Table 2.
Clinical characteristics of BCG-complicated patients
| Pt. | Gender/consanguinity | Age at diagnosis/Age at HSCT (months) | Gene/Mutation | Clinical presentation | Pre-HSCT BCG related complications | Pre HSCT anti BCG meds, duration (months) | Pre-HSCT laboratory evaluation cells (μl) | Pre-HSCT laboratory evaluation cells (μl) | Donor match | Graft source | Conditioning | GVHD px | TNC dose (108/kg) | Neut Engrafta (days) | aGVHD (location, grade) | cGVHD, extent, location | Post transplant BCG complication | Anti-BCG tx, duration, months | Last donor chimerism (%) | Outcome, Last follow-up (months) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ANC | ALC | CD3 | CD4 | CD8 | CD19 | NK | Day | Clinical presentationc | Positive cultures, location | Pathology | ||||||||||||||||||
| 1 | F/Yes | 7/8 | RAG1 c.1410_1413delCTTG | FTT, C. diarrhea, Rec. chest infection, Pul. aspergillosis, Pancytopenia | None | None | 300 | 300 | 6 | 6 | 78 | 0 | 195 | MSD | PBSC | None | None | 8.9 | NAb | No | Limited, eye | 30 | Inflammatory, Regional. | Yes, skin | BM:granulomas | INH + RIF + ETM, 8 | 51 | A + W, 105 |
| 2 | F/Yes | 0/6 | DCLRE1C c.815G > T | FTT, Omenn, rec. pneumoniae, CMV, E coli and stenotrophomonas sepsis, pseudomonas OM and cellulitis, candidal infections. | None | None | 1200 | 1000 | 700 | 150 | 260 | 20 | 230 | MRD | PBSC | Flu | CSA | 50 | 17 | Skin I | Limited, skin | 19 | Inflammatory, Regional | Yes, LN | Skin + LN: granuloma, ZN + | INH + RIF + ETM, 12 | 100 | A + W, 59 |
| 3 | M/Yes | 7/12 | IKBKB c.207delC | rec. pneumoniae, thrush | BCGosis (bone marrow, skin, liver, spleen) | INH + RIF + ETM + Cipro, 4 | 1200 | 23,500 | 20,915 | 16,450 | 3760 | 1880 | 1175 | MRD | BM | Flu/Treo/TT/ATG | CSA + MMF | 4.9 | 13 | GI III | No | 5 | Infectious, Diss: Liver, spleen, skin, BM, kidney, CNS | Yes, gast.asp. skin | Liver+ BM +Skin: granuloma, ZN+ | INH + RIF + ETM + Cipro, 16 | 7 | Died of graft failure, diss BCGosis, 17 |
| 4 | F/Yes | 8/9 | IL7Rα c.158G > A | Rec. UTI, thrush, c.diarrhea | BCGosis (lung, GI, liver, retroperitoneum) | INH + RIF + ETM, 1 | 4300 | 200 | 0 | 0 | 0 | 180 | 0 | MSD | BM | Flu/Treo/ATG | CSA | 10.9 | 26 | GI IV | No | 2 | Infectious, Diss: lung, liver, spleen, gi,, endocard | Yes: sput, perit fl, skin | GI: c. mild inflam, no granulomas, ZN+ | ETM + RIF + INH + Doxy + Azythro + Cipro, 8 | 100 | Died, diss BCGosis, 7 |
| 5 | M/Yes | 6/6 | JAK3 c.2680 + 89 C > T | FTT, rec pneumoniae and AOM, cholestatic hepatitis | None | INH + ETM + Cipro, 0.25 | 737 | 1277 | 0 | 0 | 0 | 1200 | 0 | MRD | PBSC | None | CSA + CS | 7.6 | 8 | Skin I | No | 3 | Undetermined, Diss: skin, spleen, liver, eye, CNS, bones, lungs, kidney. | Yes: skin | Skin: mono infilt, no granulomas, ZN+ | ETM + RIF + INH + Cipro/Moxi + Doxy, 24 | 17 | A + W, 60 |
| 6 | F/Yes | 3/5 | RAG1 c.210C > T | FTT, c. diarrhea, Omenn, AOM | None | INH + RIF + ETM, 0.5 | 8400 | 50,400 | NA | NA | NA | NA | NA | MSD | BM | Flu/Treo/TT/ATG | CSA | 9.75 | 16 | No | No | 4 | Undetermined, Diss: LN, skin | No | NA | ETM + INH + Cipro, 18 | 23 | A + W, 17 |
| 7 | M/Yes | 13/15 | PNP c.635 T > G | FTT, rec pneumoniae and AOM, c. diarrhea | None | INH + ETM + Cipro, 0.6 | 17,200 | 200 | 24 | 4 | 6 | 22 | 148 | MSD | BM | Flu/Treo | CSA | 9.76 | 9 | No | No | 23 | Inflammatory, Diss: skin, LN. | Skin, LN: AFB pos.; culture neg. | NA | RIF + INH + ETM + Doxy + Levo, 10.5 | 100 | A + W, 26 |
| 8 | F/Yes | 5/6 | VPS45 c.671C > A | Rec pneumoniae, skin abscesses, CMCC, delayed separation of cord, pancytopenia | None | None | 200 | 3400 | NA | NA | NA | NA | NA | MSD | BM | Bu/Flu/TT/ATG | CSA | 6.91 | 11 | No | No | 40 | Inflammatory, Local | Yes: skin | NA | INH+Cipro, 9 | 100 | A + W, 20 |
| 9 | M/No | 5/14 | IL2RG c.202G > A | FTT, c. diarrhea, CMCC, AOM, maternal engraftment | None | None | 2200 | 4500 | NA | NA | NA | NA | NA | MUD | PBSC | Bu/Flu/Alem | CSA + MMF | 23.6 | 14 | GI I | No | 7 | Undetermined, Diss: LN, skin, liver | Yes: gast. asp., LN | Skin, liver: granulomas, ZN+ | INH + RIF + ETM + Cipro + Azithro, 12 | 100 | A + W, 38 |
| 10 | M/Yes | 4/6 | T-B-NK+ SCID | Rec. pneumoniae. PJP pneumonia, c. diarrhea, rec bacteremiae, Omenn, CMCC | BCGosis (liver, LN) | None | 100 | 700 | 672 | 189 | 504 | 7 | 21 | MMUD | CB | Flu/Treo | CSA + MMF | 2.4 | None | No | No | 55 | Infectious, Diss: Liver, LN | No | NA | Azythro + Amikacin + Cirpo, 3 | NA | Died D + 88, non-engraftment |
| 11 | M/Yes | 3/5 | RAG1 p.Q407E | CMV pneumonia +viremia, PJP pneumonia, Omenn | None | INH + RIF + ETM, 1.5 | 7200 | 1400 | 56 | 56 | 0 | 28 | 1260 | MRD | BM | Flu/Treo/ATG | CSA + MMF | 9.5 | 20 | No | No | 60 | Inflammatory, Local | No | Skin: histiocytes, no granulomas | INH + RIF + ETM, 12 | 100 | A + W, 27 |
| 12 | F/Yes | 103/111 | IL21R p.R201Q | rec AOM, CMV viremia, rec pneumonia, PJP pneumonia, mucosal HSV | None | None | 2800 | 4100 | 3280 | 1968 | 820 | 533 | 82 | MSD | BM | Flu/Treo/TT/ATG | CSA + MMF | 9.69 | 14 | No | No | 36 | Inflammatory, Regional | NA | NA | INH + RIF + ETM + Cipro, 5 | 100 | A + W, 65 |
| 13 | M/No | 5/10 | IL2RG p.R222V | pneumonia, diarrhea | None | None | 2700 | 9200 | 3036 | 1012 | 1840 | 3312 | 2392 | MSD | BM | Flu/Treo/TT/ATG | CSA | 14.6 | 21 | No | No | 25 | Inflammatory, Local | No | NA | INH + RIF + ETM, 5 | 25 | A + W, 47 |
| 14 | F/Yes | 11/12 | STIM1 c.436_437insG | rec pneumoniae, FTT, hypotonia, ectodermal dysplasia, AIHA | None | None | 2890 | 4540 | NA | 2350 | 2350 | 890 | 320 | MSD | BM | Flu/Treo/TT/ATG | CSA + MMF | 8.4 | 21 | No | No | 450 | Infectious, Diss: LN. | Yes: gast asp | LN:hyperplasia, granuloma, ZN+ | INH + RIF + ETM + Cipro, 13, ongoing | 12 | A + W, 27 |
| 15 | F/Yes | 8/10 | JAK3 c.172G > A | Rec. pneumoniae+ AOM diarrhea, ecthyma gangrenosum, pseudomonas bacteremia, Omenn | None | INH + ETM, 1 | 1500 | 800 | 72 | 40 | 40 | 648 | 40 | MRD | BM | Flu/Treo/TT/ATG | CSA + MMF | 9.9 | 40 | No | No | 42 | Inflammatory, Diss: skin, LN. | Yes: gast asp | LN: granuloma, ZN neg | INH + RIF + ETM, 10 ongoing | 20 | A + W,9 |
aNeutrophil engraftment defined as the first day of 3 consecutive days of ANC > 500
bNeutrophil count did not fall below 500 cells/mm3
cExtent of infection was defined as local (injection site) reaction, regional (regional LN, ipsilateral to vaccine site), distant (any single site beyond local/regional), and disseminated (involvement of more than one distant site and/or blood/bone marrow involvement) (4)
a. acute, AIHA autoimmune hemolytic anemia, ALC absolute lymphocyte count, Alem Alemtuzumab, ANC absolute neutrophil count, AOM acute otitis media, ATG antithymoglobulin, A + W alive and well, Azithro Azithromycin, BCG Bacillus Calmette-Guerin, BM bone marrow, Bu busulfan, c. chronic, CB cord blood, Cipro Ciprofloxacin, CMCC chronic mucocutaneous candidiasis, CMV cytomegalovirus, CSA cyclosporin A, Diss disseminated, DLI donor lymphocyte infusion, Doxy Doxycillin, ETM ethambutol, F female, Flu Fludarabine, FTT failure to thrive, GI gastrointestinal, GVHD graft vs host disease, HSCT hemtopoietic stem cell transplantation, INH isoniazid, Levo Levofloxacin, LN lymph node, M male, MMF mycophenolate mofetil, Moxi Moxifloxacin, MMUD mismatched unrelated donor, MRD matched related donor, MSD matched sibling donor, MUD matched unrelated donor, NA non-available, PBSC peripheral blood stem cell, PJP pneumocyctis jirovci, Pt patient. Pul pulmonary, Rec recurrent. RIF Rifampicin, TNC total nucleated cells, Treo Treosulfan, TT thiotepa, ZN Zeihl Neilsen