Immune reconstitution after haematopoietic cell transplantation in children: immunophenotype analysis with regard to factors affecting the speed of recovery

Summary:We retrospectively analyzed data on T-and B-cell reconstitution and infectious complications in 58 children undergoing ABMT, in order to evaluate post-transplant supportive care measures used during the study period. Normalization of T-cell number and lymphocyte proliferative responses to phytohemagglutinin (PHA) and alloantigen (MLC) occurred in two-thirds of children by 6 months post transplant. Normal IgM levels developed in 75% of children by 6 months post transplant. A total of 34 children (59%) developed 39 episodes of infection between neutrophil engraftment and 1 year post transplant. The most common infections included bacteremia, varicellazoster virus infection and pneumonia, which represented 46, 23 and 9% of infections, respectively. All patients with bacteremia had a central venous catheter in place at the time of infection. Most infections (77%) developed by 6 months post transplant. In this small patient cohort, time to normalization of tests of T-and B-cell function was not significantly different between patients with and without infection. Earlier removal of an indwelling central venous catheter may decrease the risk of bacteremia post transplant. Post-transplant supportive care measures may be discontinued at 6 months post ABMT in most children, as the risk of infection decreases after that time.

Section: Immune Reconstitutionsupporting

confidence: 89%

Section: Transplantmentioning

confidence: 99%

Immune reconstitution, infectious complications and post transplant supportive care measures after autologous blood and marrow transplantation in children

Machatschek

Duda

Matthay

et al. 2003

“…29,30 It is known that T-and B-cell recovery in peripheral blood occurs later in children receiving alemtuzumab than in those who receive ATG. 31 Also, transplantation of PBSC in children seemed to elicit the fastest reconstitution of CD3 þ , CD4 þ CD3 þ , CD8 þ CD3 þ and naı¨ve T-cells compared with BM or CD34-selected PBSC, which did not differ.…”

Section: Discussionmentioning

confidence: 99%

A pilot study of reduced toxicity conditioning with BU, fludarabine and alemtuzumab before the allogeneic hematopoietic SCT in children and adolescents

Styczyński

Tallamy

Waxman

et al. 2010

We report the results of a pilot study of a BU-fludarabinealemtuzumab (BFA)-reduced toxicity conditioning (RTC) followed by allogeneic hematopoietic SCT (AlloHSCT) in 12 children and adolescents (o21 years) with malignant and non-malignant diseases. Stem cell sources were: two unrelated cord blood, one unrelated BM, two related and seven unrelated PBSC. Positive CD34 selection was performed in five unrelated PBSC grafts. RCT was carried out with BFA, and GVHD prophylaxis was FK506 and mycophenolate mofetil. The median time for neutrophil and platelet engraftment was 16 and 31 days, respectively. The P of developing Xgrade II, Xgrade III aGVHD and cGVHD was 41.6, 25 and 9%, respectively. Only 1 out of 12 developed Xgrade III toxicity. There was one primary and no secondary graft failure. Mixed donor chimerism on day 100 and 1 year was median 99 and 96%, respectively; X90% of recipients achieved X80% donor chimerism. The 3-year overall survival (OS) in all patients was 91.7 ± 8% (100% for malignant vs 80% for non-malignant diseases, ns). In all, 11 (91%) patients remain alive at median 2.8 (0.3-6.8) years. RTC followed by AlloHSCT, based on BFA conditioning, is feasible and tolerable in children and adolescents, and results in prompt achievement of durable mixed donor chimerism and excellent OS.

“…A number of factors influence the haematopoietic reconstitution after SCT, such as the graft source, 5 the immunosuppressive therapy and the age of the patients. 6 SCT with full peripheral blood stem cell (PBSC) grafts results in an earlier immune reconstitution compared to bone marrow (BM) grafts, whereas CD34-selected (PBSC-CD34 þ ) grafts elicit a haematopoietic recovery similar to BM. 5,7 The differences are attributed to the number of lymphocytes transfused with the grafts.…”

Section: Introductionmentioning

confidence: 99%

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

Koehl

Bochennek

Zimmermann

et al. 2007

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.