Haploidentical allogeneic hematopoietic cell transplantation in adults with reduced-intensity conditioning and CD3/CD19 depletion: fast engraftment and low toxicity.
OBJECTIVE
CD3/CD19 depletion may improve engraftment and immune reconstitution after haploidentical hematopoietic cell transplantation (HHCT) as grafts not only contain CD34+ stem cells but also CD34- progenitors and natural killer, dendritic, and facilitating cells.


METHODS
Ten consecutive patients received HHCT with CD3/CD19-depleted grafts. Reduced-intensity conditioning was performed with fludarabine (150-200 mg/m2), thiotepa (10 mg/kg), melphalan (120 mg/m2), and OKT-3 (5 mg/day, day -5 to +14) without additional posttransplant immunosuppression. Diagnoses were AML (n = 4), ALL (n = 3), NHL (n = 2), and multiple myeloma (n = 1). All patients were "high risk" with refractory disease or relapse after preceding HCT. The CD3/CD19-depleted haploidentical grafts contained a median of 7.8 x 10(6) (range, 5.2-17 x 10(6)) CD34+ cells/kg, 5.5 x 10(7) (range, 0.02-8.6 x 10(7)) CD56+ cells/kg, and 2.0 x 10(4) (range, 0.006-44 x 10(4)) CD3+ T cells/kg. Engraftment was rapid with median time to greater than 500 granulocytes/microL of 13 (range, 11-17) days, greater than 20,000 platelets/microL of 11 (range, 8-16) days, and full donor chimerism after 2 weeks in all patients. Six cases of grade II GVHD occurred. One patient, who received the highest T cell dose, developed lethal grade IV GVHD. Treatment-related mortality in the first 100 days was 3/10 (30%) with one death each due to idiopathic pneumonia syndrome, GVHD, and CMV disease. Two patients died after day 100, one due to relapse and one with systemic adenoviral infection. Overall survival is 5/10 patients (50%) with a median follow-up of 435 (range, 229-814) days.


CONCLUSIONS
This regimen is promising in high-risk patients lacking a suitable donor, and a prospective phase I/II study is ongoing.
Bethge
Wolfgang A
WA
Medical Center, University of Tuebingen, Tuebingen, Germany. wolfgang.bethge@med.uni-tuebingen.de
Haegele
Matthias
M
Faul
Christoph
C
Lang
Peter
P
Schumm
Michael
M
Bornhauser
Martin
M
Handgretinger
Rupert
R
Kanz
Lothar
L
D000328:Adult; D018941:Antigens, CD19 / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology / Q000628:therapy; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D018941:Antigens, CD19; D017252:CD3 Complex