Rapid recovery of lymphocyte subsets is not associated with protection from relapse of myelodysplastic syndromes and acute myeloid leukaemia after haematopoietic stem cell transplantation using a reduced intensity conditioning regimen and alemtuzumab.

Graft-versus-leukaemia (GvL) and graft-versus-host disease (GvHD) are both caused by alloreactive lymphocytes. We previously reported that GvHD correlated with higher numbers of effector CD4 T cells and Natural Killer cells early after allogeneic transplantation using a regimen comprising fludarabine, busulphan and alemtuzumab. Here, we assessed immune cell subset recovery in these patients in the context of early myeloid malignant disease relapse. Despite the close relationship between the GvL and GvHD immune responses, rapid recovery of lymphocyte subsets was not associated with protection from disease relapse. These results indicated that GvL may be weak in this treatment setting for patients with myelodysplastic syndromes and acute myeloid leukaemia. Consistent with low GvL activity, we previously reported that mixed T cell chimaerism had no detrimental effect on relapse in this treatment setting and instead correlated with better outcome because of reduced GvHD incidence. We now report that patients with significantly higher lymphocyte numbers prior to transplantation subsequently maintained the mixed T cell chimaeric state. This pre-transplant profile, together with absence of the early post-transplant signature indicative of GvHD predisposition, could potentially be used to identify patients suitable for early withdrawal of immunosuppression and prophylactic donor leucocyte infusion to boost GvL activity.

The outcome of unrelated donor stem cell transplantation for patients with multiple myeloma.

We performed a retrospective analysis of outcome in 45 patients with multiple myeloma receiving unrelated donor stem cell transplants (UD-SCT) in the UK between 1993 and 2002; 17 received myeloablative conditioning regimens and 28 received reduced intensity conditioning (RIC) protocols. Forty patients received pretransplant CAMPATH serotherapy. Forty-two of 45 patients had detectable disease at transplant, but 33 of 45 were chemoresponsive. Sixty per cent of patients had received a previous autograft. Myeloid engraftment was seen in 95% of recipients and was significantly faster in recipients receiving peripheral blood stem cells (P = 0.07) and RIC (P = 0.001). The incidence of severe (grade 3/4) acute graft versus host disease (aGvHD) was 5% (2/40). The 100-d non-relapse mortality was 18% (5/38) following RIC and 53% (9/17) following myeloablative regimens. Twenty-nine per cent of patients achieved a complete remission, 61% a partial remission, giving a 90% overall response rate. At median follow-up (513 d), overall survival was 40%: 54% in the RIC group (median follow-up: 489 d) and 18% in the myeloablative group (median follow-up: 560 d). In recipients of UD-SCT, RIC protocols that incorporated CAMPATH were associated with faster myeloid engraftment, less severe aGvHD and lower 100-d non-relapse mortality than myeloablative regimens, without a corresponding rise in relapse rate during the period of observation.

Receptores de células asesinas naturales: relevancia funcional / Natural killer cell receptors: functional roles

El Sistema inmune adaptativo, con sus receptores inmunoglobulínicos y receptores de células T, ha cautivado el enfoque de la mayor parte de la investigación inmunológica y opacado la importancia de los receptores expresados por células del sistema inmune innato. Las células Asesinas Naturales (NK) han desarrollado dos sistemas de receptores principales para llevar a cabo su función, ambos sistemas emplean receptores tanto inhibitorios como activatorios, e incluyen a miembros de la Superfamilia Inmunoglobulina-similes al igual que Receptores Lectina tipo C-símiles. Los receptores Inmunoglobulina-símiles KIR son receptores polimórficos de superficie celular capaces de reconocer a molécluas clásicas de HLA de clase I y modular de manera alternativa la repsuesta inmune a células infectadas o tumorales. Los receptores Lectina-símiles recientemente han demostrado poseer la capacidad de reconocer a moléculas no-clásicas del Complejo Mayor de Histocompatibilidad (MHC) tales como HLA-E y la cadena relacionada a clase I de MHC (MICA). La extensión de la diversidad y de la complejidad organisacional que estos receptores geneticamente pre-establecidos y no-rearreglantes poseen, ha sido recientmente demostrada. Los receptores de células NK se han visto implicados en una gran variedad de escenarios clínicos incluyendo a la resistencia/susceptibilidad a infecciones por patógenos, el reconocimiento, eliminación y vigilancia antitumoral, al igual que como elementos importantes para el desenlace del transplante de organos sólidos y de células hematopoyéticas. Las relaciones funcionales que existen entre el MHC y los receptores de células NK nos brindan una mejor comprension de la respuesta inmune a incursiones patogénicas, neoplasias asi como en la transplantación clínica (AU)