Clinical course and immune function
| . | Baseline . | DLBCL diagnosis . | Workup and HSCT . | Day 100 post-HSCT . | 1 Year post-HSCT . | 2 Years post-HSCT . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical course | Multiple lung, sinus, and tonsil infections starting at age 1.5 y requiring frequent hospitalizations and antibiotics SCD with HPFH G6PD | Diagnosis: Chest CT with bilateral, extensive lung infiltrates Lung biopsy revealed a DLBCL, EBV+ 2A level lymph nodes, palatine tonsil, ovary involved CSF and bone marrow were negative | Workup (all negative): HIV PCR FISH for DiGeorge Chromosome breakage studies | Grade 2 skin GVHD treated with topical steroids only CMV viremia and possible pneumonia treated with IV immunoglobulin and ganciclovir | Pulmonary actinomyces treated with PCN Bronchiectasis | Clinically well Treatment of actinomyces continues | ||||||||
| Genetic workup (all negative): Rag 1/2 AT mutation analysis Nijmegen Artemis XLP XIAP | ||||||||||||||
| Immune function | ||||||||||||||
| T cell | Numbers (abs): CD3 = 353, CD4 = 118, CD8 = 163 | Numbers (abs): CD3 = 223, CD4 = 128, CD8 = 92 | Numbers (abs): CD3 = 1350, CD4 = 662, CD8 = 688 | Numbers (abs): CD3 = 1089, CD4 = 633, CD8 = 428 | ||||||||||
| TREC (nl >3063): 289 copies/106 CD3 T cells | TREC (nl >3063): 500 copies/106 CD3 T cells | TREC (nl >3063): 3800 copies/106 CD3 T cells | TREC (nl >3063): 6010 copies/106 CD3 T cells | |||||||||||
| Proliferation: Low response (<5% of control) to PHA, absent responses to candida and TT | Treatment: Ritux/pred × 1 cycle Ritux/pred/MTX/Doxo × 2 cycles Ritux/ARAC/MTX × 2 cycles Ritux/Cy/Vinc/pred/MTX/Doxo × 2 cycles Surgical resection of hilar lymph nodes and lung masses Surgical resection of ovary and peritoneal mass | WES Compound heterozygosity for the c.1796+2 T>C mutation and N176S variant in the CDH17 gene Heterozygous variant in the LIG1 gene Homozygous E7V mutation in the HBB gene Heterozygous S188F mutation in the G6PD gene | Proliferation: Normal response to PHA. PWM, candida, and TT not tested. | Proliferation: Normal response to PHA and PWM. Absent responses to candida and TT. | Proliferation: Normal response to PHA and PWM. Candida and TT not tested. | |||||||||
| TCR diversity: Normal | ||||||||||||||
| Subsets (%): | Subsets (%): | Subsets (%): | Subsets (%): | |||||||||||
TNAIVE TCM TEM TEMRA | CD4 33.6 38.7 26.5 1.19 | CD8 4.4 0.05 4.85 90.7 | TNAIVE TCM TEM TEMRA | CD4 — — — — | CD8 2.85 2.5 66 28.7 | TNAIVE TCM TEM TEMRA | CD4 — — — — | CD8 31.7 3.6 19.5 45.2 | TNAIVE TCM TEM TEMRA | CD4 62.2 17.1 18.5 2.13 | CD8 39.4 12.9 33.7 13.9 | |||
| B cell | Numbers (abs): CD19 = 27 | Numbers (abs): CD19 = 100 | Numbers (abs): CD19 = 1058 | Numbers (abs): CD19 = 756 | ||||||||||
| Immunoglobulins*: IgG 1270, IgA 199, IgM 524, IgE <2 | Immunoglobulins†: IgG 494, IgA 27, IgM 328, IgE <2 | Immunoglobulins: IgG 3180, IgA 89, IgM 136, IgE 4 | Immunoglobulins: IgG 1310, IgA 123, IgM 124, IgE 3 | |||||||||||
| Vaccine titers: Tetanus Ab 0.06 (minimally protective), diphtheria Ab 0.06 (minimally protective), minimal response to all S.pneumo serotypes | Response: Mixed response to chemotherapy regimens NED at the time of HSCT | HSCT details: MSD HSCT (sibling had normal lymphocyte counts, no SCD or G6PD) Cy/TBI 1320cGy preparative regimen CSA/MTX for GVHD prophylaxis | Vaccine titers: Tetanus Ab 0.21 (protective), diphtheria Ab 0.21 (protective), protective response to 9 of 14 S.pneumo serotypes. | |||||||||||
| NK cell | Numbers (abs): CD16/56 = 526 | Numbers (abs): CD16/56 = 72 | Numbers (abs): CD16/56 = 185 | Numbers (abs): CD16/56 = 120 | ||||||||||
| Activity: Normal | Activity: Normal | Activity: Decreased | Activity: Normal | |||||||||||
| Chimerism | 100% Donor chimerism in peripheral blood and bone marrow | 100% Donor chimerism in peripheral blood and bone marrow | 100% Donor chimerism in peripheral blood and bone marrow | |||||||||||
| . | Baseline . | DLBCL diagnosis . | Workup and HSCT . | Day 100 post-HSCT . | 1 Year post-HSCT . | 2 Years post-HSCT . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical course | Multiple lung, sinus, and tonsil infections starting at age 1.5 y requiring frequent hospitalizations and antibiotics SCD with HPFH G6PD | Diagnosis: Chest CT with bilateral, extensive lung infiltrates Lung biopsy revealed a DLBCL, EBV+ 2A level lymph nodes, palatine tonsil, ovary involved CSF and bone marrow were negative | Workup (all negative): HIV PCR FISH for DiGeorge Chromosome breakage studies | Grade 2 skin GVHD treated with topical steroids only CMV viremia and possible pneumonia treated with IV immunoglobulin and ganciclovir | Pulmonary actinomyces treated with PCN Bronchiectasis | Clinically well Treatment of actinomyces continues | ||||||||
| Genetic workup (all negative): Rag 1/2 AT mutation analysis Nijmegen Artemis XLP XIAP | ||||||||||||||
| Immune function | ||||||||||||||
| T cell | Numbers (abs): CD3 = 353, CD4 = 118, CD8 = 163 | Numbers (abs): CD3 = 223, CD4 = 128, CD8 = 92 | Numbers (abs): CD3 = 1350, CD4 = 662, CD8 = 688 | Numbers (abs): CD3 = 1089, CD4 = 633, CD8 = 428 | ||||||||||
| TREC (nl >3063): 289 copies/106 CD3 T cells | TREC (nl >3063): 500 copies/106 CD3 T cells | TREC (nl >3063): 3800 copies/106 CD3 T cells | TREC (nl >3063): 6010 copies/106 CD3 T cells | |||||||||||
| Proliferation: Low response (<5% of control) to PHA, absent responses to candida and TT | Treatment: Ritux/pred × 1 cycle Ritux/pred/MTX/Doxo × 2 cycles Ritux/ARAC/MTX × 2 cycles Ritux/Cy/Vinc/pred/MTX/Doxo × 2 cycles Surgical resection of hilar lymph nodes and lung masses Surgical resection of ovary and peritoneal mass | WES Compound heterozygosity for the c.1796+2 T>C mutation and N176S variant in the CDH17 gene Heterozygous variant in the LIG1 gene Homozygous E7V mutation in the HBB gene Heterozygous S188F mutation in the G6PD gene | Proliferation: Normal response to PHA. PWM, candida, and TT not tested. | Proliferation: Normal response to PHA and PWM. Absent responses to candida and TT. | Proliferation: Normal response to PHA and PWM. Candida and TT not tested. | |||||||||
| TCR diversity: Normal | ||||||||||||||
| Subsets (%): | Subsets (%): | Subsets (%): | Subsets (%): | |||||||||||
TNAIVE TCM TEM TEMRA | CD4 33.6 38.7 26.5 1.19 | CD8 4.4 0.05 4.85 90.7 | TNAIVE TCM TEM TEMRA | CD4 — — — — | CD8 2.85 2.5 66 28.7 | TNAIVE TCM TEM TEMRA | CD4 — — — — | CD8 31.7 3.6 19.5 45.2 | TNAIVE TCM TEM TEMRA | CD4 62.2 17.1 18.5 2.13 | CD8 39.4 12.9 33.7 13.9 | |||
| B cell | Numbers (abs): CD19 = 27 | Numbers (abs): CD19 = 100 | Numbers (abs): CD19 = 1058 | Numbers (abs): CD19 = 756 | ||||||||||
| Immunoglobulins*: IgG 1270, IgA 199, IgM 524, IgE <2 | Immunoglobulins†: IgG 494, IgA 27, IgM 328, IgE <2 | Immunoglobulins: IgG 3180, IgA 89, IgM 136, IgE 4 | Immunoglobulins: IgG 1310, IgA 123, IgM 124, IgE 3 | |||||||||||
| Vaccine titers: Tetanus Ab 0.06 (minimally protective), diphtheria Ab 0.06 (minimally protective), minimal response to all S.pneumo serotypes | Response: Mixed response to chemotherapy regimens NED at the time of HSCT | HSCT details: MSD HSCT (sibling had normal lymphocyte counts, no SCD or G6PD) Cy/TBI 1320cGy preparative regimen CSA/MTX for GVHD prophylaxis | Vaccine titers: Tetanus Ab 0.21 (protective), diphtheria Ab 0.21 (protective), protective response to 9 of 14 S.pneumo serotypes. | |||||||||||
| NK cell | Numbers (abs): CD16/56 = 526 | Numbers (abs): CD16/56 = 72 | Numbers (abs): CD16/56 = 185 | Numbers (abs): CD16/56 = 120 | ||||||||||
| Activity: Normal | Activity: Normal | Activity: Decreased | Activity: Normal | |||||||||||
| Chimerism | 100% Donor chimerism in peripheral blood and bone marrow | 100% Donor chimerism in peripheral blood and bone marrow | 100% Donor chimerism in peripheral blood and bone marrow | |||||||||||
Ab, antibody; abs, absolute; ARAC, cytarabine; AT, ataxia telangiectasia; CMV, cytomegalovirus; CSA, cyclosporine; CSF, cerebrospinal fluid; CT, computed tomography; Cy, cytoxan; DLBCL, diffuse large B-cell lymphoma; Doxo, doxorubicin; EBV, Epstein-Barr virus; FISH, florescence in situ hybridization; G6PD, glucose 6-phosphate deficiency; GVHD, graft-versus-host disease; HBB, β hemoglobin; HPFH, hereditary persistence of fetal hemoglobin; MSD, matched sibling donor; MTX, methotrexate; NED, no evidence of disease; PCN, penicillin; PCR, polymerase chain reaction; PHA, phytohemagglutinin; pred, prednisone; PWM, pokeweed mitogen; Ritux, rituximab; SCD, sickle-cell disease; TBI, total body irradiation; TCM, central memory T cells; TEM, effector memory T cells; TEMRA, effector memory T cells that express CD45RA; TNAIVE, naïve T cells; TT, tetanus toxoid; Vinc, vincristine; WES, whole exome sequencing; XIAP, X-linked inhibitor of apoptosis; XLP, X-linked lymphoproliferative disorder.
Previous IV immunoglobulin replacement therapy is uncertain.
Last IV immunoglobulin infusion 1 month prior.