Impact of fetal-maternal tolerance in hematopoietic stem cell transplantation

Teshima, Takanori; Matsuoka, Ken; Ichinohe, Tatsuo

doi:10.1007/s00005-006-0018-y

Cited by 17 publications

(7 citation statements)

References 89 publications

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“…Recent data support a mechanism of long-lasting Treg-mediated tolerance of maternal cells by offspring. 39 Whereas child-to-mother transplantations have been associated with superior outcomes in other transplantation settings, 40 in our limited population, they were associated with higher rates of relapse. It is possible that the outcomes associated with this donor-recipient combination are dependent on the particular disease state and transplantation regimen, which together will determine whether an increase or decrease in alloreactivity is likely to be beneficial or detrimental.…”

Section: Discussionmentioning

confidence: 74%

A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing

Grosso

Carabasi

Filicko-O'Hara

et al. 2011

Blood

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Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 ؋ 10 8 /kg of T cells resulted in consistent engraftment, immune reconstitution, and acceptable rates of GVHD. Cumulative incidences of grade III-IV GVHD, nonrelapse mortality (NRM), and relapse-related mortality were 7.4%, 22.2%, and 29.6%, respectively. With a follow-up of 28-56 months, the 3-year probability of overall survival for the whole cohort is 48% and 75% in patients without disease at HSCT. In the context of CY tolerization, a high, fixed dose of haploidentical T cells was associated with encouraging outcomes, especially in good-risk patients, and can serve as the basis for further exploration and optimization of this 2-step approach. This study is registered at www.clinicaltrials.gov as NCT00429143. (Blood. 2011;118(17): 4732-4739) IntroductionUntil recently, HLA haploidentical hematopoietic stem cell transplantation (HSCT) has often been associated with disappointing clinical outcomes, limiting the widespread application of this approach. Higher rates of infection and relapse, 2 consequences of the T-cell depletion required to prevent severe GVHD in recipients of HLA mismatched grafts, adversely affect long-term survival, particularly in patients receiving HSCT late in their disease course. Because only a subset of appropriate transplantation candidates has an HLA-identical sibling or unrelated donor, the development of safer, more efficacious transplantation approaches using haploidentical donors would provide potential transplantation options for patients who lack well-matched donors.Based on murine models, clinical approaches to haploidentical transplantation initially relied on aggressive T-cell depletion techniques. Ex vivo T-cell depletion with soybean agglutinin and E rosetting or the use of mAbs such as T10B9 resulted in BM products containing T-cell doses in the range of 10 4 -10 5 T cells/kg of recipient body weight. This degree of T-cell depletion was associated with the attenuation of severe GVHD and provided consistent engraftment, particularly when antithymocyte globulin was also administered. 1,2 The correlate of a high degree of T-cell depletion to avoid GVHD is delayed posttransplantation immune recovery, 3-9 mortality from infection and relapse, 1,10-16 and higher rates of graft rejection compared with T cell-containing regimens. 17 Ruggeri et al 18 demonstrated that the higher relapse rates associated with T-cell depletion can be moderated in part b...

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Section: Discussionmentioning

confidence: 74%

A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing

Grosso

Carabasi

Filicko-O'Hara

et al. 2011

Blood

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“…2 We have previously reported constitutively active nuclear factor-B signaling in ENKL. 3 Here, we report that this earlier finding has given us a promising lead for NK-cell neoplasm treatment. Bortezomib, the proteasome inhibitor, targets nuclear factor-B activation and can be used to treat multiple myeloma and mantle-cell lymphoma.…”

Section: Proteasome Inhibitor Bortezomib-induced Apoptosis In Naturalmentioning

confidence: 73%

Role of primacy of birth in HLA-identical sibling transplantation

Bucher¹,

Stangel²,

Buser³

et al. 2007

Blood

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“…There are many studies suggesting that NIMA but not NIPA may influence alloresponses in humans. A study on the impact of feto‐maternal tolerance in haematopoietic stem cell transplantation showed that NIMA‐specific tolerance was maintained by an immunological mechanism (Teshima et al ., 2006). Female cells were detected in multiple tissues when studying four male infants who had never received a blood transfusion as they died during the first week of life.…”

Section: Discussionmentioning

confidence: 99%

The non‐inherited maternal HLA haplotype affects the risk for type 1 diabetes

Åkesson

Carlsson

Ivarsson

et al. 2009

Int J Immunogenetics

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The aim was to test the hypothesis that the human leucocyte antigen (HLA) haplotype that is not inherited from the mother, that is, the non-inherited maternal antigen (NIMA) affects the risk for type 1 diabetes (T1D). A total of 563 children with T1D and 286 non-diabetic control children from Sweden were genotyped for DRB1, DQA1 and DQB1 alleles. The frequency of positively (DR4-DQA1*0301-B1*0302 and DR3-DQA1*0501-B1*0201), negatively (DR15-DQ A1*0102-B1*0602) or neutrally (all other) T1D associated HLA haplotypes were compared between NIMA and non-inherited paternal antigen (NIPA). All comparisons were carried out between HLA-matched patients and controls. The frequency of positively associated NIMA was higher among both DR4/X-positive healthy individuals compared wit DR4/X-positive patients (P < 0.00003) and DR3/X-positive healthy individuals compared with DR3/X-positive patients (P < 0.009). No such difference was observed for NIPA. High-risk NIMA was increased compared to NIPA among healthy DR3/X- and DR4/X-positive children (P < 0.05). There was no difference in frequency of positively associated haplotypes between patient NIMA and NIPA. The NIMA but not the NIPA affects the risk for T1D, suggesting that not only the inherited but also non-inherited maternal HLA haplotypes, perhaps through microchimerism or other mechanisms, may influence the risk for the disease.

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Impact of fetal-maternal tolerance in hematopoietic stem cell transplantation

Cited by 17 publications

References 89 publications

A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing

A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing

Role of primacy of birth in HLA-identical sibling transplantation

The non‐inherited maternal HLA haplotype affects the risk for type 1 diabetes

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