scholarly journals Reduced-Intensity Conditioning with Fludarabine, Cyclophosphamide, and High-Dose Rituximab for Allogeneic Hematopoietic Cell Transplantation for Follicular Lymphoma: A Phase Two Multicenter Trial from the Blood and Marrow Transplant Clinical Trials Network

2016 ◽  
Vol 22 (8) ◽  
pp. 1440-1448 ◽  
Author(s):  
Ginna G. Laport ◽  
Juan Wu ◽  
Brent Logan ◽  
Veronika Bachanova ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Multicenter Trial ◽  
Marrow Transplant ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
Blood And Marrow Transplant ◽  
Reduced Intensity

Haploidentical Allogeneic Hematopoietic Cell Transplantation in Adults with Reduced-Intensity Conditioning and CD3/CD19-Depleted Grafts: Low Toxicity and Fast Engraftment.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3136-3136
Author(s):  
Wolfgang A. Bethge ◽  
Christoph Faul ◽  
Martin Bornhaeuser ◽  
Gernot Stuhler ◽  
Peter Lang ◽  
...  
Keyword(s):  
Stem Cells ◽  
High Risk ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
Adenoviral Infection ◽  
Grade Ii ◽  
Reduced Intensity

Abstract Haploidentical hematopoietic cell transplantation (HHCT) after high dose conditioning with CD34-selected stem cells has been complicated by high regimen related toxicities, slow engraftment and delayed immune reconstitution leading to increased treatment related mortality (TRM). A new regimen using graft CD3/CD19 depletion with anti-CD3 and anti-CD19 coated microbeads on a CliniMACS device and reduced intensity conditioning may allow HHCT with lower toxicity and faster engraftment. CD3/CD19 depleted grafts not only contain CD34+ stem cells but also CD34 negative progenitors, natural killer-, graft-facilitating- and dendritic-cells. 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) and no posttransplant immunosuppression. Twenty two consecutive patients (median age=43 (range, 21–59) years) have been transplanted with this regimen. Diagnosis were AML (n=12), ALL (n=5), NHL (n=2), MM (n=2) and CML (n=1). Patients were “high risk” with refractory disease or relapse after preceding HCT. The CD3/CD19 depleted haploidentical grafts contained a median of 7.6 x 106 (range, 3.4–17x106) CD34+cells/kg, 6.7x107 (range, 0.02–18.2 x107) CD56+cells/kg and 5.5x104(range, 0.006–44x104) CD3+T-cells/kg. Donor-recipient KIR-ligand-mismatch was found in 14 of 22 patients. The regimen was well tolerated with maximum acute toxicity being grade 2–3 mucositis. Because of severe neurotoxicity in 4 patients treated with 200 mg/m² fludarabine, the dose was reduced to 150 mg/m² with no further cases of neuropathy thereafter. Engraftment was rapid with median time to >500 granulocytes/μL of 12 (range, 10–21) days, >20000 platelets/μL of 11 (range, 7–28) days and full donor chimerism after 2–4 weeks in all patients. Incidence of grade II–IV GVHD was 59% with grade II=9, III=2 and IV=2. One patient, who received the highest T cell dose, developed lethal grade IV GVHD. TRM in the first 100 days was 6/22 (27%) with deaths due to idiopathic pneumonia syndrome (n=1), mucormycosis (n=1), pneumonia (n=3) or GVHD (n=1). Six patients died after day 100, five due to relapse and one with systemic adenoviral infection. Overall survival is 10/22 patients (45%) with a median follow-up of 185 days (range, 17–988). In conclusion, this regimen is promising in high risk patients lacking a suitable donor, and a prospective phase I/II study is ongoing.

Sign in / Sign up

Export Citation Format

Share Document