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Early engraftment and full-donor chimerism after single-cord blood plus third-party donor dual transplantation in patients with high-risk acute leukemia

Bone Marrow Transplantation volume 49, pages 145–147 (2014)Cite this article

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Umbilical cord blood (UCB) has emerged as a safe and effective hematopoietic cell (HC) source for adult acute leukemia patients who lack an HLA-matched donor.1 While UCB transplants offer advantages compared with other allogeneic HC sources, their hematopoietic engraftment and immune reconstitution are delayed and limited by the number of HCs contained in the UCB unit together with donor-recipient HLA disparities.2 A dual transplant strategy combining UCB plus third-party donor (TPD) HC (UCB–TPD) pioneered at Hospital Puerta de Hierro in Madrid has been shown to improve early outcomes after UCB transplantation by hastening hematopoietic recovery.3 Here, we present an independent series of 13 consecutive high-risk myelodysplastic syndrome (MDS)/AML and ALL patients, median age 45 years (20–64) and weight 71 Kg (56–104), who received a myeloablative UCB–TPD dual transplant in our center from February 2009 to January 2013. Patients lacked a matched related or unrelated donor, were in advanced stage and heavily pretreated: seven refractory to ⩾1 line of chemotherapy, three relapsed after a previous HC transplant, and two had active AML (9 and 22% blasts) prior to UCB–TPD transplant (Table 1). Our non-TBI chemotherapy-based myeloablative4 conditioning and GVHD prophylaxis regimen included BU (12 mg/kg), CY (100 mg/kg), fludarabine (120 mg/m2), thymoglobulin (4 mg/kg), CsA and a short course of methylprednisolone. Patients received UCB units with 1–3 out of 6 HLA mismatches (A, B antigenic; DR allelic), a median post-thawing total nucleated cell count of 2.62 × 107/kg (1.39–5.8) and CD34+ cell count of 0.98 × 105/kg (0.35–2.26),5 followed by a median 4.96 × 106/kg miltenyi-purified TPD CD34+ cells (3.62–11.90) with <1 × 104/kg CD3+ cells (Table 2). TPD were haploidentical relatives in all cases but one, patient no. 9, whose TPD was a fully mismatched brother. G-CSF (30MU) was administered from day +1 until sustained neutrophil engraftment >1 × 109/L.

Table 1 Patient demographics, disease characteristics and clinical follow-up
Full size table
Table 2 Characteristics of cellular products and kinetics of donor chimerism
Full size table

All patients engrafted neutrophils >0.5 × 109/L and platelets >20 × 109/L by median days +12 (range, 10–17) and +23 (range, 12–105), respectively. Twelve cases (92%) achieved full-donor chimerism as early as 2 weeks after UCB–TPD transplant. Donor chimerism and engraftment were initially derived from the TPD in all cases, and shifted rapidly to UCB in all evaluable patients but one, case no. 10, whose post-thawing UCB viability and cell counts (Table 2) were low, failing to engraft the CBU and remaining in CR and sustained haploidentical donor chimerism until his most recent follow-up, 15 months after transplant.

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Authors and Affiliations

  1. Department of Haematology, Catalan Institute of Oncology (ICO)—Hospital Duran i Reynals, Barcelona, Spain

    I Sánchez-Ortega, M Arnan, B Patiño & R F Duarte

  2. Group of Hematological Malignancies, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain

    I Sánchez-Ortega, M Arnan, B Patiño & R F Duarte

  3. Laboratori d'Immunobiologia per a la Reçerca i Aplicacions Diagnòstiques (LIRAD), Banc de Sang i Teixits, Barcelona, Spain

    M J Herrero

  4. Cell Therapy Unit and Cord Blood Bank, Banc de Sang i Teixits, Barcelona, Spain

    S Querol

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  1. I Sánchez-Ortega
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Correspondence to R F Duarte.

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Sánchez-Ortega, I., Arnan, M., Patiño, B. et al. Early engraftment and full-donor chimerism after single-cord blood plus third-party donor dual transplantation in patients with high-risk acute leukemia. Bone Marrow Transplant 49, 145–147 (2014). https://doi.org/10.1038/bmt.2013.113

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