Table 2.
Diamond Blackfan anemia
| PRE-HCT CHARACTERISTICS | PATIENT #4 | PATIENT #5 | PATIENT #6 | PATIENT #7 |
|---|---|---|---|---|
| Age at diagnosis/at HCT (yr) | 0.3 / 6.1 | 1.2 / 12.2 | 0.1 / 21.9 | 0.1 / 2.3 |
| Patient sex | Male | Female | Female | Female |
| Genetic mutation | None | None | None | RPS19 Heterozygous: c357-2A>G (splicing) |
| Failed steroids | Yes | Initial steroid response, 10 yr remission | Yes | Yes |
| Clinical features | Autism, Neonatal intracerebral hemorrhage, GH deficiency, Hypogonadotropic hypogonadism, Bicuspid aortic valve | − | Hypothyroidism, Bicuspid aortic valve | Anterior ectopic anus |
| Iron | ||||
| Ferritin ng/mL | 342 | 674 | 1643 | 1215 |
| T2* MRI‡ | Hepatic: 3.36 Myocardial: 16.4 | Hepatic: 10.3 Myocardial: ND | Hepatic: 9.7 Myocardial: 41 | Hepatic: 1.9 Myocardial: 45–69 |
| Liver biopsy | Slight to moderate hemosiderosis, septal fibrosis (Batts & Ludwig, grade 2–3, stage 3) | None | 4+ iron, mild to moderate portal fibrosis | None |
| Augmented HCT/CI | 1 | 0 | 5 | 0 |
| Peripheral blood counts | ||||
| ANC (cells/µL) | 960 | 2540 | 2440 | 430 |
| Hematocrit | 23% | 25% | 24% | 24% |
| Platelet count (cells/µL) | 180,000 | 382,000 | 60,000 | 238,000 |
| Transfusion dependent | Yes (pRBC) | Yes (pRBC) | Yes (pRBC) | Yes (pRBC) |
| Bone marrow evaluation | ||||
| Morphology | Marked erythroid hypoplasia, slight myelofibrosis | Moderate erythroid hypoplasia, mild erythroid atypia | Erythroid aplasia, no dysplasia | Erythroid aplasia, no dysplasia |
| Cellularity | 85% | 60–70% | 20–30% | 40% |
| Cytogenetics | Normal | Normal | Normal | Normal |
| Indication for HCT | pRBC transfusion dependent, iron overload (on Exjade and desferol) | pRBC transfusion dependent | pRBC transfusion dependent, iron overload (on Exjade) | pRBC transfusion dependent, iron overload (on Exjade and desferol), Neutropenic despite G-CSF, frequent infections |
| HCT Characteristics and Outcomes | ||||
| Donor/Stem cell source | MURD/marrow | MURD/marrow | MURD/marrow | MURD/marrow |
| Follow-up (yr) | Alive, 4.5 | Alive, 4.0 | Alive, 3.0 | Alive, 0.3 |
| Donor chimerism (CD3+/CD33+)† | 100%/100% | 39%/34% | 96%/100% | 100%/100% |
| GVHD§ | ||||
| Acute/Chronic (Yes/No) | Yes/Yes | Yes/No | No/No | Yes/No |
| Day Immune Suppression Stopped | 1432 | 392 | 198 | Still on |
| Peripheral blood counts† | ||||
| ANC (cells/µL) | 14,421 | 4570 | 4770 | 7280 |
| Hematocrit | 34.9% | 39% | 42% | 37% |
| Platelet count (cells/µL) | 336,000 | 187,000 | 215,000 | 82,000 |
| Bone marrow evaluation† | ||||
| Morphology / cellularity | Trilineage hematopoiesis, 30–40% | ND/ND | ND/ND | N/A/N/A |
| Cytogenetics | Normal | ND | ND | Normal |
| Disease response | Normal hemoglobin, Transfusion independent | Normal hemoglobin, Transfusion independent | Normal hemoglobin, Transfusion independent | Normal hemoglobin, Transfusion independent, Resolution of neutropenia |
†
at last time point studied;
‡
Hepatic T2* mg Iron/g dry weight hepatic tissue, Myocardial T2*: msec;
§
Acute grade II-IV GVHD, delayed acute GVHD or NIH chronic GVHD
Abbreviations: ANC, absolute neutrophil count; DBA, Diamond-Blackfan anemia; GH deficiency, growth hormone deficiency; HCT, hematopoietic cell transplantation; HCT-CI, hematopoietic cell transplantation comorbidity index; MURD, matched unrelated donor; N/A, not available; ND, not done; pRBC, packed red blood cell; R, recipient; vs, versus; yr, years