Table 1.
Recommended conditioning regimen and management of patients with idiopathic AA undergoing HSCT (adapted from UK guidelines8)
| Conditioning regimens and GVHD prophylaxis (BM as source of stem cell) | |
|---|---|
| Idiopathic AA | |
| MRD | CY 50 mg/kg × 4 (D-5 to D-2) and ATG* (5-10 mg/kg) |
| Postgraft immune suppression associates CsA (3 mg/kg D-1) and short course MTX (10 mg/m2 D+1, 8 mg/m2 D+3 and D+6) | |
| For patients aged >40†, alternative regimens are: | |
| FLU 30 mg/m2 × 4 (D-6 to D-3), CY 300 mg/m2 × 4 (D-6 to D-3) and ATG (5-10 mg/kg) (FCA regimen) or | |
| FLU 30 mg/m2 × 4 (D-6 to D-3), CY 300 mg/m2 × 4 (D-6 to D-3) and alemtuzumab 0.2 mg/kg × 5 (D-7 to D-3) (FCC regimen) | |
| Postgraft immune suppression associates CsA (3 mg/kg D-1) and short-course MTX (10 mg/m2 D+1, 8 mg/m2 D+3 and D+6), or CsA alone if using alemtuzumab | |
| MUD (refractory patients)‡ | FLU 30 mg/m2 × 4 (D-6 to D-3), CY 30 mg/kg × 4 (D-6 to D-3), ATG 3.75 mg/kg × 2 (D-4 to D-3) and TBI 2 Gy (D-1) (FCA TBI regimen) or |
| FLU 30 mg/m2 × 4 (D-6 to D-3), CY 300 mg/m2 × 4 (D-6 to D-3) and alemtuzumab 0.2 mg/kg × 5 (D-7 to D-3) (FCC regimen) | |
| Postgraft immunosuppression as for MRD | |
| For patients aged <14: | |
| FLU 30 mg/m2 × 4 (D-6 to D-3), CY 30 mg/kg × 4 (D-6 to D-3) and ATG 3.75 mg/kg × 2 (D-6 to D-3) FLU 30 mg/m2 × 4 (D-6 to D-3), CY 300 mg/m2 × 4 (D-6 to D-3) and alemtuzumab 0.2 mg/kg × 5 (D-7 to D-3) (FCC regimen) | |
| Postgraft immunosuppression as for MRD | |
| MUD (up-front transplantation)‡ | FLU 30 mg/m2 × 5 (D-7 to D-3), CY 60 mg/kg × 2 (D-3 to D-2) and alemtuzumab 0.3 mg/kg × 3 (D-6 to D-4) (FCC regimen, pediatric) |
| Postgraft immune suppression with CsA alone (3 mg/kg D-1) | |
| Alternative transplantations | |
| MMUD‡ | FLU 30 mg/m2 × 4 (D-6 to D-3), CY 300 mg/m2 × 4 (D-6 to D-3), ATG 3.75 mg/kg × 2 (D-4 to D-3) and TBI 2 Gy (D-1) (FCA TBI regimen) or |
| FLU 30 mg/m2 × 4 (D-6 to D-3), CY 300 mg/m2 × 4 (D-6 to D-3) and alemtuzumab 0.2 mg/kg × 5 (D-7 to D-3) and TBI 2 Gy (D-1) (FCC TBI regimen) | |
| Postgraft immunosuppression as for MRD | |
| CB‡ | FLU 30 mg/m2 × 4 (D-6 to D-3), CY 30 mg/kg × 4 (D-6 to D-3), ATG 2.5 mg/kg × 2 (D-4 to D-3) and TBI 2 Gy (D-1) (French protocol called APCORD) |
| Postgraft immune suppression with CsA alone (3 mg/kg D-1) | |
| Haplo | FLU 30 mg/m2 × 4 (D-6 to D-2), CY 14.5 mg/kg × 2 (D-7 to D-6) and TBI 2 Gy (D-1) (Baltimore protocol) |
| Postgraft immune suppression associate CY 50 mg/kg × 2 (D+3 and D+4), tacrolimus (D+5), and mycophenolate (D+5 to D+35) | |
| Inherited aplastic anemia | |
| Fanconi anemia | |
| MRD | FLU 30 mg/m2 × 3 (D-4 to D-2), CY 10 mg/kg × 4 (D-5 to D-2) |
| Postgraft immune suppression associates CsA (3 mg/kg D-1) and mycophenolate (D+1 to D+45). | |
| MUD‡ | FLU 30 mg/m2 × 4 (D-6 to D-3), CY 10 mg/kg × 4 (D-6 to D-3) and ATG 2.5 mg/kg × 2 (D-4 to D-3) and TBI 2 Gy (D-1) |
| Postgraft immune suppression associates CsA (3 mg/kg D-1) and mycophenolate (D+1 to D+45) | |
| Dyskeratosis congenita | |
| MRD§ | FLU 30 mg/m2 × 5 (D-7 to D-3), CY 60 mg/kg × 2 (D-3 to D-2) and alemtuzumab 0.3 mg/kg × 3 (D-6 to D-4) (FCC regimen, pediatric) |
| Postgraft immune suppression with CsA alone (3 mg/kg D-1) | |
| Management post-HSCT | |
| Early post-HSCT management | Postgraft CsA is continued for at least 9 months followed by tapering to 12 months |
| Blood CsA trough levels is about 250 μg/L | |
| Regular monitoring of unfractionated and lineage-specific CD3 (T-cell) chimerism in peripheral blood and bone marrow is recommended to detect early graft failure. Progressive mixed chimerism predicts a high risk of graft rejection. Stable mixed T-cell chimerism in the presence of full-donor myeloid chimerism is common when using the FCC regimen. | |
| Late effects | Multidisciplinary long-term follow-up is recommended with a comprehensive surveillance for endocrine, metabolic, bone, and cardiovascular risks. Moreover, patients with FA should be systematically seen every 6 months by gynecologists and stomatologists to enable early cancer detection and prompt surgery. |
| Iron overload is easily addressed by regular venesections once patients are fully engrafted post HSCT | |
| Revaccinations follow standard HSCT practice | |
ATG, antithymocyte globulin; CB, cord blood; CsA, cyclosporine; CY, cyclophosphamide; FLU, fludarabine; Haplo, haplo-identical family donor; HSCT, hematopoietic stem cell transplantation; MMUD, mismatched unrelated donor; MRD, matched related donor; MTX, methotrexate; MUD, matched unrelated donor; TBI, total body irradiation.
*
ATG schedule and dosage are presented with thymoglobulin (Genzyme, a Sanofi company).
†
Alternative regimen may be considered in patients >30 years in case of comorbidities.
‡
A single injection of rituximab (150-200 mg/m2) is recommended per day+5 in other than alemtuzumab-based regimens.
§
The regimen we decided to use in Saint-Louis Hôpital (Paris, France).