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Partial depletion of TCR alpha/beta+/ CD19+ cells in matched unrelated transplantation of three patients with osteopetrosis

Bone Marrow Transplantation volume 50, pages 1583–1585 (2015)Cite this article

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Hematopoietic stem cell transplantation (HSCT) represents a commonly employed and effective therapy for children affected by severe onco-hematological diseases. When a familial identical donor is not available, transplant with a matched unrelated donor (MUD) is the treatment of choice.1 The major concern, in this setting, is the incidence and severity of GvHD, both acute (aGvHD) and chronic (cGvHD). For instance, previous data obtained in 54 MUD-transplanted children with SCID followed in our institution and in a Canadian pediatric referral center for primary immunodeficiency, demonstrated that 16% of patients developed aGvHD of grade III–IV, while 15% presented with cGvHD.2 In MUD-transplanted patients, the mortality, which is 10%–40% at day +100, is highly correlated with aGvHD, type of disease, donor and stem cell source, conditioning and GvHD prophylaxis.3, 4 As reported by Pai et al.,5 the use of T-cell depleted PBSC reduces GvHD in transplants with non HLA-identical donor, and several techniques have been used for T-cell depletion. Regulatory T cells have been also used to suppress GvHD without loss of graft-versus-leukemia (GVL) activity.6 In addition, the adoptive transfer and in vivo expansion of haploidentical TCR gamma/delta+ T lymphocytes has a potential role in the treatment of hematological diseases by enhancing engraftment without inducing GvHD.7 While there is no clear association between T-cell dose and incidence or severity of GvHD, it is known that the presence in the graft of a minimal T-cell dose is required to exert both graft versus tumor (GVT) and GvHD responses.8 Indeed, in a consecutive series of 22 MUD transplants, we have previously found that the incidence of aGvHD of grade III–IV can be reduced to 9% if the number of infused donor T cells did not exceed 20–70 × 106 T cells/kg (Porta F, personal communication). Therefore, in order to improve engraftment and to avoid or decrease intensity and severity of aGvHD, in this pilot study we combined the last two approaches in three patients with infantile malignant osteopetrosis (IMO) candidate to MUD transplant.

IMO is a rare genetic condition in which the increase of bone mass is caused by defects in osteoclast formation and function. A study, performed in our institution in 14 patients who received a total of 18 HSCT indicated that event-free survival (that included death, graft failure, loss of engraftment, severe infections, aGvHD of grade ⩾III and cGvHD) was 80% after HSCT with matched sibling donors, 27.8% with MUD and 0% with mismatched related donor.9 Furthermore, Driessen et al.10 found that the 5-year disease-free survival in MUD-transplanted IMO patients was 40%, while an international survey performed in 125 patients demonstrated that it was 88% after transplants with matched sibling donor, 80% after MUD and 66% after haploidentical transplants.11 The major problem in children affected by IMO undergoing HSCT with MUD is late transplant failure9 and, according to our own experience, only 50% of children achieved a sustained engraftment (Porta F, personal communication).

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Authors and Affiliations

  1. Oncohaematology and Bone Marrow Transplantation Unit, Children’s Hospital, Brescia, Italy

    F Porta & S Cavagnini

  2. Diagnostics Department, Centro Ricerca Emato-oncologica AIL (CREA), Spedali Civili of Brescia, Brescia, Italy

    L Imberti & A Sottini

  3. Section of Haematology and Coagulation, Stem Cell Lab, Spedali Civili of Brescia, Brescia, Italy

    F Bolda, A Beghin, A Caruso & A Lanfranchi

  4. Department of Molecular and Translational Medicine, Section of Microbiology, University of Brescia, Brescia, Italy

    A Caruso

Authors
  1. F Porta
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  2. S Cavagnini
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  3. L Imberti
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  4. A Sottini
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  5. F Bolda
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  7. A Caruso
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  8. A Lanfranchi
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Correspondence to F Porta.

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Porta, F., Cavagnini, S., Imberti, L. et al. Partial depletion of TCR alpha/beta+/ CD19+ cells in matched unrelated transplantation of three patients with osteopetrosis. Bone Marrow Transplant 50, 1583–1585 (2015). https://doi.org/10.1038/bmt.2015.201

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