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Double-Unit Cord Blood (CB) Transplantation Combined with Haplo-Identical CD34+ Cells Results in 100% CB Engraftment with Enhanced Myeloid Recovery
Background: Double-unit CB transplantation (DCBT) has provided high rates of sustained donor engraftment. However, delayed engraftment is frequent & is associated with increased transplant-related mortality (TRM). Methods: We investigated the combined transplantation of a 4-6/6 double-unit CB allograft (infused day 0) with peripheral blood derived Miltenyi CD34+ selected haplo-identical stem cells (haplo-CD34+, infused day 0 or +1) to speed myeloid recovery. DCB grafts were used to facilitate comparison with DCB only controls. Results: Of 23 eligible patients, 6/23 (26%) had no suitable haplo-identical donor. Thus, 17 patients (median 39 years, range 16-69) were transplanted 9/2012-6/2013 with DCB plus haplo-CD34+ cells for high-risk hematologic malignancies. Conditioning was myeloablative with CSA/MMF immunosuppression. Median infused CB TNC x 107/kg was 2.29 (larger unit) & 1.82 (smaller unit). 15 patients received 3 x 106/kg CD34+ cells (the targeted dose) whereas 2 each received 1 x 106/kg. The median infused haplo-CD3+ dose was 0.6 x 103/kg (range 0.3-1.6). One patient died on day 14. Of 16 evaluable patients, all (100%) engrafted. The median neutrophil recovery was 13.5 days (range 11-31) in 14 patients who received 3 x 106/kg haplo-CD34+ cells, & 26 & 18 days in 2 patients who received 1 x 106/kg haplo-CD34+ cells. Platelet recovery occurred in 13/16 patients (median 26 days, range 17-46). While day 14 myeloid recovery was predominantly haplo-mediated, one CB unit dominated by day 28 in both neutrophil & T-cell subsets (Table). By day 60, the median total donor chimerism was 100% the dominant CB unit. With a median survivor follow-up of 7 months (range 3-12), 12/16 patients developed gr. II-IV aGVHD by day 100 (10 gr. II, 1 gr. III, 1 gr. IV). One refractory leukemia patient relapsed & 5 had TRM (3 organ failure, 1 grade IV aGVHD, 1 CMV infection). Surviving patients were discharged at a 33 day median (9 days faster than DCBT controls). Conclusions: Double-unit CBT with haplo-CD34+ cells is safe & neutrophil engraftment is enhanced. A shorter initial hospitalization offsets the haplo-CD34+ cell cost. It is intriguing that the dominant CB unit can rapidly reject the haplo-identical donor. Whether the same results could be achieved with single CB units, and whether myeloid recovery could be further enhanced by a higher haplo-CD34+ cell dose, require investigation.
Donor | Serial Peripheral Blood (PB) Chimerism*, Median (Range) | ||||
Day +14 Whole PB (n = 15) | Day +28 PB Subsets (n = 15) | Day +60 Whole PB (n = 13) | Day +100 PB Subsets (n = 13) | Day +180 Whole PB (n = 9) | |
Dominant CB Unit | 17% (0-100) | Neut: 85% (0-100) T: 100% (0-100) | 100% (34-100) | Neut:100% (77-100) T: 100% (50-100) | 100% (all 100) |
Non- Engrafting CB Unit | 0% (0-11) | Neut: 0% (0-22) T: 0% (0-100) | 0% (0-25) | Neut: 0% (0-20) T: 0% (0-50) | 0% |
Haplo- Donor | 77% (0-100) | Neut: 0% (0-100) T: 0% (0-19) | 0% (0-66) | Neut: 0% (0-23) T: 0% (0-1) | 0% |
* Patient with early relapse is excluded.
SOBI, none: Research Funding
Bioline, Consultant: Advisory Board, Consultancy and Honoraria
Janssen, Consultant: Advisory Board, Consultancy and Honoraria
Onyx, Consultant: Advisory Board, Consultancy and Honoraria
Sanofi, Consultant: Advisory Board, Consultancy and Honoraria
Seattle Genetics, Consultant: Advisory Board, Consultancy and Honoraria
Skyline Diagnostics, Consultant: Advisory Board, Consultancy and Honoraria
Spectrum Pharmaceuticals, Consultant: Advisory Board, Consultancy and Honoraria
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