Patient and transplant characteristics, ungrouped and by alemtuzumab exposure
Characteristic . | Ungrouped . | By median exposure . | ||
---|---|---|---|---|
N = 53∗ . | Low exposure, n = 27∗ . | High exposure, n = 26∗ . | P value† . | |
Diagnosis | .012 | |||
ADA2 deficiency | 1 (1.9%) | 0 (0%) | 1 (3.8%) | |
APDS type 1 | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
CGD | 8 (15%) | 5 (19%) | 3 (12%) | |
CID | 1 (1.9%) | 0 (0%) | 1 (3.8%) | |
Congenital severe thrombopenia | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
CTLA-4 deficiency | 1 (1.9%) | 0 (0%) | 1 (3.8%) | |
DOCK8 mutation | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
HLH | 7 (13%) | 4 (15%) | 3 (12%) | |
Hyper-IgE syndrome | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
IFNgR1 deficiency | 7 (13%) | 5 (19%) | 2 (7.7%) | |
IL10RB deficiency | 2 (3.8%) | 2 (7.4%) | 0 (0%) | |
IPEX | 2 (3.8%) | 2 (7.4%) | 0 (0%) | |
MKL1 mutation | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
SAA | 6 (11%) | 0 (0%) | 6 (23%) | |
SCID | 10 (19%) | 2 (7.4%) | 8 (31%) | |
Shwachman-Diamond syndrome | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
STIM1 | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
WAS | 1 (1.9%) | 0 (0%) | 1 (3.8%) | |
Diagnosis category | .14 | |||
Hematological | 8 (15%) | 2 (7.4%) | 6 (23%) | |
IEI | 45 (85%) | 25 (93%) | 20 (77%) | |
Sex | .5 | |||
Female | 20 (38%) | 9 (33%) | 11 (42%) | |
Male | 33 (62%) | 18 (67%) | 15 (58%) | |
Age at HSCT, y | 4.4 (0.8-8.7) | 4.0 (0.7-8.6) | 4.9 (1.4-9.8) | .5 |
Alemtuzumab treatment | ||||
Cumulative dose mg/kg, | 0.60 (0.60-1.00) | 0.60 (0.55-0.60) | 0.90 (0.60-1.00) | .01 |
Start day before HSCT | −11.0 (−14.0 to −8.0) | −12.0 (−14.0 to −10.0) | −8.0 (−11.8 to −7.2) | .003 |
No. of doses | 4 (2-7) | 3 (3-4) | 4 (3-5) | .069 |
Conditioning | .021 | |||
Busulfan, fludarabine | 12 (23%) | 5 (19%) | 7 (27%) | |
Fludarabine, cyclophosphamide | 6 (11%) | 0 (0%) | 6 (23%) | |
Fludarabine, treosulfan | 18 (34%) | 10 (37%) | 8 (31%) | |
Fludarabine, treosulfan, thiotepa | 17 (32%) | 12 (44%) | 5 (19%) | |
Intensity of conditioning | .2 | |||
Myeloablative | 21 (40%) | 13 (48%) | 8 (31%) | |
Reduced | 32 (60%) | 14 (52%) | 18 (69%) | |
GVHD prophylaxis | .3 | |||
Cyclosporine | 7 (13%) | 2 (7%) | 5 (19%) | |
Cyclosporine, MMF | 15 (28%) | 7 (26%) | 8 (31%) | |
Cyclosporine, MTX | 23 (43%) | 12 (44%) | 11 (42%) | |
MTX, MMF | 1 (2%) | 1 (4%) | 0 (0%) | |
Cyclosporine, MMF, post-cyclophosphamide | 5 (9%) | 5 (19%) | 0 (0%) | |
No | 2 (4%) | 0 (0%) | 2 (8%) | |
Graft source | .7 | |||
BM | 39 (74%) | 21 (78%) | 18 (69%) | |
CB | 6 (11%) | 2 (7.4%) | 4 (15%) | |
PBSC | 8 (15%) | 4 (15%) | 4 (15%) | |
Graft manipulation | .7 | |||
CD34 selection | 5 (10%) | 2 (7%) | 3 (12%) | |
No | 48 (91%) | 25 (93%) | 23 (88%) | |
Donor type | .025 | |||
MRD | 12 (23%) | 10 (37%) | 2 (8%) | |
HAPLO | 2 (3.8%) | 0 (0%) | 2 (8%) | |
MMD | 17 (32%) | 6 (22%) | 11 (42%) | |
MUD | 22 (42%) | 11 (41%) | 11 (42%) | |
Follow-up post-HSCT, y | 3.3 (2.5-8.0) | 2.8 (2.0-3.7) | 6.8 (2.8-10.6) | .005 |
Characteristic . | Ungrouped . | By median exposure . | ||
---|---|---|---|---|
N = 53∗ . | Low exposure, n = 27∗ . | High exposure, n = 26∗ . | P value† . | |
Diagnosis | .012 | |||
ADA2 deficiency | 1 (1.9%) | 0 (0%) | 1 (3.8%) | |
APDS type 1 | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
CGD | 8 (15%) | 5 (19%) | 3 (12%) | |
CID | 1 (1.9%) | 0 (0%) | 1 (3.8%) | |
Congenital severe thrombopenia | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
CTLA-4 deficiency | 1 (1.9%) | 0 (0%) | 1 (3.8%) | |
DOCK8 mutation | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
HLH | 7 (13%) | 4 (15%) | 3 (12%) | |
Hyper-IgE syndrome | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
IFNgR1 deficiency | 7 (13%) | 5 (19%) | 2 (7.7%) | |
IL10RB deficiency | 2 (3.8%) | 2 (7.4%) | 0 (0%) | |
IPEX | 2 (3.8%) | 2 (7.4%) | 0 (0%) | |
MKL1 mutation | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
SAA | 6 (11%) | 0 (0%) | 6 (23%) | |
SCID | 10 (19%) | 2 (7.4%) | 8 (31%) | |
Shwachman-Diamond syndrome | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
STIM1 | 1 (1.9%) | 1 (3.7%) | 0 (0%) | |
WAS | 1 (1.9%) | 0 (0%) | 1 (3.8%) | |
Diagnosis category | .14 | |||
Hematological | 8 (15%) | 2 (7.4%) | 6 (23%) | |
IEI | 45 (85%) | 25 (93%) | 20 (77%) | |
Sex | .5 | |||
Female | 20 (38%) | 9 (33%) | 11 (42%) | |
Male | 33 (62%) | 18 (67%) | 15 (58%) | |
Age at HSCT, y | 4.4 (0.8-8.7) | 4.0 (0.7-8.6) | 4.9 (1.4-9.8) | .5 |
Alemtuzumab treatment | ||||
Cumulative dose mg/kg, | 0.60 (0.60-1.00) | 0.60 (0.55-0.60) | 0.90 (0.60-1.00) | .01 |
Start day before HSCT | −11.0 (−14.0 to −8.0) | −12.0 (−14.0 to −10.0) | −8.0 (−11.8 to −7.2) | .003 |
No. of doses | 4 (2-7) | 3 (3-4) | 4 (3-5) | .069 |
Conditioning | .021 | |||
Busulfan, fludarabine | 12 (23%) | 5 (19%) | 7 (27%) | |
Fludarabine, cyclophosphamide | 6 (11%) | 0 (0%) | 6 (23%) | |
Fludarabine, treosulfan | 18 (34%) | 10 (37%) | 8 (31%) | |
Fludarabine, treosulfan, thiotepa | 17 (32%) | 12 (44%) | 5 (19%) | |
Intensity of conditioning | .2 | |||
Myeloablative | 21 (40%) | 13 (48%) | 8 (31%) | |
Reduced | 32 (60%) | 14 (52%) | 18 (69%) | |
GVHD prophylaxis | .3 | |||
Cyclosporine | 7 (13%) | 2 (7%) | 5 (19%) | |
Cyclosporine, MMF | 15 (28%) | 7 (26%) | 8 (31%) | |
Cyclosporine, MTX | 23 (43%) | 12 (44%) | 11 (42%) | |
MTX, MMF | 1 (2%) | 1 (4%) | 0 (0%) | |
Cyclosporine, MMF, post-cyclophosphamide | 5 (9%) | 5 (19%) | 0 (0%) | |
No | 2 (4%) | 0 (0%) | 2 (8%) | |
Graft source | .7 | |||
BM | 39 (74%) | 21 (78%) | 18 (69%) | |
CB | 6 (11%) | 2 (7.4%) | 4 (15%) | |
PBSC | 8 (15%) | 4 (15%) | 4 (15%) | |
Graft manipulation | .7 | |||
CD34 selection | 5 (10%) | 2 (7%) | 3 (12%) | |
No | 48 (91%) | 25 (93%) | 23 (88%) | |
Donor type | .025 | |||
MRD | 12 (23%) | 10 (37%) | 2 (8%) | |
HAPLO | 2 (3.8%) | 0 (0%) | 2 (8%) | |
MMD | 17 (32%) | 6 (22%) | 11 (42%) | |
MUD | 22 (42%) | 11 (41%) | 11 (42%) | |
Follow-up post-HSCT, y | 3.3 (2.5-8.0) | 2.8 (2.0-3.7) | 6.8 (2.8-10.6) | .005 |
Based on the median alemtuzumab concentration at day of HSCT (0.77 μg/mL), patients were stratified into the high-exposure (>0.77 μg/mL) or low-exposure groups (≤0.77 μg/mL).
ADA2, adenosine deaminase; APDS, activated PI3 kinase delta syndrome; BM, bone marrow; CB, cord blood; CGD, chronic granulomatous disease; CTLA4, cytotoxic T-lymphocyte associated protein 4; CID, combined immunodeficiency; DOCK8, dedicator of cytokinesis 8; HAPLO, haploidentical; HLH, hemophagocytic lymphohistiocytosis; IgG, immunoglobulin G; IEI, inborn errors of immunity; IFNgR1, interferon γ receptor 1; IL10RB, interleukin 10 receptor subunit β; IPEX, immunodysregulation polyendocrinopathy enteropathy X-linked syndrome; MMD, mismatched donors; MMF, mycophenolate mofetil; MRD, matched related donors; MTX, methotrexate; MUD, matched unrelated donors; PBSC, peripheral blood stem cells; SAA, severe aplastic anemia; SCID, severe combined immunodeficiency; STIM1, stromal interaction molecule; WAS, Wiskott-Aldrich syndrome.
n (%); median (interquartile range).
Fisher exact test; Pearson χ2 test; Wilcoxon rank-sum test.