Carme Canals

Allogeneic hematopoietic stem cell transplantation in children and adolescents with recurrent and refractory Hodgkin lymphoma: an analysis of the European Group for Blood and Marrow Transplantation

Ninety-one children and adolescents 18 years or younger after allogeneic hematopoietic stem cell transplantation (HSCT) for relapsed or refractory Hodgkin lymphoma (HL) were analyzed. Fifty-one patients received reduced intensity conditioning (RIC); 40 patients received myeloablative conditioning (MAC). Nonrelapse mortality (NRM) at 1 year was 21% (+/- 4%), with comparable results after RIC or MAC. Probabilities of relapse at 2 and 5 years were 36% (+/- 5%) and 44% (+/- 6%), respectively. RIC was associated with an increased relapse risk compared with MAC; most apparent beginning 9 months after HSCT (P = .01). Progression-free survival (PFS) was 40% (+/- 6%) and 30% (+/- 6%) and overall survival (OS) was 54% (+/- 6%) and 45% (+/- 6%) at 2 and 5 years, respectively. Disease status at HSCT was predictive of PFS in multivariate analysis (P < .001). Beyond 9 months, PFS after RIC was lower compared with MAC (P = .02). Graft-versus-host disease did not affect relapse rate and PFS. In conclusion, children and adolescents with recurring HL show reasonable results with allogeneic HSCT. Especially patients allografted in recent years with good performance status and chemosensitive disease show highly encouraging results (PFS: 60% +/- 27%, OS: 83% +/- 15% at 3 years). Because relapse remains the major cause of treatment failure, additional efforts to improve disease control are necessary.

Matched unrelated donor stem cell transplant in 131 patients with follicular lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.

Matched unrelated donor stem cell transplantation (MUD‐SCT) provides the only curative option for patients with follicular lymphoma (FL) who fail conventional therapies and do not have a sibling donor. The purpose of this study was to analyse the outcome of patients with FL treated with MUD‐SCT included in the European Group for Blood and Marrow Transplantation registry. 131 patients treated with reduced‐intensity conditioning (RIC, n = 87) or conventional myeloablative (CONV, n = 44) MUD‐SCT between 2000 and 2005 were included. Median time from diagnosis to MUD‐SCT was 47 months and the median number of previous therapeutic regimens was 4 (previous autograft: 47%). RIC recipients were significantly older, with a longer interval from diagnosis to MUD‐SCT and had failed a previous autograft more frequently than CONV recipients. Non‐relapse mortality (NRM) was 24% and 30% at 100‐d and 1‐year, respectively. After a median follow‐up of 36 months, 17% of the patients developed disease progression, the 3‐year progression‐free survival (PFS) being 47%. Three‐year overall survival (OS) for the whole series was 51%. On multivariate analysis, RIC regimens were associated with at lower NRM and a significantly longer PFS and OS. This retrospective study demonstrated that MUD‐SCT results, even in heavily pre‐treated populations, in a meaningful PFS and OS.

Post-Thaw Viable CD45+ Cells and Clonogenic Efficiency are Associated with Better Engraftment and Outcomes after Single Cord Blood Transplantation in Adult Patients with Malignant Diseases

The quantity of cells is widely accepted as the main factor influencing the outcome after umbilical cord blood transplantation (UCBT) however, the quality of the cord blood units (CBUs) has been less studied. In order to determine the impact of qualitative variables in UCBT outcomes, we conducted a multicenter retrospective study in adult patients with hematological malignancies who underwent single UCBT after a common myeloablative conditioning regimen. One hundred and ten patients from 3 institutions [median age, 35 years (range 18-55)] were included. Quantitative (TNC and total CD34+cells) and qualitative variables [viable CD45+ (vCD45+), vCD34+ and clonogenic efficiency [(CLONE), quotient of post-thaw colony-forming units (CFU)] and pre-freeze CD34+ cells predicted engraftment in univariate analysis however, only 2 qualitative variables remained significant in the multivariate analysis. Infusion of more than 2 × 10(7) post-thaw vCD45+ cells per kilogram was significantly associated with faster neutrophil (P = .01), platelet engraftment (P = .01), higher disease-free (P = .01) and overall survival (0.02). In addition, CLONE ≥ 20% predicted a faster neutrophil (P = .005), platelet engraftment (P = .01) and contributed to decrease the non-relapse mortality (P = .02). Our study suggests that the vCD45+ cells dose and CLONE are powerful surrogate markers of graft quality and can potentially help on CBUs selection if tested with representative reference samples.

Early and Long-Term Impaired T Lymphocyte Immune Reconstitution after Cord Blood Transplantation with Antithymocyte Globulin

Immune reconstitution is crucial to the success of allogeneic hematopoietic stem cell transplantation. Umbilical cord blood transplantation (UCBT) has been associated with delayed immune reconstitution. We characterized the kinetics and investigated the risk variables affecting recovery of the main lymphocyte subsets in 225 consecutive pediatric and adult patients (males, n = 126; median age, 15; range, .3 to 60; interquartile range, 4 to 35) who underwent myeloablative single UCBT between 2005 and 2015 for malignant and nonmalignant disorders. Low CD4+ and CD8+ T cell counts were observed up to 12 months after UCBT. In contrast, B and natural killer cells recovered rapidly early after transplantation. In a multivariate regression model, factors favoring CD4+ T cell recovery ≥ 200 cells/µL were lower dose antithymocyte globulin (ATG) (hazard ratio [HR], 3.93; 95% confidence interval [CI], 2.3 to 5.83; P = .001), negative recipient cytomegalovirus (CMV) serostatus (HR, 3.76; 95% CI, 1.9 to 5.74; P = .001), and younger age (HR, 2.61; 95% CI, 1.01 to 3.47; P = .03). Factors favoring CD8+ T cell recovery ≥ 200 cells/µL were lower dose ATG (HR, 3.03; 95% CI, 1.4 to 5.1; P = .03) and negative recipient CMV serostatus (HR, 1.9; 95% CI, 1.63 to 2.15; P = .01). Our results demonstrate the significant negative impact of ATG on lymphocyte recovery. A reduction of the dose or omission of ATG could improve immune reconstitution and perhaps reduce opportunistic infections after UCBT.

Valoración de la mutación V617F del gen JAK2 en síndromes mieloproliferativos crónicos con cromosoma Filadelfia negativo

Fundamento y objetivo: La mutacion V617F en el gen de la tirosincinasa JAK2 esta implicada en la genesis de algunos sindromes mieloproliferativos cronicos (SMP) como la policitemia vera (PV), la trombocitemia esencial (TE) y la mielofibrosis (MF) idiopatica. Se ha valorado el papel diagnostico de esta mutacion en los SMP y se ha comparado con la formacion espontanea de colonias eritroides (BFU-E-ESP). Pacientes y metodo: Se incluyo a 146 pacientes, de los que 81 presentaban SMP (27 PV, 28 TE, 11 MF y 15 leucemia mieloide cronica), 28 con eritrocitosis secundaria o trombocitosis reactiva, 8 SMP/sindromes mielodisplasicos y 29 con otras hemopatias. En 54 casos se valoro tambien la BFU-E-ESP. La fuente de las celulas hemopoyeticas para obtener ADN fue la sangre periferica en 122 pacientes, la medula osea en 33, las unidades formadoras de colonias eritroides con estimulacion con eritropoyetina en 14 y las BFU-E-ESP en 24. La mutacion V617F se efectuo usando una reaccion en cadena de la polimerasa especifica de alelo. Resultados: El 96% de las PV, el 59% de las TE y el 63,6% de las MF presentaron dicha mutacion. La concordancia diagnostica entre BFU-E-ESP y la mutacion fue excelente (indice kappa = 0,93; acuerdo en lo positivo del 97% y acuerdo en lo negativo del 95%). Se pudo valorar la mutacion en 119 de los 122 pacientes en que se uso sangre periferica, en los 33 en que se uso medula osea y en la mitad de aquellos en que se utilizaron las colonias eritroides como fuentes de ADN. Conclusiones: La mutacion V617F del gen JAK2 esta presente en casi todas las PV y en la mitad de las TE y de las MF. Hay una excelente concordancia entre la presencia de esta mutacion y BFU-E-ESP. Finalmente, se puede usar diferentes fuentes celulares en la obtencion de ADN para el estudio de esta mutacion.

Few and Nonsevere Adverse Infusion Events Using an Automated Method for Diluting and Washing before Unrelated Single Cord Blood Transplantation

Graft dilution and DMSO washing before cord blood (CB) administration using an automated system may offer low incidence of adverse infusion events (AIE), ensuring reproducible cell yields. Hence, we analyzed the incidences and significance of immediate AIE, cellular yield, and engraftment after single CB infusion. One hundred and fifty-seven patients (median age, 20 years; range, 1 to 60) received a single CB unit for treatment of hematologic and nonhematologic malignancies with myeloablative conditioning after graft dilution and washing. The median total nucleated cell (TNC) doses was 3.4 × 10(7)/kg (range, 2 to 26) and the median post-thaw recovery was 84% (range, 45 to 178). The cumulative incidence of neutrophil engraftment at 50 days was 84% (95% confidence interval [CI], 83 to 93). A total of 118 immediate AIE were observed in fifty-two (33%) patients. All reported AIE were transient, graded from 1 to 2 by Common Terminology Adverse Events version 4. The most frequent toxicity was cardiovascular but without any life-threatening reaction. Infused TNC, recipients weight, and rate of infusion per kilogram were risk factors associated with cardiovascular AIE in multivariate analysis (odds ratio [OR], 1.2 (95% CI, 1.1 to 1.4); P < .001; OR, .94 (95% CI, .9 to .97); P < .001; and OR, 1.5 (95% CI, 1.2 to 1.8); P < .001; respectively). In summary, use of an automated method for graft washing before CB administration showed low incidence of AIE without compromising cell yields and engraftment. Infused TNC dose, recipients weight, and rate of infusion per kilogram were risk factors associated with infusion reactions.

Matched unrelated donor stem cell transplant in 131 patients with follicular lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation: Matched Unrelated Donor SCT in Follicular Lymphoma

Matched unrelated donor stem cell transplantation (MUD‐SCT) provides the only curative option for patients with follicular lymphoma (FL) who fail conventional therapies and do not have a sibling donor. The purpose of this study was to analyse the outcome of patients with FL treated with MUD‐SCT included in the European Group for Blood and Marrow Transplantation registry. 131 patients treated with reduced‐intensity conditioning (RIC, n = 87) or conventional myeloablative (CONV, n = 44) MUD‐SCT between 2000 and 2005 were included. Median time from diagnosis to MUD‐SCT was 47 months and the median number of previous therapeutic regimens was 4 (previous autograft: 47%). RIC recipients were significantly older, with a longer interval from diagnosis to MUD‐SCT and had failed a previous autograft more frequently than CONV recipients. Non‐relapse mortality (NRM) was 24% and 30% at 100‐d and 1‐year, respectively. After a median follow‐up of 36 months, 17% of the patients developed disease progression, the 3‐year progression‐free survival (PFS) being 47%. Three‐year overall survival (OS) for the whole series was 51%. On multivariate analysis, RIC regimens were associated with at lower NRM and a significantly longer PFS and OS. This retrospective study demonstrated that MUD‐SCT results, even in heavily pre‐treated populations, in a meaningful PFS and OS.

Matched unrelated donor stem cell transplant in 131 patients with follicular lymphoma

Matched unrelated donor stem cell transplantation (MUD‐SCT) provides the only curative option for patients with follicular lymphoma (FL) who fail conventional therapies and do not have a sibling donor. The purpose of this study was to analyse the outcome of patients with FL treated with MUD‐SCT included in the European Group for Blood and Marrow Transplantation registry. 131 patients treated with reduced‐intensity conditioning (RIC, n = 87) or conventional myeloablative (CONV, n = 44) MUD‐SCT between 2000 and 2005 were included. Median time from diagnosis to MUD‐SCT was 47 months and the median number of previous therapeutic regimens was 4 (previous autograft: 47%). RIC recipients were significantly older, with a longer interval from diagnosis to MUD‐SCT and had failed a previous autograft more frequently than CONV recipients. Non‐relapse mortality (NRM) was 24% and 30% at 100‐d and 1‐year, respectively. After a median follow‐up of 36 months, 17% of the patients developed disease progression, the 3‐year progression‐free survival (PFS) being 47%. Three‐year overall survival (OS) for the whole series was 51%. On multivariate analysis, RIC regimens were associated with at lower NRM and a significantly longer PFS and OS. This retrospective study demonstrated that MUD‐SCT results, even in heavily pre‐treated populations, in a meaningful PFS and OS.