Immune reconstitution at 6 months following t-cell depleted hematopoietic stem cell transplantation is predictive for treatment outcome

Novitzky, Nicolás; Davison, Glenda Mary; Hale, Geoff; Waldmann, Herman

doi:10.1097/00007890-200212150-00012

Cited by 51 publications

(33 citation statements)

References 29 publications

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“…Although our results are limited by the relatively small sample size of the groups, our data indicate a minimum number of cytotoxic T cells needs be reached within a certain period of SCT. Novitzky et al 35 described similar to our paediatric patients, in 42 adult patients, that treatment failure was associated with low total CD8 þ cells, when tested at 6 months post SCT. The high importance of CD8 þ cells after SCT is confirmed by clinical reports where a higher relapse rate was observed in patients with lower CD8 þ and NK cells, whereas blood levels of the CD4 þ populations were not associated with outcome.…”

Section: Discussionsupporting

confidence: 82%

Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8+CD3+ count reconstitution is associated with survival

Koehl

Bochennek

Zimmermann

et al. 2007

Bone Marrow Transplant

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To evaluate the correlation between kinetics of immune reconstitution and survival, we prospectively evaluated lymphocyte subsets in 32 paediatric patients undergoing allogeneic stem cell transplantation (SCT) for haematological malignancies. Four-colour flow cytometric analysis was performed at short intervals with a median follow-up of 4 years post SCT. A total of 50% of patients reached age-matched 5th percentile of natural killer, cytotoxic T, B and helper T cells 4, 9, 20 and 28 weeks after SCT, respectively, which increased to more than 80% within 1 year after SCT. Transplantation of peripheral blood stem cells (PBSC) seemed to elicit the fastest reconstitution of CD3 þ , CD4 þ CD3 þ , CD8 þ CD3 þ and naı¨ve T cells compared to bone marrow (BM) or CD34-selected PBSC, which did not differ. Most importantly, we observed a significantly higher number of survivors among patients whose CD8 þ CD3 þ absolute counts rose above the 5th percentile of age-matched normal levels during the first year post SCT compared to patients who never reached these levels (19/25 vs 0/7, Po0.001). This was still present in both subgroups, BM-and CD34-selected grafts (P ¼ 0.03, 0.02). These results from a small patient sample underline the importance of particular lymphocyte subsets for the outcome of children undergoing SCT. A larger study with detailed subset analysis is underway.

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Section: Discussionsupporting

confidence: 82%

Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8+CD3+ count reconstitution is associated with survival

Koehl

Bochennek

Zimmermann

et al. 2007

Bone Marrow Transplant

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“…Recently, published studies suggest that rapid T cell reconstitution may correlate positively with overall survival after allogeneic hematopoietic stem cell transplantation (alloHSCT). 3,4 For these reasons, restoration of the immune system following alloHSCT remains a focus of ongoing research.…”

Section: Introductionmentioning

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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“…Low TLC at 1 month post transplant is predictive for relapse in acute myeloblastic leukaemia (AML) and acute lymphoblastic leukaemia (ALL). [6][7][8] Lower TLC at 6 months is predictive of treatment failure (relapse, death or graft failure) following T-cell-depleted allo-SCT, 9 and lower TLC has also been identified as a risk factor for progressive adenovirus and death after RIC with alemtuzumab. 10 In this study, we compared the post transplant recovery of TLC in patients receiving RIC with in vivo alemtuzumab to those receiving T-cell-replete MAC.…”

mentioning

confidence: 99%

Similar lymphocyte recovery and CMV reactivation profiles between reduced intensity conditioning with alemtuzumab and myeloablative allogeneic stem cell transplantation

Hill

Collyns

et al. 2008

Bone Marrow Transplant

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Immune reconstitution at 6 months following t-cell depleted hematopoietic stem cell transplantation is predictive for treatment outcome

Abstract: After T-cell depleted allogeneic PBPC or BMT, no differences in the rate of immune recovery were detected. However, patients with specific subset abnormalities at 6 months from grafting had a significantly higher risk of treatment failure.

Cited by 51 publications

References 29 publications

Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8+CD3+ count reconstitution is associated with survival

Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8+CD3+ count reconstitution is associated with survival

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

Similar lymphocyte recovery and CMV reactivation profiles between reduced intensity conditioning with alemtuzumab and myeloablative allogeneic stem cell transplantation

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