Reduced-intensity conditioning regimen preserves thymic function in the early period after hematopoietic stem cell transplantation

Jiménez, Mónica; Martı́nez, Carmen; Ercilla, Guadalupe; Carreras, Enric; Urbano-Ispizúa, Álvaro; Aymerich, Marta; Villamor, Neus; Amézaga, Núria; Rovira, Montserrat; Fernández‐Avilés, Francesc; Gayà, Anna; Martino, Rodrigo; Sierra, Jorge; Montserrat, Emili

doi:10.1016/j.exphem.2005.06.016

Cited by 42 publications

(37 citation statements)

References 32 publications

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“…Despite the small number of patients studied, more rapid recovery of T cells was observed after RIC-SCT, reaching normal levels of CD3 þ T cells at 6-12 months after transplantation in comparison with 24 months in those patients receiving MAC-SCT. In agreement with these studies, the study by Jimenez et al 26 showed faster recovery of CD3 þ and CD4 þ T cells after RIC-SCT. In this study, a total of 51 consecutive patients undergoing SCT (RIC-SCT n ¼ 24 and MAC-SCT n ¼ 27) were evaluated.…”

Section: Methods Of Analysis Of T-cell Reconstitution After Sctsupporting

confidence: 79%

“…In the study by Jimenez et al, 26 thymopoiesis was evaluated by measuring phenotypically naïve T cells and TREC levels on sorted CD3 þ T cells in the peripheral blood. TRECs are Abbreviations: BM, bone marrow; CSP, cyclosporine A; GVHD, graft versus-host disease; HD CHMT, high dose chemotherapy; MA, myeloablative; MMF, mycophenolate mofetil; MTX, methrotrexate; P, prospective; PBSC, peripheral blood stem cells; R, retrospective; RIC, non myeloablative; TBI, total body irradiation.…”

Section: Thymopoiesis After Ric-sctmentioning

confidence: 99%

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Immune reconstitution after allogeneic stem cell transplantation with reduced-intensity conditioning regimens

2007

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Reduced-intensity conditioning (RIC) regimens have been increasingly used as an alternative to conventional myeloablative conditioning (MAC) regimens for elderly patients, for patients medically infirm to qualify for conventional allogeneic stem cell transplantation (SCT), and for disorders in which traditional MAC-SCT are associated with high rates of nonrelapse mortality. One of the theoretical advantages of RIC-SCT is that it might lend to better immune reconstitution after transplantation due to less damage of the thymus, allowing regeneration of naive T cells derived from prethymic donor stem cells, and due to the proliferation of immunologically competent host T cells that survive the conditioning regimen. Although limited, studies comparing immune recovery following RIC and MAC-SCT have been insightful. One of the main difficulties of these studies is the current spectrum of RIC protocols, which vary considerably in myeloablative and immunosuppressive potential, resulting in apparently contradictory findings. In spite of this, most reports have shown significant quantitative and/or qualitative differences in T-and B-cell reconstitution after RIC-SCT in comparison with conventional SCT. This paper will review current knowledge of immune reconstitution following RIC-SCT.

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Section: Methods Of Analysis Of T-cell Reconstitution After Sctsupporting

confidence: 79%

Section: Thymopoiesis After Ric-sctmentioning

confidence: 99%

Immune reconstitution after allogeneic stem cell transplantation with reduced-intensity conditioning regimens

2007

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“…31 On the other hand, higher post transplant CD4 þ 45RA þ levels were observed in the early period after RIC when compared to myeloablative HSCT. 32 Other authors found a superior immunity in non-myeloablative HSCT recipients early after transplantation, whereas counts of total and naive CD4 þ T cells were higher in myeloablative patients after 1 year. 33 These different observations in immune reconstitution after RIC are probably due to the variability of the used protocols as well as the variable use of ATG or immunosuppressants in several investigations concerning this issue.…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients

Heining

Spyridonidis

Bernhardt

et al. 2007

Bone Marrow Transplant

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Here we investigated the influence of parameters known before hematopoietic stem cell transplantation (HSCT) as well as the relevance of graft-versus-host disease (GvHD) and cytomegalovirus (CMV) reactivation on post transplant lymphocyte reconstitution in 148 patients treated in our institution between 1996 and 2003. Median patient age was 42 (19-68) years, HSCT followed standard high dose (n ¼ 91) or reduced-intensity conditioning regimens (n ¼ 57) with bone marrow (BM, n ¼ 67) or peripheral blood stem cells (PBSC, n ¼ 81) from related (n ¼ 71) or unrelated (n ¼ 77) donors. In the first months, we observed a partially faster reconstitution of CD3 þ 4 þ , CD3 þ 8 þ and CD4 þ 45RA þ T cells in patients following peripheral blood stem cell transplantation when compared to bone marrow transplantation. Prolonged CD3 þ 4 þ and CD4 þ 45RA þ lymphopenia was noted after unrelated donor HSCT and GvHD prophylaxis containing anti-T-lymphocyte globulin. Lymphocyte subset counts in patients older than the median age were comparable to those in patients transplanted at a younger age and not influenced by the conditioning regimen. CD3 þ 8 þ T cell reconstitution was strongly correlated with CMV reactivation, but not significantly affected by CMV serostatus before HSCT. Incidence or extent of GvHD did not significantly influence lymphocyte reconstitution. Therefore, the source of graft is the most predictive parameter in early lymphocyte reconstitution, but the differences in lymphocyte recovery completely resolved within the first year after HSCT.

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“…1 Reduced intensity conditioning (RIC) regimens may be associated with more rapid immunologic reconstitution than myeloablative conditioning via mechanisms such as the preservation of T-celldependent mitogenic responses 2 , thymic function 3 and increased early T-cell repertoire complexity. 4 Other studies have not demonstrated significantly improved immune reconstitution with RIC, 5,6 making this area a subject of continued debate (reviewed by Jimenez et al 7 ).…”

Section: Introductionmentioning

confidence: 99%

Impact of lymphocyte and monocyte recovery on the outcomes of allogeneic hematopoietic SCT with fludarabine and melphalan conditioning

DeCook

Thoma

Huneke

et al. 2012

Bone Marrow Transplant

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We have recently shown that lymphocyte and monocyte recovery by day þ 100 are associated with survival post myeloablative allogeneic hematopoietic transplant for acute leukemia. We hypothesized that lymphocyte and monocyte recovery would have a similar impact on survival in the reduced intensity setting. To test this hypothesis, we analyzed clinical data from 118 consecutive fludarabine/melphalan-conditioned patients by correlating peripheral blood absolute lymphocyte counts and monocyte counts (ALC and AMC, respectively) at days þ 15, þ 30, þ 60 and þ 100 with the outcomes. Multivariate analysis revealed that day þ 100 AMC (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.07-0.73, P ¼ 0.01) and mild chronic GVHD (RR 0.09, 95% CI 0.005-0.43, P ¼ 0.008) were independently associated with survival. To explore whether the patterns of lymphocyte and monocyte recovery had a prognostic value, we performed unsupervised hierarchical clustering on the studied hematopoietic parameters and identified three patient clusters, A-C. Patient clusters A and B both had improved OS compared with cluster C (77.8 months vs not reached vs 22.3 months, respectively, Po0.001). No patient in cluster C had a day þ 100 AMC 4300. Both severe acute GVHD and relapse occurred more frequently in cluster C. Our data suggest that patients with low AMC by day þ 100 post fludarabine/melphalanconditioned allogeneic hematopoietic SCT may be at risk for poor outcomes.

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Reduced-intensity conditioning regimen preserves thymic function in the early period after hematopoietic stem cell transplantation

Cited by 42 publications

References 32 publications

Immune reconstitution after allogeneic stem cell transplantation with reduced-intensity conditioning regimens

Immune reconstitution after allogeneic stem cell transplantation with reduced-intensity conditioning regimens

Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients

Impact of lymphocyte and monocyte recovery on the outcomes of allogeneic hematopoietic SCT with fludarabine and melphalan conditioning

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