Clinical and molecular profile of the HCL with unmutated IGHV not benefiting from cladribine
| Patient . | HCL11 . | HCL30 . | HCL49 . | HCL50 . | HCL119 . |
|---|---|---|---|---|---|
| WHO 2008 classification19 | Classic | Classic | Classic | Classic | Classic |
| Clinical parameters | |||||
| Spleen, cm bcm | 11 | 11 | 11 | 0 | 14 |
| Enlarged lymph nodes | − | + | − | − | − |
| Hemoglobin, g/dL | 15 | 11.1 | 5.2 | 10.9 | 13.4 |
| Platelets, ×109/L | 77 | 87 | 35 | 50 | 157 |
| WBCs, ×109/L | 3.5 | 10.9 | 36.4 | 1.2 | 19.4 |
| Neutrophils, ×109/L | 1.5 | 0.4 | 0.7 | 0.3 | 2.7 |
| Hairy cells, ×109/L | 0.5 | 10.5 | 28.8 | 0.3 | 10.7 |
| B2M, mg/dL | 1.0 | 1.1 | 2.2 | 1.9 | 2.9 |
| LDH, IU/L | 302 | 183 | 561 | 290 | 399 |
| Immunophenotype | |||||
| CD5 | − | − | − | − | − |
| CD11c | + | + | + | + | + |
| CD23 | − | − | − | − | − |
| CD25 | + | + | + | + | + |
| CD27 | − | − | − | − | − |
| CD38 | − | − | − | − | − |
| CD103 | + | + | + | + | + |
| FMC7 | + | + | + | + | + |
| Surface Ig isotypes | MA | MDGA | MDGA | MDGA | MG |
| Bone marrow histology | |||||
| CD20/ANXA1 | + | + | + | + | + |
| DBA44 | + | + | + | + | + |
| CD11c | + | + | + | + | + |
| bcl1 | + | + | + | + | + |
| Molecular profile | |||||
| IGHV | 3-09 | 3-23 | 3-33 | 3-33 | 4-34 |
| Homology, percentage | 98.4 | 98.3 | 98.7 | 99.1 | 99.65 |
| IGHD | 6-13 | 3-10 | 1-26 | 1-26 | 3-03 |
| IGHJ | 5 | 6 | 3 | 4 | 5 |
| IGK/LV | IGKV6-21 | IGLV2-5 | IGLV1-47 | IGLV1-47 | IGKV3-15 |
| Homology, percentage | 99,24 | 91,22 | 98,33 | 98,23 | 99,64 |
| IGK/LJ | KJ1 | LJ1 | LJ3 | LJ3 | KJ4 |
| LCDR3 subset* | − | − | 1L | 1L | − |
| TP53 | Mut | WT | Mut | WT | WT |
| Clinical course | |||||
| Response to first line | mR | NR | NR | mR | mR |
| EFS, mo | 20 | 4 | 2 | 8 | 7 |
| Second-line treatment | Rituximab | Rituximab | IFN-α | DCF | IFN-α |
| Response to second line | NR | CR | NR | PR | − |
| Other lines | IFN-α | − | − | − | − |
| Last follow-up, mo | 38 | 17 | 3 | 33 | 13 |
| Status at last follow-up | IFN-α | Stable | Dead | Stable | IFN-α |
| Patient . | HCL11 . | HCL30 . | HCL49 . | HCL50 . | HCL119 . |
|---|---|---|---|---|---|
| WHO 2008 classification19 | Classic | Classic | Classic | Classic | Classic |
| Clinical parameters | |||||
| Spleen, cm bcm | 11 | 11 | 11 | 0 | 14 |
| Enlarged lymph nodes | − | + | − | − | − |
| Hemoglobin, g/dL | 15 | 11.1 | 5.2 | 10.9 | 13.4 |
| Platelets, ×109/L | 77 | 87 | 35 | 50 | 157 |
| WBCs, ×109/L | 3.5 | 10.9 | 36.4 | 1.2 | 19.4 |
| Neutrophils, ×109/L | 1.5 | 0.4 | 0.7 | 0.3 | 2.7 |
| Hairy cells, ×109/L | 0.5 | 10.5 | 28.8 | 0.3 | 10.7 |
| B2M, mg/dL | 1.0 | 1.1 | 2.2 | 1.9 | 2.9 |
| LDH, IU/L | 302 | 183 | 561 | 290 | 399 |
| Immunophenotype | |||||
| CD5 | − | − | − | − | − |
| CD11c | + | + | + | + | + |
| CD23 | − | − | − | − | − |
| CD25 | + | + | + | + | + |
| CD27 | − | − | − | − | − |
| CD38 | − | − | − | − | − |
| CD103 | + | + | + | + | + |
| FMC7 | + | + | + | + | + |
| Surface Ig isotypes | MA | MDGA | MDGA | MDGA | MG |
| Bone marrow histology | |||||
| CD20/ANXA1 | + | + | + | + | + |
| DBA44 | + | + | + | + | + |
| CD11c | + | + | + | + | + |
| bcl1 | + | + | + | + | + |
| Molecular profile | |||||
| IGHV | 3-09 | 3-23 | 3-33 | 3-33 | 4-34 |
| Homology, percentage | 98.4 | 98.3 | 98.7 | 99.1 | 99.65 |
| IGHD | 6-13 | 3-10 | 1-26 | 1-26 | 3-03 |
| IGHJ | 5 | 6 | 3 | 4 | 5 |
| IGK/LV | IGKV6-21 | IGLV2-5 | IGLV1-47 | IGLV1-47 | IGKV3-15 |
| Homology, percentage | 99,24 | 91,22 | 98,33 | 98,23 | 99,64 |
| IGK/LJ | KJ1 | LJ1 | LJ3 | LJ3 | KJ4 |
| LCDR3 subset* | − | − | 1L | 1L | − |
| TP53 | Mut | WT | Mut | WT | WT |
| Clinical course | |||||
| Response to first line | mR | NR | NR | mR | mR |
| EFS, mo | 20 | 4 | 2 | 8 | 7 |
| Second-line treatment | Rituximab | Rituximab | IFN-α | DCF | IFN-α |
| Response to second line | NR | CR | NR | PR | − |
| Other lines | IFN-α | − | − | − | − |
| Last follow-up, mo | 38 | 17 | 3 | 33 | 13 |
| Status at last follow-up | IFN-α | Stable | Dead | Stable | IFN-α |
WBCs indicates white blood cells; B2M, β2-microglobulin; LDH, lactic dehydrogenase; −, negative; +, positive; Mut, mutation leading to p53 dysfunction; WT, wild type; EFS, event-free survival; CR, complete response; PR, partial response; mR, minor response; cm, centimeter; bcm, below costal margin; and NR, no response.
Subsets were identified according to Forconi et al.22 The remaining one UM-HCL patient (case HCL74), who obtained a PR and has not progressed after a follow-up of 27 months from end of cladribine, had no leukocytosis (hemoglobin, 9.9 g/dL; platelets, 169 × 109/L; WBCs, 1.04 × 109/L), no bulky spleen (0 cm bcm), classic peripheral blood immunophenotype, and bone marrow immunohistochemistry, and no TP53 mutations.