Low-dose busulfan/full-dose 64258; udarabine-based reduced-intensity conditioning in 30 high-risk paediatric and adult chronic granulomatous disease patients

Ref ID: 18602

Author:

T. Güngör, M. Albert, U. Schanz, M. Slatter, A. Gennery,
A. Waver, P. Teira, E. Haddad, I. Ahmad, S. Lachance, P.J. Shaw,
P. Stepensky, I. Resnik, R. Seger, M. Hassan on behalf of the
Working Party Inborn Errors

Author address:

NULL

Full conference title:

Annual Meeting of the EBMT, 37th

Abstract:

Objective: To examine the effi cacy and safety of hematopoietic stem cell transplantation (HSCT) after low-dose (50-65 %)
Busulfan, full-dose Fludarabine conditioning and in-vivo T-cell
depletion in high-risk pediatric and adult chronic granulomatous
disease (CGD) patients.
Patients and methods: 30 CGD patients (4-39; median 11 ys)
with X-linked (n=19) and autosomal recessive (n=11) disease are
described. The majority of patients were refractory to treatment
suffering from infectious and/or infl ammatory complications, e.g.
granulomatous colitis (n=13), active infection (e.g. Aspergillus)
(n=15) or oxygene-dependent restrictive lung disease (n=2).
Stem cell donors were 14 matched sibling/related donors and
11 MUD (10/10) and 5 MMUD (9/10) donors. Conditioning
comprised 180 mg/sqm Fludarabine (d -8 to -3) and oral/iv.
Busulfan (6.4-12 mg/kg; d -4 to -2). Pediatric patients received
a therapeutic drug monitoring aiming at a cumulative AUC of
Busulfan between 45 to 65 mg/L x h. For in-vivo T-cell depletion
ATG-Fresenius (40 mg/kg) or Thymoglobuline-Genzyme (7.5
mg/kg) were administered.
Pediatric CGD (4-17 ys) patients with MUD/MMUD transplants
received Alemtuzumab (0.5 mg/kg; d -8 to -6) instead of ATG. Bone
marrow (2.3-6.0 x 10 6 CD34/kg) was the prefered stem cell source,
three patients received PBSC (5-11 x 10 6 CD34/kg). GVHD-prophylaxis comprised mainly CSA and MMF and in a few cases MTX.
Results: The follow-up period is 2-97 (median 10) months.
Acute GVHD I-II was encountered in 11 patients. No serious
infectious or infl ammatory fl are-ups were observed. Neutrophil
(d +19-26) and platelet engraftment (d +21-25) was in time.
Three limited chronic GVHD (limited to skin) were observed.
The disease-free survival is 93 % (28/30). The overall survival
is 97 % (29/30). Two patients with a low cumulative AUC for
Busulfan under 45 mg/L x h had autologuous reconstitution.
Both were retransplanted. Two patients had transient pure
red cell aplasias. Twenty-eight patients are alive and well with
stable (95-100%) donor myeloid chimerism. NBT-/DHR-tests
are normalized. All active infl ammatory and infectious foci are
cured. One adult patient fathered a child after HSCT. Despite
full myeloid engraftment, one adult patient died due to pulmonary failure (d+187). Conclusion: This RIC regimen is effi cacious and well-tolerated in both pediatric and adult high-risk
CGD-patients. Targeting Busulfan is regarded to be of major
importance to prevent autologous reconstitution.

Abstract Number: O170

Conference Year: 2011

Link to conference website: NULL

New link: NULL

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