Abstract
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.
. | 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 |
. | 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.
Disclosures: Daily IV busulfan & Thymoglobulin are off label I believe.; ESP Pharma.; Genzyme.; Speakers bureau Genzyme & ESP.
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