fragile patients to undergo an allogeneic HSCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mielofibrosis Primaria/terapia , Animales , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Medición de Riesgo , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/métodos
14.
Am J Hematol ; 96(2): 234-240, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33146914

RESUMEN

The aim of this retrospective study was to assess the rate of full donor chimerism (F-DC) in patients with myelofibrosis, prepared for an allogeneic stem cell transplant, with one or two alkylating agents. We analyzed 120 patients with myelofibrosis, for whom chimerism data were available on day +30. There were two groups: 42 patients were conditioned with one alkylating agent (ONE-ALK), either thiotepa or busulfan or melphalan, in combination with fludarabine, whereas 78 patients were prepared with two alkylating agents, thiotepa busulfan and fludarabine (TBF). Patients receiving TBF were older (57 vs 52 years), were less frequently splenectomized pre-HSCT (31% vs 59%), had more frequently intermediate-2/high DIPSS scores (90% vs 74%), were grafted more frequently from alternative donors (83% vs 33%) and received more frequently ruxolitinib pre-HSCT (26% vs 7%). The proportion of patients with F-DC on day +30, in the TBF vs the ONE-ALK group, was respectively 87% vs 45% (P < .001). The 5-year cumulative incidence of relapse was 9% in the TBF group, vs 43% for the ONE-ALK group (P < .001). The 5-year actuarial disease-free survival was 63% for TBF and 38% for the ONE-ALK group (P = .004). In conclusion, early full donor chimerism is a prerequisite for long term control of disease in patients with myelofibrosis, undergoing an allogeneic HSCT. The combination of two alkylating agents in the conditioning regimen, provides a higher chance of achieving full donor chimerism on day+30, and thus a higher chance of long term disease free survival.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mielofibrosis Primaria/mortalidad , Mielofibrosis Primaria/terapia , Quimera por Trasplante , Acondicionamiento Pretrasplante , Adulto , Anciano , Aloinjertos , Busulfano/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Esplenectomía , Tasa de Supervivencia , Tiotepa/administración & dosificación
15.
Biol Blood Marrow Transplant ; 26(10): 1915-1922, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32645444

RESUMEN

The timing of immunosuppressive therapy used in combination with post-transplantation cyclophosphamide (PTCY) in haploidentical hematopoietic stem cell transplant (haplo-HSCT) is not standardized. We evaluated the schedules of immunosuppression therapy after haplo-HSCT in 509 patients with acute leukemia receiving PTCY on days +3 and +4 along with tacrolimus (group 1; n = 215), with cyclosporine A (CSA) and mycophenolate mofetil (MMF) from day +5 (group 2; n = 170), or CSA + MMF from day 0 or 1 with PTCY on days +3 and +5 (group 3; n = 124). Compared with the other 2 groups, patients in group 3 were younger (median age, 46 years; P = .02) and more often received bone marrow (77%; P < .01) and a regimen containing thiotepa, fludarabine, and busulfan (84%; P< .01). At 2 years, overall survival was 44% was in group 1, 48% in group 2, and 59% in group 3 (P= .15); leukemia-free survival (LFS) was 43%, 46%, and 53% (P= .05); and refined graft-versus-host disease-free, relapse-free survival (rGRFS) was 33%, 39%, and 36% (P = .02). The incidence of grade II-IV acute GVHD was 25% in group 1, 39% in group 2, and 18% in group 3 (P< .01); incidence of chronic GVHD was 25%, 21%, and 24% (P= .50); relapse incidence was 36%, 37%, and 26% (P= .02); and nonrelapse mortality was 26%, 20%, and 21% (P= .35). On multivariate analysis, early start of immunosuppression therapy at day +1 followed by PTCY was associated with a better LFS (hazard ratio [HR], .58; P= .02) and improved rGRFS (HR, .62; P = .02). In this study, the timing of immunosuppression influenced the outcomes of haplo-HSCT with PTCY. An early start of CSA + MMF with PTCY administered on days +3 and +5 improves LFS and rGRFS.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Médula Ósea , Ciclofosfamida/uso terapéutico , Humanos , Persona de Mediana Edad , Acondicionamiento Pretrasplante , Trasplante Haploidéntico
16.
Biol Blood Marrow Transplant ; 26(4): 698-703, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31875522

RESUMEN

This is a multicenter retrospective comparison of 2 myeloablative conditioning regimens in 454 patients with acute myeloid leukemia (AML) in remission: busulfan (4 days) and fludarabine (BUFLU) versus thiotepa, busulfan, and fludarabine (TBF). Eligible for this study were patients allografted between January 2008 and December 2018 in 10 transplant centers, with AML in first or second remission: 201 patients received BUFLU, whereas 253 received TBF. The 2 groups (BUFLU and TBF) were comparable for age (P = .13) and adverse AML risk factors (P = .3). The TBF group had more second remissions and more haploidentical grafts. The donor type included HLA-identical siblings, unrelated donors, and family haploidentical donors. The 5-year cumulative incidence of nonrelapse mortality (NRM) was 19% for BUFLU and 22% for TBF (P = .8), and the 5-year cumulative incidence of relapse was 30% and 15%, respectively (P = .0004). The 5-year actuarial survival was 51% for BUFLU and 68% for TBF (P = .002). In a multivariate Cox analysis, after correcting for confounding factors, the use of TBF reduced the risk of relapse compared with BUFLU (P = .03) and the risk of death (P = .03). In a matched pair analysis of 108 BUFLU patients matched with 108 TBF patients, with the exclusion of haploidentical grafts, TBF reduced the risk of relapse (P = .006) and there was a trend for improved survival (P = .07). Superior survival of patients receiving TBF as compared with BUFLU is due to a reduced risk of relapse, with comparable NRM. The survival advantage is independent of donor type and AML risk factors.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Busulfano/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Leucemia Mieloide Aguda/terapia , Estudios Retrospectivos , Tiotepa , Acondicionamiento Pretrasplante , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico
17.
Haematologica ; 105(5): 1223-1231, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31582549

RESUMEN

This follow-up study of a randomized, prospective trial included 192 patients with newly diagnosed severe aplastic anemia receiving antithymoglobulin and cyclosporine, with or without granulocyte colony-stimulating factor (G-CSF). We aimed to evaluate the long-term effect of G-CSF on overall survival, event-free survival, probability of secondary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), clinical paroxysmal nocturnal hemoglobinuria, relapse, avascular osteonecrosis and chronic kidney disease. The median follow-up was 11.7 years (95% CI, 10.9-12.5). The overall survival rate at 15 years was 57±12% in the group given G-CSF and 63±12% in the group not given G-CSF (P=0.92); the corresponding event-free survival rates were 24±10% and 23±10%, respectively (P=0.36). In total, 9 patients developed MDS or AML, 10 only a clonal cytogenetic abnormality, 7 a solid cancer, 18 clinical paroxysmal nocturnal hemoglobinuria, 8 osteonecrosis, and 12 chronic kidney disease, without any difference between patients treated with or without G-CSF. The cumulative incidence of MDS, AML or isolated cytogenetic abnormality at 15 years was 8.5±3% for the G-CSF group and 8.2±3% for the non-G-CSF group (P=0.90). The cumulative incidence of any late event including myelodysplastic syndrome or acute myeloid leukemia, isolated cytogenetic abnormalities, solid cancer, clinical paroxysmal nocturnal hemoglobinuria, aseptic osteonecrosis, chronic kidney disease and relapse was 50±12% for the G-CSF group and 49±12% for the non-G-CSF group (P=0.65). Our results demonstrate that it is unlikely that G-CSF has an impact on the outcome of severe aplastic anemia; nevertheless, very late events are common and eventually affect the prognosis of these patients, irrespectively of their age at the time of immunosuppressive therapy (NCT01163942).


Asunto(s)
Anemia Aplásica , Suero Antilinfocítico , Anemia Aplásica/diagnóstico , Anemia Aplásica/tratamiento farmacológico , Anemia Aplásica/epidemiología , Suero Antilinfocítico/uso terapéutico , Médula Ósea , Ciclosporina/uso terapéutico , Estudios de Seguimiento , Factor Estimulante de Colonias de Granulocitos , Granulocitos , Humanos , Inmunosupresores/uso terapéutico , Estudios Prospectivos
18.
Haematologica ; 105(1): 47-58, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31537691

RESUMEN

Donor lymphocyte infusion has been used in the management of relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. It can eradicate minimal residual disease or be used to rescue a hematologic relapse, being able to induce durable remissions in a subset of patients. With the increased use of haploidentical hematopoietic cell transplantation, there is renewed interest in the use of donor lymphocytes to either treat or prevent disease relapse post transplant. Published retrospective and small prospective studies have shown encouraging results with therapeutic donor lymphocyte infusion in different haploidentical transplantation platforms. In this consensus paper, finalized on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize the available evidence on the use of donor lymphocyte infusion from haploidentical donor, and provide recommendations on its therapeutic, pre-emptive and prophylactic use in clinical practice.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Consenso , Humanos , Linfocitos , Estudios Prospectivos , Estudios Retrospectivos
19.
Cytotherapy ; 22(3): 158-165, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32057614

RESUMEN

We analyzed data relative to cell content in 88 consecutive patients receiving HLA haploidentical bone marrow (BM) transplants with post-transplantation cyclophosphamide (PT-CY). Median age was 54.5 (range, 17-72); diagnoses were acute leukemia (n = 46), lymphoproliferative disorders (n = 24), myelofibrosis (n = 11) and myelodysplastic syndromes (n = 5). Total nucleated cell (TNC) and CD34+, CD3+, CD4+ and CD8+ cell doses were stratified as higher than first, second and third quartile and the dose effect on various clinical outcomes was assessed. Median time to engraftment was 17 days for neutrophils and 24 days for platelets. To receive a dose of TNC ≥3.2 x 106/kg or CD34+ cells ≥2.7 x 106/kg significantly shortened the time to neutrophil and platelet engraftment and reduced the blood product requirements in the 30-day period after transplantation. Overall, TNC and CD34+ cell doses had no effect on acute graft-versus-host disease (GVHD) incidence, whereas patients receiving higher CD3+ and CD8+ cell doses seemed to have less chronic GVHD. No effect on non-relapse mortality, progression-free survival and overall survival was observed at different cell dose thresholds. These data suggest that in HLA haploidentical BM transplant with PT-CY, appropriate cell doses are relevant to the engraftment. The association between low CD3+/CD8+ cells and chronic GVHD deserves further investigation.


Asunto(s)
Trasplante de Médula Ósea , Ciclofosfamida/farmacología , Trasplante Haploidéntico , Adolescente , Adulto , Anciano , Trasplante de Médula Ósea/efectos adversos , Niño , Preescolar , Quimerismo , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/patología , Neutrófilos/trasplante , Transfusión de Plaquetas , Modelos de Riesgos Proporcionales , Donantes de Tejidos , Trasplante Haploidéntico/efectos adversos , Resultado del Tratamiento , Adulto Joven
20.
BMC Cancer ; 20(1): 1140, 2020 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-33234127

RESUMEN

BACKGROUND: Allogeneic stem cell transplantation from haploidentical donor using an unmanipulated graft and post-transplantation cyclophosphamide (PT-Cy) is growing. Haploidentical transplantation with PT-Cy showed a major activity in Hodgkin lymphoma (HL), reducing the relapse incidence. The most important predictive factor of survival and toxicity was disease status before transplantation, which was better in patients with well controlled disease. METHODS: We included 198 HL in complete (CR) or partial remission (PR) before transplantation. Sixty-five patients were transplanted from haploidentical donor and 133 from a HLA identical donor (both sibling and unrelated donors). Survival analysis was defined according to the EBMT criteria. Survival curves were generated by using Kaplan-Meier method and differences between groups were compared by the log rank test or by the log rank test for trend when appropriated. RESULTS: The PFS, OS, and RI were significantly better in patients in CR compared to PR (55% vs 29% p = 0.001, 74% vs 55% p = 0.03, 27% vs 55% p <  0.001, respectively). The 2-year PFS was significantly better for HAPLO than HLA-id (63% vs 37%, p = 0.03), without difference in OS. The 1-year NRM was not different. The 2-year relapse incidence (RI) was lower in the HAPLO group (24% vs 44%, p = 0.008). Patients in CR receiving haplo HSCT showed higher 2-year PFS and lower 2-year RI than those allografted with HLA-id donor (75% vs 47%, p <  0.001 and 11% vs 34%, p < 0.001, respectively). In multivariate analysis, donor type and disease status before transplantation were independent predictors of PFS as well as they predict the risk of relapse. Disease status at transplantation and age were independently associated to OS. CONCLUSIONS: Nonetheless this is a retrospective study, limiting the wide applicability of results, data from this analysis suggest that HLA mismatch can induce a strong graft versus lymphoma effect leading to an enhanced PFS.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas/mortalidad , Enfermedad de Hodgkin/mortalidad , Donantes de Tejidos/provisión & distribución , Trasplante Haploidéntico/mortalidad , Adolescente , Adulto , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Hermanos , Tasa de Supervivencia , Acondicionamiento Pretrasplante , Trasplante Homólogo , Adulto Joven
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