Hematopoietic Stem Cell Transplantation (SCT) for Hematologic Malignancy from 10/10 Matched Unrelated Donors (MUD) with a Myeloablative Once Daily IV Fludarabine (Flu)/Busulfan Based Regimen (FLUBUP) with Thymoglobulin: Outcomes According to Stem Cell Source.
Authors: Russell James A. , Chaudhry M. Ahsan , Geddes Michelle , Bahlis Nizar J. , Savoie Mary Lynn , Larratt Loree M. , Quinlan Diana M. , Turner A. Robert , Balogh Alexander , Storek Jan , Brown Christopher , Stewart Douglas A. 
Published: October 2019

Since 1999 we have used FLUBUP for all patients (pts) with hematologic malignancy including those who might be considered candidates for nonmyelablative SCT. Eighty-four pts were transplanted with marrow (BMT) or blood (BCT) from unrelated donors matched for HLA-A, -B, C, DR and DQ between 05/99 and 07/05. Chemotherapy comprised Flu 50mg/m2 on days -6 to -2 and IV Bu (Busulfex, PDL Pharma) 3.2 mg/kg daily days -5 to -2 inclusive. Thirty-four pts had additional TBI 200cGy x 2 on day -1 or 0. Prophylaxis for GVHD was cyclosporine A, methotrexate with folinic acid and Thymoglobulin (Genzyme) 4.5 mg/kg in divided doses over 3 consecutive days pretransplant finishing day (D) 0. Follow-up of survivors was 12–82 months (median 33). Two BMT pts were unevaluable for engraftment (died before D28), one relapsed before AGC engraftment and 2 had graft failure (GF). Two additional pts died of relapse and one of transplant-related causes without platelet engraftment. Granulocytes engrafted in all BCT recipients, 2 died before D28 and 2 later of relapse without platelet engraftment.

Details of Recipients, SCT and Outcomes BMT BCT Number 49 35 Patient age median (range) 40 (16–60) 41 (19–61) ns Donor age median (range) 32 (19–51) 29 (20–57) ns Low risk (Acute leukemia (AL) CR1/2, CML CP1) 23 (47%) (AML 8 CR1, 4 CR2, ALL 5 CR1, 1 CR2, 5 CML CP1) 22 (62%) (AML 10 CR1, 8 CR2, ALL 2 CR1, 3 CR 2, AUL 1 CR1) ns High risk 26 (53%) ( 11 active AL, 2 CML AP, 3 CLL, 1 CMML, 4 MDS, 1 MF, 3 NHL) 13 (38%) (5 active AL, 1 CML AP, 1 MM/MDS, 2 MDS,1 MF, 1 HD/CLL, 1 HD, 1 CLL) ns CMV+ve Recipient or Donor D 35 (71%) 23 (66%) ns Female to male SCT 13 (27%) 3 (9%) 0.05 Male pt 29 (59%) 18 (51%) ns TBI (not TRM risk factor) 11 (22%) 23 (66%) 0.0001 CD34+ cell dose x 10e6/kg median (range) 2.7 (0.44–18.32) 7.47 (1.36–23.87) <0.0001 Median AGC recovery (D) (range) 19 (13–113) 15 (10–46) <0.0001 Median platelet recovery (D) (range) 28 (15–120) 18 (5–67) <0.0001 Acute GVHD II–IV 19±2% 21±7% ns Acute GVHD III–IV 9±4% 12±6% ns Chronic GVHD 77±8% 53±10% ns Low risk TRM (3 years) 22±9% 0 0.03 High risk TRM 43±12% 39±14% ns Primary cause of non-relapse death <D100 PTLD (1), sudden death cause unknown (1), HUS (1), aspiration pneumonia (1) Pneumonia (1), multiorgan failure (2), PTLD (1) Primary cause of non-relapse death >D100 GVHD related (5), primary GF (2), infection (2) Secondary GF (1) Low risk survival 70±10% 81±9% ns High risk survival 33±10% 54±14% ns

In low-risk pts FLUBUP appears to be relatively well-tolerated and TRM is lower after BCT. Infection and PTLD contribute as much as GVHD to TRM so there may be little to gain by changing ATG dose or timing. Engraftment is faster after BCT as expected but there is no difference in acute or chronic GVHD. In general therefore, BCT seems preferable to BMT for MUD SCT with this protocol.