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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Biol+Blood+Marrow+Transplant
2015 ; 21
(8
): 1460-70
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Experience with Alemtuzumab, Fludarabine, and Melphalan Reduced-Intensity
Conditioning Hematopoietic Cell Transplantation in Patients with Nonmalignant
Diseases Reveals Good Outcomes and That the Risk of Mixed Chimerism Depends on
Underlying Disease, Stem Cell Source, and Alemtuzumab Regimen
#MMPMID25865646
Marsh RA
; Rao MB
; Gefen A
; Bellman D
; Mehta PA
; Khandelwal P
; Chandra S
; Jodele S
; Myers KC
; Grimley M
; Dandoy C
; El-Bietar J
; Kumar AR
; Leemhuis T
; Zhang K
; Bleesing JJ
; Jordan MB
; Filipovich AH
; Davies SM
Biol Blood Marrow Transplant
2015[Aug]; 21
(8
): 1460-70
PMID25865646
show ga
Alemtuzumab, fludarabine, and melphalan reduced-intensity conditioning (RIC)
regimens are increasingly used for the hematopoietic cell transplantation (HCT)
of pediatric and young adult patients with nonmalignant diseases. Early
experience suggests that these regimens are associated with good survival but a
high incidence of mixed chimerism, which we have previously shown to be
influenced by the alemtuzumab schedule. We hypothesized that the underlying
diagnosis and donor graft source would also affect the development of mixed
chimerism and that the majority of patients would survive RIC HCT without graft
loss. To examine this, we conducted a retrospective study of 206 patients with
metabolic diseases, non-Fanconi anemia marrow failure disorders, and primary
immune deficiencies who underwent 210 consecutive RIC HCT procedures at
Cincinnati Children's Hospital. Ninety-seven percent of the patients engrafted.
Mixed donor and recipient chimerism developed in 46% of patients. Patients with
marrow failure had a low risk of mixed chimerism (hazard ratio [HR], .208; 95%
confidence interval [CI], .061 to .709; P = .012). The risk of mixed chimerism
was high in patients who received a cord blood graft (HR, 3.122; 95% CI, 1.236 to
7.888; P = .016). As expected, patients who received a proximal or higher dose
per kilogram of alemtuzumab schedule also experienced higher rates of mixed
chimerism (all HR > 2, all P < .05). At the time of last follow-up (median, 654
days; range, 13 to 3337), over 75% of patients had greater than 90% whole blood
donor chimerism. A second transplantation was performed in 5% of patients.
Three-year survival without retransplantation was 84% (95% CI, 71% to 98%) for
patients who underwent transplantation with an HLA-matched sibling donor.
Survival without retransplantation was negatively affected by lack of a matched
related donor, increasing age, and development of grades III and IV acute
graft-versus-host disease. We conclude that alemtuzumab, fludarabine, and
melphalan RIC HCT offers good results for many patients and that the risk of
developing mixed chimerism is influenced by underlying diagnosis, graft source,
and alemtuzumab dosing.
|Adolescent
[MESH]
|Adult
[MESH]
|Alemtuzumab
[MESH]
|Antibodies, Monoclonal, Humanized/administration & dosage/*therapeutic use
[MESH]
|Antineoplastic Combined Chemotherapy Protocols/administration &
dosage/*therapeutic use
[MESH]