Publikationsdatum:
2008-11-16
Beschreibung:
Background: Many patients (pts), particularly minorities, lack matched unrelated donors. Mismatched cord blood (CB) transplantation causes less graft versus host disease (GVHD), but is associated with delayed hematopoietic recovery. We studied an alternative donor regimen using T-cell depleted haploidentical stem cells and unrelated CB pioneered by Magro et al. (Haematologica2006;91:640–8) to confirm engraftment with acceptable rates of GVHD. Patients and Methods: We enrolled 15 pts (7 AML, 1 ALL, 2 MDS, 1 CML, 3 NHL, 1 severe aplastic anemia) lacking HLA identical donors. The median age was 28 years (range, 4–66) and median weight was 75 kg (range, 14–124). Twelve pts had active disease at transplant; 2 had prior autologous transplants. Eight pts were Caucasian; 7 other race or ethnicity. The haploidentical donor was the mother in 3; father in 1; child in 4; sibling in 5; and half-sibling in 2 cases. The median haploidentical CD34+ dose was 2.41 × 106/kg (range, 1.25–6.26); CD3+ cells were 0.8 × 104/kg (range, 0.3–1.3). Single unrelated CB units were matched by low resolution at HLA-A and B and high-resolution at DRB1, and matched 6/6 in 1 pt; 5/6 in 7 pts; 4/6 in 6 pts; 3/6 in 1 pt. Median cord total nucleated cells equaled 2.39 × 107/kg (range, 1.07–9.36); CD34+ cells were 0.14 × 106/kg (range, 0.04–0.75). The conditioning regimen for most pts was fludarabine (Flu) (30 mg/m2 × 5 days), thiotepa (5 mg/kg × 2 days), total-body irradiation (TBI) (12 Gy lateral opposed fields), and Thymoglobulin® (rATG) (1.5 mg/kg × 4 days). Five pts unable to tolerate TBI received Flu, melphalan (70 mg/m2 × 2 days), and rATG. GVHD prophylaxis consisted of tacrolimus (Tac) + methylprednisolone or Tac + mycophenolate. Results: Two pts died early (sepsis, CVA). Twelve of the remaining 13 pts engrafted. One pt failed to engraft and died on day (d)36. Median time to ANC 〉500/mL was 9 days (range, 9–12). Median time to sustained platelets 〉20,000/mL was 24 days (range, 12–63). Early haploidentical engraftment was replaced by durable engraftment of CB by 100 days. In unfractionated peripheral blood or bone marrow cells, median haploidentical chimerism was 95% (range, 0–100) on d14; 76% (range, 0–93) on d30; 36% (range, 0–83) on d55; 0% (range, 0–42) on d100; and 0% on d180. Median unfractionated cord chimerism was
Print ISSN:
0006-4971
Digitale ISSN:
1528-0020
Thema:
Biologie
,
Medizin
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