Patient characteristics and outcome for the entire HLH-2004 cohort, for subgroups of the HLH-2004 cohort, and, for comparison, data from the study HLH-94
| . | HLH-2004 . | . | ||||
|---|---|---|---|---|---|---|
| n = 369 . | Verified FHL,* n = 168 . | Not verified FHL,* n = 201 . | HLH-94 criteria,† n = 240 . | HLH-2004 criteria only,‡ n = 129 . | HLH-94 n = 232 . | |
| General information | ||||||
| Median age at onset, mo | 12.6 | 3.4 | 21.4 | 13.0 | 12.6 | 8.3 |
| Male sex (%) | 187 (51) | 77 (46) | 110 (55) | 118 (49) | 69 (53) | 123 (53) |
| Consanguinity (%) | 58 (16) | 50 (30) | 8 (4) | 39 (17) | 19 (16) | 43 (19) |
| Verified FHL* | 168 (46) | 168 (100) | N.A. | 121 (50) | 47 (36) | 52 (22) |
| Affected sibling (% of all) | 47 (13) | 47 (28) | N.A. | 47 (20) | N.A.§ | 52 (22) |
| Biallelic FHL mutations (% of all) | 158 (43) | 158 (94) | N.A. | 111 (46) | 47 (36) | N.A. |
| Outcome | ||||||
| Dead, no HSCT (% of all) | 75 (20) | 28 (17) | 47 (23) | 46 (19) | 29 (22) | 63 (27) |
| Dead at 2 mo (% of all) | 50 (14) | 19 (11) | 31 (15) | 27 (11) | 23 (18) | 33 (14) |
| Dead at 6 mo (% of all) | 63 (17) | 22 (13) | 41 (20) | 37 (15) | 26 (20) | 46 (20) |
| Dead at 1 y (% of all) | 67 (18) | 23 (14) | 44 (22) | 41 (17) | 27 (21) | 56 (24) |
| HSCT performed (%) | 185 (50)|| | 133 (79)|| | 52 (26)|| | 133 (55)|| | 52 (40)|| | 118 (51) |
| Median time to HSCT, d | 148 | 129 | 192 | 154 | 147 | 180 |
| Alive post-HSCT (% of HSCT) | 121 (65) | 93 (70) | 29 (56) | 90 (68) | 31(60) | 78 (66)¶ |
| Dead post-HSCT (% of HSCT) | 64 (35) | 40 (30) | 23 (44) | 43 (32) | 21(40) | 40 (34) |
| Off therapy >1 y, alive without HSCT (%) | 88 (24)# | 2** (1) | 86 (43) | 48 (20) | 37 (29) | 48 (21) |
| Survival | ||||||
| 5-y pSu (95% CI) | 61 (56-67) | 59 (52-67) | 64 (57-71) | 62 (56-68) | 61 (53-70) | 56 (50-63) |
| 5-y pSu post-HSCT (95% CI) | 66 (59-73) | 70 (63-78) | 54 (40-68) | 67 (60-76) | 61 (48-74) | 66 (58-75) |
| . | HLH-2004 . | . | ||||
|---|---|---|---|---|---|---|
| n = 369 . | Verified FHL,* n = 168 . | Not verified FHL,* n = 201 . | HLH-94 criteria,† n = 240 . | HLH-2004 criteria only,‡ n = 129 . | HLH-94 n = 232 . | |
| General information | ||||||
| Median age at onset, mo | 12.6 | 3.4 | 21.4 | 13.0 | 12.6 | 8.3 |
| Male sex (%) | 187 (51) | 77 (46) | 110 (55) | 118 (49) | 69 (53) | 123 (53) |
| Consanguinity (%) | 58 (16) | 50 (30) | 8 (4) | 39 (17) | 19 (16) | 43 (19) |
| Verified FHL* | 168 (46) | 168 (100) | N.A. | 121 (50) | 47 (36) | 52 (22) |
| Affected sibling (% of all) | 47 (13) | 47 (28) | N.A. | 47 (20) | N.A.§ | 52 (22) |
| Biallelic FHL mutations (% of all) | 158 (43) | 158 (94) | N.A. | 111 (46) | 47 (36) | N.A. |
| Outcome | ||||||
| Dead, no HSCT (% of all) | 75 (20) | 28 (17) | 47 (23) | 46 (19) | 29 (22) | 63 (27) |
| Dead at 2 mo (% of all) | 50 (14) | 19 (11) | 31 (15) | 27 (11) | 23 (18) | 33 (14) |
| Dead at 6 mo (% of all) | 63 (17) | 22 (13) | 41 (20) | 37 (15) | 26 (20) | 46 (20) |
| Dead at 1 y (% of all) | 67 (18) | 23 (14) | 44 (22) | 41 (17) | 27 (21) | 56 (24) |
| HSCT performed (%) | 185 (50)|| | 133 (79)|| | 52 (26)|| | 133 (55)|| | 52 (40)|| | 118 (51) |
| Median time to HSCT, d | 148 | 129 | 192 | 154 | 147 | 180 |
| Alive post-HSCT (% of HSCT) | 121 (65) | 93 (70) | 29 (56) | 90 (68) | 31(60) | 78 (66)¶ |
| Dead post-HSCT (% of HSCT) | 64 (35) | 40 (30) | 23 (44) | 43 (32) | 21(40) | 40 (34) |
| Off therapy >1 y, alive without HSCT (%) | 88 (24)# | 2** (1) | 86 (43) | 48 (20) | 37 (29) | 48 (21) |
| Survival | ||||||
| 5-y pSu (95% CI) | 61 (56-67) | 59 (52-67) | 64 (57-71) | 62 (56-68) | 61 (53-70) | 56 (50-63) |
| 5-y pSu post-HSCT (95% CI) | 66 (59-73) | 70 (63-78) | 54 (40-68) | 67 (60-76) | 61 (48-74) | 66 (58-75) |
N.A., not applicable.
FHL was defined as having either biallelic mutations in FHL-causative genes (PRF1, UNC13D, STX11, and STXBP2) or an affected sibling, whereas in HLH-94 familial (primary) HLH was defined as having an affected sibling.
Patients within the HLH-2004 study who fulfilled the HLH-94 criteria (5 of 5).
Patients within the HLH-2004 who only fulfilled the HLH-2004 criteria (5 of 8) but not the HLH-94 criteria (5 of 5).
By definition, if a patient had an affected sibling, the patient fulfilled the HLH-94 criteria.
Altogether, 3 additional patients were reported as having received a HSCT but further information on the HSCT was missing; 2 with and 1 without verified FHL; regarding fulfilled criteria, 1 patient fulfilled the HLH-2004 criteria and 2 fulfilled the HLH-94 criteria.
Includes 1 patient who also developed acute myelogenous leukemia, received a transplantation and survived.
In addition, 18 patients were reported as alive without HSCT with <1 y follow-up, 5 of these were reported as lost to follow-up.
These 2 patients, both alive for ≥5 y after onset of therapy, displayed biallelic PRF1 p.Ala91Val mutations, sometimes considered polymorphisms.34