Preliminary results of a phase II trial of clofarabine with busulfan followed by allogeneic related or unrelated donor transplantation for the treatment of haematologic malignancies

Ref ID: 18595

Author:

E. Agura, E. Vance, R. Berryman, L. Pineiro, G. Saracino,
R. Woelfel, M. Tadic-Ovcina, J. Fay

Author address:

Baylor University Medical Center (Dallas, US)

Full conference title:

Annual Meeting of the EBMT, 36th

Abstract:

Background: We tested a novel reduced-intensity transplant
(RIT) regimen: clofarabine (CLO) with busulfan (BU) followed
by donor allografting, (CLO/BU/Allo).
Methods: Allograft candidates likely to benefi t from RIT were
selected. Disease criteria included: MDS (IPSS ≥ 2.5), acute
leukemia (AML or ALL) in high-risk CR1 or beyond, CLL
(fl udarabine failures). Donors were matched at HLA A, B, C,
DR and DQ using SBT (UD) or mid-level DNA (RD). HLA match
grade: 1Ag mm or better. Regimen: CLO 40 mg/m2
iv d-8 to
d-4, BU 3.2 mg/kg/d iv d-3 & d-2, PBSC infusion d0. AGVHD
prophylaxis was tacrolimus + MTX d1,3,6. Endpoints were disease response, chimerism, toxicity and AGVHD.
Results: Treated: 13 M and 7 F of median 60 (28-71) yrs.
Diseases: AML (n = 16), ALL (n = 1), MDS (n = 2), CLL (n = 1).
Cytogenetic risk groups: fav., n = 2, int., n = 4, unfav., n = 14.
Prior therapies: chemo, n = 17, supportive care, n = 2, or
chemo + allotransplant, n = 1. Patients with AL were in relapse,
n = 13 (median BM blasts, 24% (7-48%) or remission, n = 7.
Donor status: related, n = 6, unrelated, n = 14. Median KPS,
80 (70-90)%.
Toxicities: Gr. 4 heme toxicity was seen in 100%. The median
time to ANC > 500 x 3d was 15d. Marrow engraftment (> 90%
donor @ d30) occurred in 100% of cases. There were no cases
of hepatic, cardiac, or renal RRT. Hepatic VOD requiring treatment did not occur. GVHD: The maximal grade of AGVHD by S290
day + 100 was G0 (none) = 4, GI = 13, GII = 0, GIII = 3, GIV = 0.
No deaths due to AGVHD occurred by d100.
Response, survival: All patients achieved a complete remission following the transplant. The CR rate at d + 30 was 19/20
(95%). (CCR, n = 6, new CR, n = 12). One case of PR at d + 30
became CR at d + 90. Relapse occurred in 4 patients (day + 60,
+ 62, + 120, + 335). The mean time to relapse is 144 days. With
median length of followup of 454 (74-954) days, the overall survival (OS) is n = 11/20 (55%). Causes of death include relapse,
n = 4, ( + 161, + 220, + 223 + 415), cardiac arrest, n = 1 ( + 316),
TTP, n = 1 ( + 438), AGVHD P DLI, n = 1 ( + 175), aspergillosis,
n = 1 ( + 158), multifactorial, n = 1 ( + 92).
Pharmacokinetics: The average concentration of clofarabine declined signifi cantly from day 1 (265 ± 66 ng/ml) to day 5
(238 ± 61 ng/ml) (P = 0.03). Other clinical correlations with are
under study.
Conclusions: The novel RIT regimen CLO/BU/Allo has high
activity against myeloid and lymphoid malignancies, facilitates
engraftment, and has a low non-hematologic toxicities including
AGVHD. These results warrant further study.

Abstract Number: P931

Conference Year: 2010

Link to conference website: NULL

New link: NULL

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