Characteristics of patients, HSCT, and posttransplant AIHA
| . | Patient 1 . | Patient 2 . | Patient 3 . |
|---|---|---|---|
| Diagnosis | Pre–B-ALL | XLT/WAS | DNA-ligase IV deficiency |
| Age at HSCT | 19 y | 25 mo | 20 mo |
| Donor | MUD (11/12, HLA-DP locus) | MUD (9/10, B locus) | MFD |
| Conditioning regimen | Bu (targeted cAUC 90); Flu (40 mg/m2); Clo (120 mg/m2); alemtuzumab (0.6 mg/kg) | Treo (36 g/m2); Flu (150 mg/m2); Thio (10 mg/kg); alemtuzumab (0.7 mg/kg) | Flu (150 mg/m2); Cy (20 mg/kg); alemtuzumab (1 mg/kg) |
| Blood groups, recipient/donor | A+/A+ | 0+/0+ | 0+/0+ |
| Onset of post-HSCT AIHA, days post-HSCT | 116 | 138 | 286 |
| Chimerism at diagnosis, % donor cells | 92 | 100 | 95 |
| Isotype/specific antibodies | IgG/anti Rh-E-antigen | IgG/warm autoantibody | IgG/anti-RH5 antibody |
| Activation of complement | Yes | No | Yes |
| Immunological phenotyping at onset of AIHA | ND | CD4+ 48/μL, CD19+ 108/μL, CD56+/CD16+ 192/μL | CD4+ 792/μL, CD19+ 528/μL, CD56+/CD16+ 44/μL |
| PRBC transfusions prior to daratumumab | ∼200 (total) | 20 | 4 |
| Cumulative days of steroid treatment* prior to daratumumab | 503 | 54 | 379 |
| Initial treatment | MPN, rituximab | PDN, rituximab, plasmapheresis | MPN/PDN, rituximab |
| Plasmapheresis sessions | No | 36 | No |
| Cumulative number of rituximab doses, ×375 mg/m2, prior to daratumumab | 11 | 8 | 7 |
| Cumulative number of bortezomib courses, 4 × 1.3 mg/m2, prior to daratumumab | 3 | 2 | 3 |
| Ongoing second- or third-line treatments at start of daratumumab treatment | Bortezomib, sirolimus, MMF, ibrutinib, Cy, ATG | MMF, plasmapheresis | MMF, sirolimus, eculizumab |
| Day of start daratumumab after onset of AIHA (post-HSCT day+) | 503 (619) | 265 (403) | 333 (619) |
| Total doses of daratumumab, ×16 mg/kg, given once weekly | 11 | 4 | 7 |
| Duration of daratumumab treatment, d | 49 | 17 | 43 |
| Response to daratumumab | Partial/transient (8 mo) | Yes | Yes |
| PRBC following daratumumab | Until death | None | 1 |
| Outcome (follow-up time in months after daratumumab/rituximab) | Died | a/w (16/12) | a/w (13/19) |
| CD4+ T cells, CD45RA % | NA | 1898/μL, 75% | 1565/μL, 44% |
| Time to B-cell recovery, mo | NA | 7.5 | 6.5 |
| CD19+CD20+ B-cell recovery at last follow-up | NA | 164/μL | 656/μL |
| IgM | NA | 0.44 g/L | 0.42 g/L |
| CD19+CD38++ plasmablasts | NA | Present | Present |
| On IVIG | Until death | No | Yes |
| . | Patient 1 . | Patient 2 . | Patient 3 . |
|---|---|---|---|
| Diagnosis | Pre–B-ALL | XLT/WAS | DNA-ligase IV deficiency |
| Age at HSCT | 19 y | 25 mo | 20 mo |
| Donor | MUD (11/12, HLA-DP locus) | MUD (9/10, B locus) | MFD |
| Conditioning regimen | Bu (targeted cAUC 90); Flu (40 mg/m2); Clo (120 mg/m2); alemtuzumab (0.6 mg/kg) | Treo (36 g/m2); Flu (150 mg/m2); Thio (10 mg/kg); alemtuzumab (0.7 mg/kg) | Flu (150 mg/m2); Cy (20 mg/kg); alemtuzumab (1 mg/kg) |
| Blood groups, recipient/donor | A+/A+ | 0+/0+ | 0+/0+ |
| Onset of post-HSCT AIHA, days post-HSCT | 116 | 138 | 286 |
| Chimerism at diagnosis, % donor cells | 92 | 100 | 95 |
| Isotype/specific antibodies | IgG/anti Rh-E-antigen | IgG/warm autoantibody | IgG/anti-RH5 antibody |
| Activation of complement | Yes | No | Yes |
| Immunological phenotyping at onset of AIHA | ND | CD4+ 48/μL, CD19+ 108/μL, CD56+/CD16+ 192/μL | CD4+ 792/μL, CD19+ 528/μL, CD56+/CD16+ 44/μL |
| PRBC transfusions prior to daratumumab | ∼200 (total) | 20 | 4 |
| Cumulative days of steroid treatment* prior to daratumumab | 503 | 54 | 379 |
| Initial treatment | MPN, rituximab | PDN, rituximab, plasmapheresis | MPN/PDN, rituximab |
| Plasmapheresis sessions | No | 36 | No |
| Cumulative number of rituximab doses, ×375 mg/m2, prior to daratumumab | 11 | 8 | 7 |
| Cumulative number of bortezomib courses, 4 × 1.3 mg/m2, prior to daratumumab | 3 | 2 | 3 |
| Ongoing second- or third-line treatments at start of daratumumab treatment | Bortezomib, sirolimus, MMF, ibrutinib, Cy, ATG | MMF, plasmapheresis | MMF, sirolimus, eculizumab |
| Day of start daratumumab after onset of AIHA (post-HSCT day+) | 503 (619) | 265 (403) | 333 (619) |
| Total doses of daratumumab, ×16 mg/kg, given once weekly | 11 | 4 | 7 |
| Duration of daratumumab treatment, d | 49 | 17 | 43 |
| Response to daratumumab | Partial/transient (8 mo) | Yes | Yes |
| PRBC following daratumumab | Until death | None | 1 |
| Outcome (follow-up time in months after daratumumab/rituximab) | Died | a/w (16/12) | a/w (13/19) |
| CD4+ T cells, CD45RA % | NA | 1898/μL, 75% | 1565/μL, 44% |
| Time to B-cell recovery, mo | NA | 7.5 | 6.5 |
| CD19+CD20+ B-cell recovery at last follow-up | NA | 164/μL | 656/μL |
| IgM | NA | 0.44 g/L | 0.42 g/L |
| CD19+CD38++ plasmablasts | NA | Present | Present |
| On IVIG | Until death | No | Yes |
a/w, alive and well; B ALL, B-cell acute lymphocytic leukemia; Bu, busulfan; Clo, clofarabine; cAUC, cumulative area under the curve; Cy, cyclophosphamide; HLA-DP, human leucocyte antigen DP; Flu, fludarabine; MFD, matched family donor; NA, not applicable; ND, not done; PDN, prednisolone; Thio, thiotepa; Treo, treosulfan; WAS, Wiskott-Aldrich syndrome; XLT, X-linked thrombocytopenia.
PDN ≥ 1 mg/kg.