Table 3.
Transplant Characteristics and Outcomes
| Patient No. | 1 | 2 | 3 | 4 | 5 |
|---|---|---|---|---|---|
| Gene involved | SAMD9 (MIRAGE syndrome) | SAMD9 (MIRAGE syndrome) | SAMD9 | SAMD9 | SAMD9 (MIRAGE syndrome) |
| Age at HCT, years | 6.7 | 1.4 | 3.3 | 5 | 1.2 |
| Interval from diagnosis to HCT, years | 6.5 | 0.4 | 0.2 | 0.2 | 0.4 |
| Indication for HCT | Presumed congenital amegakaryocytic thrombocytopenia | MDS | MDS | MDS | MDS |
| Significant pretransplant issues | Secretory diarrhea, adrenocortical insufficiency, lung disease, CKD, failure to thrive | Esophageal achalasia, gastroesophageal reflux, diarrhea, failure to thrive | – | – | Diarrhea. Failure to thrive. |
| Donor type | HLA-identical sibling, female, bone marrow | Unrelated, 10/10 allele match, male, bone marrow | Unrelated, 8/8 allele match, female, bone marrow | Unrelated, 8/8 allele match, male, bone marrow | Father, 5/10 allele match, bone marrow |
| Conditioning regimen; GVHD prophylaxis | Flu/Cy/ATG; Tac/MMF | Bu/Flu/ATG; Tac/Mtx | Bu/Cy/ATG; CsA/Mtx | Bu/Cy/ATG; CsA/Mtx | Bu/Flu; posttransplant Cy, Tac/MMF |
| Conditioning intensity (MA / RIC) | RIC | MA | MA | MA | MA |
| Neutrophil engraftment, days+ | 13 | 12 | 16 | 19 | 14 |
| Platelet engraftment, days+ | 16 | 30 | 14 | 15 | 40 |
| Posttransplant course | Temperature & blood pressure instability, electrolyte imbalance, dehydration, hypoxia | TMA, recurrent pericardial effusions, hypoxia | VOD of liver | Pericardial effusion | TMA, pericardial effusion, VOD of liver |
| Intensive care | Severe hypertension | No | Respiratory distress, did not require intubation | Respiratory distress, required intubation | Respiratory failure, did not require intubation |
| Acute GVHD / Chronic GVHD | No / No | No / Yes | No / No | No / No | No / No |
| Chimerism | 99% donor | 100% donor | 100% donor | 99% donor | 100% donor |
| Post-HCT hematologic outcome | Normal blood counts, no monosomy 7 | Normal blood counts, no monosomy 7, resolution of MDS | Resolution of MDS, no chr. 7 finding | Resolution of MDS, no chr. 7 findings | Normal blood counts, no monosomy 7, resolution of MDS |
| Survival status | Alive; 2.4 y post-HCT | Alive; 3.8 y post-HCT | Alive; 3.2 y post-HCT | Alive; 3 y post-HCT | Alive; 1.4 y post-HCT |
| Current health status | Secretory diarrhea, enteral feeds, low weight and height, thriving, developmental delay, CKD, hypertension, adrenal insufficiency | Recurrent aspiration pneumonias, chronic lung disease, malnutrition, diarrhea, developmental delay, thriving, adrenal insufficiency | School performance issues | Learning disabilities | Supplemental feeds, hypoglycemia episodes, diarrhea, low weight and height, thriving, developmentally delay |
| Patient No. | 6 | 7 | 8 | 9 | 10 |
| Gene involved | SAMD9 (MIRAGE syndrome) | SAMD9L | SAMD9L | SAMD9L | SAMD9L |
| Age at HCT, years | 7.8 | 12.8 | 2.3 | 8.3 | 2 |
| Interval from diagnosis to HCT, years | 5.5 | 0.2 | 1.4 | 0.2 | 1.3 |
| Indication for HCT | MDS | Presumed dyskeratosis congenita | MDS | MDS | MDS |
| Significant pretransplant issues | Hypertension, chronic kidney disease, asthma | Obesity (BMI 34, >97th percentile for age) | Obesity (BMI 27, >97th percentile for age) | – | HLH therapy. E. coli sepsis, pancolitis, ecthyma gangrenosum, aspergillus and candida sepsis |
| Donor type | Unrelated, 10/10 allele match, male, bone marrow | Unrelated double cord blood, male (5/6 allele match), female (5/6 allele match) | Unrelated cord blood, 6/6 allele match, female | HLA-identical sibling, female, bone marrow | Unrelated, 9/10 allele match, bone marrow |
| Conditioning regimen; GVHD prophylaxis | Flu/Mel/Alemtuzumab; Tac/MMF | Flu/Mel/Alemtuzumab; Tac/MMF | Flu/Cy/TBI; CsA/MMF | Cy/TBI/Ara-C | Bu/Cy/ATG |
| Conditioning intensity (MA / RIC) | RIC | RIC | MA | MA | MA |
| Neutrophil engraftment, days+ | 19 | No | 13 | 17 | 18 |
| Platelet engraftment, days+ | 19 | No | 12 | 31 | No |
| Posttransplant course | Blood pressure instability, electrolyte imbalance, fevers, hypoxia | Restrictive lung disease | Parainfluenza with respiratory failure, renal dysfunction | Culture negative sepsis, bleeding gastric ulcer, hemorrhagic cystitis | Coronavirus respiratory tract infection, VOD of liver with respiratory failure, defibrotide, diffuse alveolar hemorrhage |
| Intensive care | No | No | Respiratory failure | Systemic inflammatory response syndrome | Respiratory failure, required intubation |
| Acute GVHD / Chronic GVHD | No / No | No / No | Yes (Grade II, GI, resolved)/No | No / No | Not evaluable / Not evaluable |
| Chimerism | 98% donor | 0% donor | 99% donor | 100% donor | Not done |
| Post-HCT hematologic outcome | Normal blood counts | Graft failure | Resolution of MDS, no chr. 7 finding | Resolution of MDS, no chr. 7 finding | Neutrophil engraftment. Bone marrow not assessed |
| Survival status | Alive; 4.1 y post-HCT | Died of refractory AML; 1.1 y post-HCT | Alive; 2.3 y post-HCT | Alive; 14.7 y post-HCT | Died at day +23 post-HCT from complications related to VOD of liver |
| Current health status | Adrenal insufficiency, diarrhea, hypotension, CKD, urethrocutaneous fistula, developmental delay, thriving | N.A. | CKD | Doing well | N.A. |
| Patient No. | 11 | 12 | |||
| Gene involved | SAMD9L | SAMD9L | |||
| Age at HCT, years | 2.1 | 1.8 | |||
| Interval from diagnosis to HCT, years | 0.5 | 0.5 | |||
| Indication for HCT | MDS | MDS | |||
| Significant pretransplant issues | Otitis media, croup, roseola | Alpha hemolytic streptococcal sepsis | |||
| Donor type | Unrelated, 10/10 allele match, female, bone marrow | Unrelated, 10/10 allele match, female, bone marrow | |||
| Conditioning regimen; GVHD prophylaxis | Bu/Cy; Tac/Mtx | Bu/Cy; Tac/Mtx | |||
| Conditioning intensity (MA / RIC) | MA | MA | |||
| Neutrophil engraftment, days+ | 19 | 9 | |||
| Platelet engraftment, days+ | 17 | 12 | |||
| Posttransplant course | Uneventful | VOD of liver, hemolysis, coagulopathy | |||
| Intensive care | No | VOD | |||
| Acute GVHD / Chronic GVHD | Yes (Grade II, skin, gut, resolved) / Yes skin, mild | No / No | |||
| Chimerism | 100% donor | 100% donor | |||
| Post-HCT hematologic outcome | Normal blood counts, no monosomy 7, resolution of MDS | Normal blood counts, no monosomy 7, resolution of MDS | |||
| Survival status | Alive; 5.3 y post-HCT | Alive; 1.3 y post-HCT | |||
| Current health status | Doing well | Doing well | |||
Abbreviations: ATG (anti-thymocyte globulin); Ara-C (cytosine arabinoside); BU (busulfan); BMI (body mass index); Chr. 7 (chromosome 7); CKD (chronic kidney disease); Cy (cyclophosphamide); CsA (cyclosporine A); GI (gastrointestinal); Flu (fludarabine); HLH (hemophagocytic lymphohistiocytosis); MA (myeloablative); MDS (myelodysplastic syndrome); Mel (melphalan); MIRAGE syndrome (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy); MMF (mycophenolate mofetil); Mtx (methotrexate); N.E. (not evaluable); RIC (reduced intensity conditioning); Tac (tacrolimus); TBI (total body irradiation); TMA (thrombotic microangiopathy); and VOD (veno-occlusive disease)