Clinical and immunologic characteristics of CHH patients
| Patient no. . | Sex . | Mutation . | Clinical characteristics . | Presence before HSCT . | Age at transplantation, y . | Donor . | Conditioning . | Graft stability at last control . | Transplant-related complication . | Outcome . | Follow-up, y . | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Autoimmunity . | BM failure . | Organ sequlae . | Up to 1 y after HSCT . | Beyond 1 y after HSCT . | ||||||||||
| 1 | F | 12-25 dup/+post(STOP)T | Omenn syndrome | No | No | No | < 1 (8 mo) | MSD | Busulfan/cyclophosphamide | 90% donor on T cells30% donor on B cells70% on myeloid cells | None | None | Alive and well | 11 |
| 2 | F | A214T/G146A | Omenn syndrome | No | No | No | < 1 (8 mo) | Haploidentical father | Busulfan/cyclophosphamide | 100% donor on lymphocytes100% recipient on myeloid cells | None | Severe autoimmune thrombopenia leading to cerebral hemorrhage; CMV primoinfection with lung disease hemorrhage | Died 4 y after HSCT due to autoimmunity | 4 |
| 3 | F | 40G>A/+63C>T | Chronic intractable diarrhea with failure to thrive | Autoimmune enteropathy | Yes, transient | No | 1.9 | MUD | Busulfan/cyclophosphamide | Donor chimerism 100% (whole blood) | EBV-lymphoproliferative disorder | None | Alive and well | 8.5 |
| 4 | M | n.a. | Adenovirus hepatitis; failure to thrive | No | Yes | Yes, liver function disorder due to adenovirus hepatitis | 2.3 | Haploidentical mother | Busulfan/fludarabine | n.a. | Engraftment failure; Klebsiella sepsis; generalized adenovirus infection | n.a. | Died 6 mo after HSCT due to adenovirus infection | n.a |
| 5 | F | g-25_11trip/g.96_97dup | Multiple bacterial pneumonias; varicella pneumonitis; growth hormone deficiency | Yes, autoimmune hemolytic anemia | No | Yes, lung bronchiectasis | 2.5 | MSD | Busulfan/cyclophosphamide | 100% donor (whole blood) | None | None(growth hormone deficiency treated? growth hormone insufficiency substitution) | Alive and well | 16 |
| 6 | M | n.a. | Recurrent lung infections | No | No | Yes, lung bronchiectasis | 2.5 | Haploidentical father | Busulfan/fludarabine/Thiotepa | n.a. | Engraftment failure; generalized adenovirus infection | n.a. | Died 7 mo after HSCT due to adenovirus infection | n.a. |
| 7 | M | 0-4 dup/−13-22tripl | Recurrent fungal infections; chronic diarrhea with failure to thrive | No | No | No | 2.5 | MUD | Busulfan/cyclophosphamide | 100% donor chimerism (whole blood) | Acute GVHD grade II | Acute nephritis: 6 y post-HSCT | Alive and well | 7 |
| 8 | F | 35C>7/70A>G | Pure red cell aplasia | Yes, erythrodermia | Yes | No | 2.5 | MUD | Busulfan/cyclophosphamide | 100% donor (whole blood) | Mild veno-occlusive disease; mild acute GVHD | Pneumococcus sepsis | Died 29 mo after HSCT due to pneumococcus sepsis | 2.5 |
| 9 | M | Homozygous 70 A>G | Persistent EBV viremia | No | No | No | 2.6 | MSD | Busulfan/cyclophosphamide | 100% donor (blood) | None | None | Alive and well | 2.5 |
| 10 | F | insT195/C63T | Several pneumonias and chronic diarrhea; development of aplastic anemia | No | Yes, aplastic anemia; no virus was found as etiology | No | 3 | MSD | Busulfan/cyclophosphamide | 100% donor (whole blood: mononuclear cells, granulocytes) | None | None | Alive and well | 12 |
| 11 | F | 154 G>C | Persistent infection with EBV, herpes simplex virus, and CMV | No | No | Bilateral interstitial pneumonitis and bronchiectasis on high-resolution computed tomography | 3.5 | mMUD | Campath/treosulfan/cyclophosphamide | 100% donor (whole blood) | Pulmonary hemorrhage and multiorgan failure leading to death at day +32 | n.a. | n.a. | |
| 12 | F | Homozygous 70 A>G | Persistent EBV viremia; Adenovirus enteritis; HHV-6 viremia infection of the gut with small round structured virus | No | Yes, EBV-related red cell aplasia | No | 4.5 | MUD | Busulfan/cyclophosphamide | Donor chimerism94% on T cells, 90% on B cells, 76% on myeloid cells | Pneumonitis; HHV-6 infection | None | Alive and well | 7 |
| 13 | M | g.-20_4dup/g.4C>T | Chronic lung and ear infections; intestinal malabsorption with severe failure to thrive; growth hormone deficiency | Yes, autoimmune hemolytic anemia, autoimmune hypothyroidism, and autoimmune enteropathy | No | Yes, lung bronchiectasis | 5.9 | MUD | Busulfan/fludarabine | Donor chimerism 94% on mononuclear cells, 80% on neutrophils | Cutaneous candida infection; BK viremia | Persisting growth hormone deficiency (substituted) | Alive and well | 5 |
| 14 | F | n.a. | Severe varicella infection; failure to thrive; EBV-related large B cell lymphoma with central nervous system compromise | Yes, severe eczema | Yes, transient | No | 11 | MUD | Fludarabine/melphalan | n.a. | Gram-positive sepsis; lung aspergillosis; hemorrhagic cystitis due to BK virus | None | Alive and well | 4 |
| 15 | M | 4C>T/13db dup | Chronic diarrhea; persistent EBV infection; chronic human papillomavirus infection; chronic granulomatous ulcerative skin lesions | No | No | Yes, chronic interstitial pneumonitis and bronchiectasis with oxygen needed at night | 16.8 | MUD | Fludarabine/melphalan | n.a. | Mild cutaneous GVHD | None | Alive and well | 1.6 |
| 16 | F | n.a. | Severe varicella infection; EBV-related non-Hodgkin lymphoma; chronic granulomatous ulcerative skin lesions | No | Yes, CMV-related infection | Yes, lung bronchiectasis secondary to varicella pneumonitis and primary lung lymphoma | 19 | MSD | Busulfan/cyclophosphamide | 100% donor (whole blood) | Lung aspergillosis and candidiasis; CMV gastrointestinal disease; sinocerebral mucormycosis | None | Died 10 mo after HSCT due to cerebral mucormycosis | n.a. |
| Patient no. . | Sex . | Mutation . | Clinical characteristics . | Presence before HSCT . | Age at transplantation, y . | Donor . | Conditioning . | Graft stability at last control . | Transplant-related complication . | Outcome . | Follow-up, y . | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Autoimmunity . | BM failure . | Organ sequlae . | Up to 1 y after HSCT . | Beyond 1 y after HSCT . | ||||||||||
| 1 | F | 12-25 dup/+post(STOP)T | Omenn syndrome | No | No | No | < 1 (8 mo) | MSD | Busulfan/cyclophosphamide | 90% donor on T cells30% donor on B cells70% on myeloid cells | None | None | Alive and well | 11 |
| 2 | F | A214T/G146A | Omenn syndrome | No | No | No | < 1 (8 mo) | Haploidentical father | Busulfan/cyclophosphamide | 100% donor on lymphocytes100% recipient on myeloid cells | None | Severe autoimmune thrombopenia leading to cerebral hemorrhage; CMV primoinfection with lung disease hemorrhage | Died 4 y after HSCT due to autoimmunity | 4 |
| 3 | F | 40G>A/+63C>T | Chronic intractable diarrhea with failure to thrive | Autoimmune enteropathy | Yes, transient | No | 1.9 | MUD | Busulfan/cyclophosphamide | Donor chimerism 100% (whole blood) | EBV-lymphoproliferative disorder | None | Alive and well | 8.5 |
| 4 | M | n.a. | Adenovirus hepatitis; failure to thrive | No | Yes | Yes, liver function disorder due to adenovirus hepatitis | 2.3 | Haploidentical mother | Busulfan/fludarabine | n.a. | Engraftment failure; Klebsiella sepsis; generalized adenovirus infection | n.a. | Died 6 mo after HSCT due to adenovirus infection | n.a |
| 5 | F | g-25_11trip/g.96_97dup | Multiple bacterial pneumonias; varicella pneumonitis; growth hormone deficiency | Yes, autoimmune hemolytic anemia | No | Yes, lung bronchiectasis | 2.5 | MSD | Busulfan/cyclophosphamide | 100% donor (whole blood) | None | None(growth hormone deficiency treated? growth hormone insufficiency substitution) | Alive and well | 16 |
| 6 | M | n.a. | Recurrent lung infections | No | No | Yes, lung bronchiectasis | 2.5 | Haploidentical father | Busulfan/fludarabine/Thiotepa | n.a. | Engraftment failure; generalized adenovirus infection | n.a. | Died 7 mo after HSCT due to adenovirus infection | n.a. |
| 7 | M | 0-4 dup/−13-22tripl | Recurrent fungal infections; chronic diarrhea with failure to thrive | No | No | No | 2.5 | MUD | Busulfan/cyclophosphamide | 100% donor chimerism (whole blood) | Acute GVHD grade II | Acute nephritis: 6 y post-HSCT | Alive and well | 7 |
| 8 | F | 35C>7/70A>G | Pure red cell aplasia | Yes, erythrodermia | Yes | No | 2.5 | MUD | Busulfan/cyclophosphamide | 100% donor (whole blood) | Mild veno-occlusive disease; mild acute GVHD | Pneumococcus sepsis | Died 29 mo after HSCT due to pneumococcus sepsis | 2.5 |
| 9 | M | Homozygous 70 A>G | Persistent EBV viremia | No | No | No | 2.6 | MSD | Busulfan/cyclophosphamide | 100% donor (blood) | None | None | Alive and well | 2.5 |
| 10 | F | insT195/C63T | Several pneumonias and chronic diarrhea; development of aplastic anemia | No | Yes, aplastic anemia; no virus was found as etiology | No | 3 | MSD | Busulfan/cyclophosphamide | 100% donor (whole blood: mononuclear cells, granulocytes) | None | None | Alive and well | 12 |
| 11 | F | 154 G>C | Persistent infection with EBV, herpes simplex virus, and CMV | No | No | Bilateral interstitial pneumonitis and bronchiectasis on high-resolution computed tomography | 3.5 | mMUD | Campath/treosulfan/cyclophosphamide | 100% donor (whole blood) | Pulmonary hemorrhage and multiorgan failure leading to death at day +32 | n.a. | n.a. | |
| 12 | F | Homozygous 70 A>G | Persistent EBV viremia; Adenovirus enteritis; HHV-6 viremia infection of the gut with small round structured virus | No | Yes, EBV-related red cell aplasia | No | 4.5 | MUD | Busulfan/cyclophosphamide | Donor chimerism94% on T cells, 90% on B cells, 76% on myeloid cells | Pneumonitis; HHV-6 infection | None | Alive and well | 7 |
| 13 | M | g.-20_4dup/g.4C>T | Chronic lung and ear infections; intestinal malabsorption with severe failure to thrive; growth hormone deficiency | Yes, autoimmune hemolytic anemia, autoimmune hypothyroidism, and autoimmune enteropathy | No | Yes, lung bronchiectasis | 5.9 | MUD | Busulfan/fludarabine | Donor chimerism 94% on mononuclear cells, 80% on neutrophils | Cutaneous candida infection; BK viremia | Persisting growth hormone deficiency (substituted) | Alive and well | 5 |
| 14 | F | n.a. | Severe varicella infection; failure to thrive; EBV-related large B cell lymphoma with central nervous system compromise | Yes, severe eczema | Yes, transient | No | 11 | MUD | Fludarabine/melphalan | n.a. | Gram-positive sepsis; lung aspergillosis; hemorrhagic cystitis due to BK virus | None | Alive and well | 4 |
| 15 | M | 4C>T/13db dup | Chronic diarrhea; persistent EBV infection; chronic human papillomavirus infection; chronic granulomatous ulcerative skin lesions | No | No | Yes, chronic interstitial pneumonitis and bronchiectasis with oxygen needed at night | 16.8 | MUD | Fludarabine/melphalan | n.a. | Mild cutaneous GVHD | None | Alive and well | 1.6 |
| 16 | F | n.a. | Severe varicella infection; EBV-related non-Hodgkin lymphoma; chronic granulomatous ulcerative skin lesions | No | Yes, CMV-related infection | Yes, lung bronchiectasis secondary to varicella pneumonitis and primary lung lymphoma | 19 | MSD | Busulfan/cyclophosphamide | 100% donor (whole blood) | Lung aspergillosis and candidiasis; CMV gastrointestinal disease; sinocerebral mucormycosis | None | Died 10 mo after HSCT due to cerebral mucormycosis | n.a. |
CHH was established on classical clinical features in all but 2 study patients.
AIHA indicates autoimmune hemolytic anemia; HHV-6, human herpesvirus type 6; mMUD, mismatched MUD; MSD, matched sibling donor; and n.a., not available.