Table 1.
Summary of B cell lymphomas in PIDDs.
| PID | References | N | Proposed mechanism | Cancer | Specific mutations | Age/sex | Manifestation/course | Treatment | Outcome |
|---|---|---|---|---|---|---|---|---|---|
| IMMUNODEFICIENCIES AFFECTING CELLULAR AND HUMORAL IMMUNITY | |||||||||
| Coronin 1a deficiency* | (13) | 2 | EBV associated | Pt1: DLBCL | Coronin-1a mutation: V134M/V134M | 1/M | Left orbit mass | Chemotherapy | F/U at 11.5 y = CR |
| Pt2: DLBCL | Coronin-1a mutation: V134M/V134M | 0.6/F | Cervicothoracoabdominal LN and cerebral lesion | Chemotherapy | Died during induction therapy at 8.5 m of age | ||||
| DNA Ligase IV mutation* | (14) | 1 | EBV associated | DLBCL | LigIV gene: M249V substitution and a 5 nucleotide del from 1,270–1,274 | 14/F | Progressive gingival swelling and high fever | Vincristine, cyclophosphamide, and prednisolone | Died of respiratory aspergillosis |
| Artemis-SCID* | (15) | 1 | DNA repair defect | BCL | Hypomorphic mutations of the Artemis gene | 5/F | Liver, lung, LN, skeletal muscle involvement | Rituximab | Died of lymphoma |
| RAG 1 mutation* | (16) | 1 | NR | DLBCL | RAG1 gene: Allele 1 R314W* Allele 2 R507W/R737H | 2/F | Tumor of right tonsil | Rituximab, HSCT | CR |
| DNA Ligase IV mutation* | (17) | 1 | DNA repair defect EBV associated | DLBCL | Compound heterozygous for a null allele and a hypomorphic mutation in DNA LigIV | 2/F | High fever, cervical LN, hepatomegaly, necrotizing mucositis. | Chemotherapy | Pt. died of aspergillosis |
| ZAP70 deficiency* | (18) | 1 | EBV associated | DLBCL | Zap70 Gene: c.836_837 delAT | 1/F | Generalized lymphadenopathy | Vincristine, cyclophosphamide methylprednisolone | Died of DIC, multiorgan failure |
| ADA deficiency* | (19) | 1 | EBV associated | BCL | NR | NR | NR | NR | Dead 1 week later |
| ADA deficiency | (20) | 1 | EBV associated (suspected) | Immunoblastic plasmacytoid | NR | NR | NR | NR | Died at 4 y |
| ADA deficiency | (21) | 1 | NS | DLBCL | A83D; Exon5 splice donor site c.573 + 1G>A | 10/M | 6-week history of head- ache, eye deviation, and weakness. | COP + APO + 6-MP; MTX | Died after 5 m |
| ADA deficiency | (22) | 1 | Immune dysregulation | BL | Homozygous Q3X | 14/F | Right hip pain and limping | Chemotherapy | CR 20 m later |
| ADA deficiency | (23) | 1 | Immune dysregulation | DLBCL | Homozygous W272X (c.815G > A) | 3/F | Respiratory complaints and symptoms | BFM 2004 protocol | Died of septic shock and intracranial hemorrhage after starting treatment |
| ADA deficiency* | (24) | 1 | EBV associated | Plasmablastic | Homozygous 462delG | 18/F | Persistent fever, multiple lymphadenopathies and bilateral periorbital edema | Rituximab; APO; and cyclophosphamide + dexamethasone | Patient died of a hemorrhagic alveolitis, 12 days after starting chemotherapy |
| COMBINED IMMUNODEFICIENCIES WITH ASSOCIATED OR SYNDROMIC FEATURES | |||||||||
| Ataxia Telangiectasia* | (25) | 12 | NS | HL | NS | 10/8M, 4F | NR | NS | 10 pts died |
| 38 | NS | NHL | NS | 9/22M, 16F | NR | NS | 28 pts died | ||
| Ataxia Telangiectasia* | (26) | 1 | DNA repair defect | MZL | NS | 16/M | Chronic lymphadenitis, LN at left jaw, Cervical, celiac, para-aortic | Rituximab | CR |
| Ataxia Telangiectasia* | (27) | 1 | DNA repair defect | HL | NR | 14/M | Cervical, axillary and mediastinal LN | COPP | CR |
| Ataxia Telangiectasia* | (28) | 1 | EBV associated | NHL | ATM gene (exon 39 and c.6095G4A) | 13/M | Waldeyer's ring, intrapulmonary, abd., tonsillar, cervical LN | Rituximab, doxorubicin, dexamethasone, cytarabine, cyclophosphamide, etoposide, vincristine, HSCT | No recurrence on 3 y FU |
| Wiskott Aldrich* | (29) | 1 | EBV associated DNA repair defect | DLBCL | NR | 14/M | Cervical adenitis, neurological symptoms | Rituximab | Died |
| Wiskott Aldrich* | (30) | 1 | NS | BL | WASP gene missense mutation (105 C > T) in exon 1 | 12/M | Recurrent colicky abd. pain and bloody stools | Rituximab, CHOP | CR |
| Wiskott Aldrich* | (31) | 1 | EBV associated | DLBCL | NS | 15/M | Progressive respiratory distress, night sweats | Cyclophosphamide, prednisone, radiotherapy, laser surgery | Died of lung infection |
| Wiskott Aldrich* | (32) | 1 | EBV associated | HL | NS | 1 | Pulmonary hilar LN | ABVD | CR for more than 4 y |
| Wiskott Aldrich* | (33) | 1 | EBV associated | NHL | NR | 20/M | Lymphadenopathy, CNS, gastric wall, pulmonary lesions | Acyclovir, adenosine arabinoside | Died of sepsis |
| Wiskott Aldrich* | (34) | 1 | EBV associated | IL | NS | 13/M | Rectosigmoid tumor | Chemotherapy, excision, L-asparaginase therapy | Died of colon perforation |
| DiGeorge Syndrome* | (35) | 1 | EBV associated | INHL | NS | 10m/F | Hemiparesis due to cerebral mass, mediastinal LN | Untreated | Died |
| Cartilage hair dysplasia* | Unpublished | 1 | EBV associated | DLBCL | RMRP gene | 51/M | Incidental lung nodule | R-CHOP | CR |
| Cartilage hair dysplasia* | Unpublished | 1 | EBV associated | MZL | RMRP gene | 47/M | Fever, night sweats, lymphadenopathy | Rituximab | Under treatment with Rituximab for recurrence |
| Cartilage hair dysplasia | (36) | 10 | NS | Pt1: HL | 70A > G/70A > G | 20/M | NR | NR | Died in 1 m |
| Pt2: NHL | 70A > G/262G > T | 40/M | NR | NR | Died same m. | ||||
| Pt3: NHL | dupTACTCTGTGA at 13/70A > G | 45/F | NR | NR | Died in 3 m | ||||
| Pt4: NHL | 70A > G/70A > G | 46/F | NR | NR | Died in 6 m | ||||
| Pt5: NHL | Not tested | 22/F | NR | NR | Died in 2 m | ||||
| Pt6: NHL | 70A > G/70A > G | 6/F | NR | NR | Died in 9 m | ||||
| Pt7: NHL | Not tested | 21/M | NR | NR | Died in 1 m | ||||
| Pt8: NHL | Not tested | 26/M | NR | NR | Alive 4.5 y | ||||
| Pt9: NHL | 70A > G/70A > G | 32/M | NR | NR | Alive 11 y | ||||
| Pt10: NHL | 70A > G/70A > G | 33/F | NR | NR | Alive 4.5 y | ||||
| NBS | (37) | 8 | NS | Pt1: DLBCL | Homozygous 657del5 | 10/M | DLBCL at 10, 18, 23 and 26y | 1st event unknown, 2nd LMB-89, 3rd R-CHOP, 4th DHAP | Alive, CR at 27 y |
| Pt2: DLBCL | Homozygous 657del5 | 14/F | DLBCL at 14, 20y | 1st event unknown, 2nd LMB-89 without MTX | Died of liver failure after CYM protocol at 20 y | ||||
| Pt3: DLBCL | Homozygous 657del5 | 4/F | NR | LMB-89, without CTX, followed by individualized chemotherapy | Died of disease after second individual protocol at 5 y | ||||
| Pt4: DLBCL | Homozygous 657del5 | 6/F | NR | LMB-89, without CTX | Died of disease at 7 y | ||||
| Pt5: DLBCL | Homozygous 657del5 | 11/F | NR | LMB-89 without CTX, followed by individualized chemotherapy | Died of disease at 12 y | ||||
| Pt6: DLBCL | Homozygous 657del5 | 23/M | Switch from DLBCL to AILT at 26y | LMB-89; for AILT: BFM-90 followed by individualized chemotherapy | Died of disease after individual protocol at 27 y | ||||
| Pt7: BL | Homozygous 657del5 | 9/M | Burkit like lymphoma at 9, followed by DLBCL at 10 | 1st LMB-89, 2nd LMB-89 followed by individualized chemotherapy and splenectomy | Alive at 16 y | ||||
| Pt8: BL | Homozygous 657del5 | 5/F | NR | LMB-89 | PR, alive at 12 | ||||
| NBS | (38) | 11 | NS | Pt1: DLBCL | NR | 9/M | NR | NHL-BFM86 | CR 11 y after diagnosis |
| Pt2: DLBCL | NR | 15/F | B-NHL at 31 y, third malignancy Bi-linage leukemia at 34 y | NHL-BFM86 modified | Died at 34y from 3rd malignancy | ||||
| Pt3: BL | NR | 4/M | 2nd BL at 10 y | NHL-BFM90 | CR at 18y | ||||
| Pt4: IL | NR | 10/F | NR | NHL-BFM90 switched to CHOP because of progressive disease | Died 4.5 m after diagnosis | ||||
| Pt5: FL | NR | 7/F | 2nd DLBCL 13 m after diagnosis, third NHL (DLBCL) 8 y after diagnosis | NHL-BFM95 | Current under treatment (NHL-BFM modified) | ||||
| Pt6; BL | NR | 5/M | NR | NHL-BFM95 | CR 6 y after diagnosis | ||||
| Pt7: DLBCL | NR | 5/F | 2nd malignancy: ALCL-T 3.5 y after diagnosis | NHL-BFM95 modified | Death of lung infection 8 y after diagnosis | ||||
| Pt8: DLBCL | NR | 15/M | NR | NHL-BFM95 + Rituximab | CR 4 y after diagnosis | ||||
| Pt9: NHL | NR | 10/F | NR | NHL-BFM95 modified | Death of lung infection 1 m after end of treatment | ||||
| Pt10: DLBCL | NR | 9/F | 2nd malignancy: T-ALL 3.5 y after diagnosis | B-NHL BFM04 modified + Rituximab | Death during treatment, 8 m after diagnosis of T-ALL | ||||
| Pt11: ALCL | NR | 15/M | NR | NHL-BFM90 | CR 6 y after diagnosis | ||||
| Ataxia Telangiectasia | (38) | 11 | NS | Pt1: BL | NR | 16/M | NR | B-NHL-BFM04 modified | Chronic lung disease, death of pulmonal infection 1.9 y after diagnosis |
| Pt2: BL | NR | 7/M | NR | B-NHL BFM04 modified + Rituximab-Window | CR 2.7 y after diagnosis | ||||
| Pt3: DLBCL | NR | 6/M | NR | B-NHL BFM04 modified | CR 3.8 y after diagnosis | ||||
| Pt4: DLBCL | NR | 9/F | NR | NHL-BFM90 modified | Death of early relapse 1 y after diagnosis | ||||
| Pt5: DLBCL | NR | 5/M | 2nd malignancy: DLBCL 10 y after diagnosis | NHL-BFM95 modified | CR | ||||
| Pt6: DLBCL | NR | 11/M | 2nd malignancy: DLBCL 3 y after diagnosis | NHL-BFM95 modified | Death with pulmonary failure | ||||
| Pt7: DLBCL | NR | 7/F | NR | NHL BFM95 modified | CR 9.6 y after diagnosis | ||||
| Pt8: DLBCL | NR | 10/F | NR | NHL-BFM95 modified | Death of therapy toxicity 4 m after diagnosis | ||||
| Pt9: DLBCL | NR | 9/M | NR | NHL-BFM95 modified | CR 7.1 y after diagnosis | ||||
| Pt10: DLBCL | NR | 9/F | NR | NHL-BFM95 modified | CR 7 y after diagnosis | ||||
| Pt11: HL | NR | 12/M | NR | No chemotherapy | Death of progressive disease 1 m after diagnosis | ||||
| NBS | (39) | 10/26 | Defective antitumor immunosurveillance | Pt1: NHL | NR | 5/F | NR | NR | NR |
| Pt2: NHL | NR | 8/F | NR | NR | Death at 10 y | ||||
| Pt3: NHL | NR | 7/F | NR | NR | Death at 7 y | ||||
| Pt4: NHL | NR | 12/F | NR | NR | Death at 12 y | ||||
| Pt5: NHL | NR | 7/F | NR | NR | Death at 10 y | ||||
| Pt6: NHL | NR | 7/F | NR | NR | Death at 19 y | ||||
| Pt7: NHL | NR | 7/F | NR | NR | Death at 7 y | ||||
| Pt8: NHL | NR | 11/M | NR | NR | NR | ||||
| Pt9: NHL | NR | 29/F | NR | NR | Death at 29 y | ||||
| Pt10: HL | NR | 12/M | NR | NR | Death at 14 y | ||||
| NBS* | (40) | 11 | Two cases possibly EBV associated | Pt1: BL | NR | 9/M | Abdominal, splenomegaly (cervical tumor) | NR | Alive at 15 y |
| Pt2: DLBCL | NR | 24/M | Abdominal (inguinal LN) | NR | Died at 27 y | ||||
| Pt3: DLBCL | NR | 11/F | Generalized (axillary LN) | NR | Died at 12 y | ||||
| Pt4: DLBCL | NR | 6/F | Cervical LN | NR | Died at 7 y | ||||
| Pt5: DLBCL | NR | 4/F | Cervical LN | NR | Died at 6 y | ||||
| Pt6: DLBCL | NR | 15/F | Generalized (axillary LN) | NR | Died at 20 y | ||||
| Pt7: DLBCL | NR | 11/M | Cervical LN | NR | Alive at 27 y | ||||
| Pt8: DLBCL | NR | 4/M | Generalized cervical LN | NR | Died at 5 y | ||||
| Pt9: DLBCL | NR | 8/F | Generalized (axillary LN) | NR | Died at 10 y | ||||
| Pt10: HL | NR | 12/M | Cervical LN | NR | Died at 14 y | ||||
| Pt11: AILT-like | NR | 8/F | Generalized cervical LN | NR | Died at 8 y | ||||
| NBS | (41) | 4 | NS | Pt1: DLBCL | NR | 15/F | NHL-BFM | CR, LFU +6 y | |
| Pt2: ALCL (B) | NR | 6/F | NHL-BFM | Death of fungal sepsis after first course of therapy | |||||
| Pt3: DLBCL | NR | 9/M | NHL-BFM | CR, LFU +2.5 y | |||||
| Pt4: IL | NR | 10/F | NHL-BFM + RT | Initial nonresponse died after 5 m | |||||
| NBS | (42) | 1 | Defective DNA repair | DLBCL | Homozygous 657del5 | 17/M | Bilateral cervical LN, malaise, headache, epistaxis, symptoms of URI, fever, night sweats, and loss of weight, followed by the development of protruding tissue mass in the epigastrium | Modified CHOP + Rituximab | CR, 3 y in CR on LFU |
| NBS* | (43) | 1 | EBV associated | HL | Homozygous 657del5 | 5/F | Fever lasting for 2 m and mediastinal adenopathy | COPP/ABV | CR, 2 y in CR on LFU |
| NBS* | (44) | 12/57 | Chronic antigenic stimulation | NHL | NR | NR | NR | NR | 15 out of total 22 patients died, but 7 were clinically stable after early diagnosis and successful treatment |
| 2/57 | Chronic antigenic stimulation | HL | NR | NR | NR | NR | |||
| NBS | (45) | 30/149 | NS | NHL | NR | NR | NR | NR | 44% of all patients in CR, 54% dead due to disease progression |
| 7/149 | HL | NR | NR | NR | NR | ||||
| Dyskeratosis Congenita | (46) | 1 | Genetic insatiability | HL | NR | 30/M | NR | Radiation-chemotherapy | Died after 25 y (gastric adenocarcinoma) |
| Ataxia Telangiectasia | (3) | 1/10 | NS | 1 NHL | NR | NR | NR | NR | NR |
| Ataxia Telangiectasia | (41) | 2 | NS | Pt1: DLBCL | NR | 9/F | NHL-BFM | Relapse after 10 m, died after 1 y of diagnosis | |
| NS | Pt2: DLBCL | NR | 12/M | NHL-BFM | CR, LFU +1 y | ||||
| PNP deficiency | (41) | 1 | NS | ALCL (B) | NR | 2/F | dosages reduced | BMT (haploident.) in CR, BMT-related death | |
| Schimke Immuno-Osseous dysplasia | (47) | 1 | NR | NHL | SMARCAL1 missense mutation (R561H) | 8/M | Colicky abdominal pain and vomiting. Palpation of the abdomen revealed a hard mass in right upper abdomen. Intussusception secondary to NHL | Vincristine, cyclophosphamide, adriamycin and intrathecal methotrexate using half of their usual doses | Died due to septicemia following chemotherapy |
| Schimke Immuno-Osseous dysplasia | (48) | 3/71 | NS | NHL | SMARCAL mutation | NR | NR | NR | NR |
| Schimke Immuno-Osseous dysplasia* | (49) | 1 | EBV associated | BCL | Homozygous mutation of the SMARCAL1 gene (1146–1147delAA þ IVS6 þ 2delGT) | 5/M | Fever, mild cough | Chemotherapy | Died 1 m later due to multiorgan failure |
| CHARGE association with Hyper-IgM | (50) | 1 | Chronic antigenic stimulation | MZL | NR | 5/F | Suspected purulent bilateral conjunctivitis: Unresponsive On microscopy: salmon-colored, nodular lesions | Topical IFN-[alpha] 3 times a day 300,000 U/drop. | Resolved. No lesions at 1 y FU |
| PREDOMINANTLY ANTIBODY DEFICIENCIES | |||||||||
| Severe Ig deficiency | (41) | 1 | NS | DLBCL | NR | 14/F | VBL for palliation only | Died after 3 m | |
| IgG1, −3 and −4 deficiency | (41) | 1 | NS | BL | NR | 6/F | NHL-BFM | CR, LFU +5 y | |
| Selective IgA deficiency | (41) | 1 | NS | Burkitt-like | NR | 2/M | NHL-BFM | CR, LFU +0.5 y | |
| IgG-4 and IgM deficiency | (41) | 1 | NS | BL | NR | 5/F | B-NHL therapy per protocol full dosage | CR, LFU +4.5 y | |
| IgA, IgG2, and −4 deficiency | (41) | 1 | NS | BL | NR | 11/M | NHL-BFM | Reached CR, died of sepsis after second therapy course | |
| APDS | (51) | 2/8 | NS | Pt1: DLBCL | GOF mutation in the PIK3CD gene: E1021K (c.3061G > A) | 8/M | 2nd DLBCL at 19 y | Initially UKCCSG 9002 protocol, 2nd malignancy: CHOP + Rituximab | Died from large bowel perforation and bleeding 12 days after the third course of chemotherapy. |
| Pt2: HL | Heterozygous GOF mutation in the PIK3CD gene: E1021K | 11/M | Cervical LN enlargement | Chemotherapy and RT | CR, alive FU of more than 10 y | ||||
| APDS | (52) | 6/53 | NS | 2 DLBCL, 1 HL, 1 NMZL,1 Hodgkin-like | E1021K mutation | 1.5–27/NR | NR | NR | 3 died |
| APDS | (53) | 1/17 | NS | MZL | E1021K mutation | NR | NR | NR | NR |
| Selective IgA deficiency | (54) | 1/386 | NS | NHL | NR | 38/M | NR | NR | NR |
| CVID | (55) | 1 | NS | DHL | NR | 47/M | Abd pain, numbness, and weakness in legs. | RT, cyclophosphamide, vincristine, procarbazine, prednisone | FU 3.5 y: CR |
| CVID | (56) | 1 | NS | EZMZL | 16/F | Cough, wheezing | Prednisolone | Alive | |
| CVID | (57) | 1 | NS | EZMZL | 44/F | Chlorambucil and prednisone | Recurrence after 6m | ||
| CVID | (58) | 54 | EBV possibly | BCL | NR | NR | NR | NR | NR |
| CVID* | (59) | 3/220 | EBV associated | BCL | NR | NR | NR | NR | NR |
| CVID | (60) | 7 | NS | BCL | NR | 46**/F | NR | NR | NR |
| 9 | NS | BCL | NR | 42**/M | NR | NR | NR | ||
| CVID* | (61) | 1 | EBV or ITK mutation | HL | NR | 25/F | NR | Rituximab and brentuximab vedotin. | CR |
| CVID | (62) | 3 | NS | Pt1: BCL | NR | 2/M | Generalized LN | NR | Died at 23y |
| Pt2: BCL | NR | 61/F | NR | NR | NR | ||||
| Pt3: BCL | NR | 66/F | NR | NR | NR | ||||
| CVID | (63) | 22/248 | NS | Pt1: NHL | NR | 13/F | NR | Chemotherapy (CHOP) | Died, age 13 |
| Pt2: NHL | NR | 31/F | NR | Surgery | Alive 1 y later | ||||
| Pt3: NHL | NR | 41/M | NR | Chemotherapy, HSCT | Died, age 41 | ||||
| Pt4: NHL | NR | 44/F | NR | Surgery | Unknown, alive 8 y later | ||||
| Pt5: NHL | NR | 45/M | NR | None | Alive, 1 y later | ||||
| Pt6: NHL | NR | 46/F | NR | Chemotherapy (Type?) | Died | ||||
| Pt7: NHL | NR | 48/M | NR | None | Died, age 48 | ||||
| Pt8: NHL | NR | 52/F | NR | Chemotherapy (CHOP) | Died, age 56 | ||||
| Pt9: NHL | NR | 52/F | NR | Radiation | Alive, 2 y later | ||||
| Pt10: NHL | NR | 54/F | NR | Surgery, surgery, chemotherapy | Alive at age 68 | ||||
| Pt11: NHL | NR | 54/F | NR | Surgery | Died other causes, 15 y later, age 69 | ||||
| Pt12: NHL | NR | 56/F | NR | M-BACOD, CHOP, RT, CP | Alive, 12 y later | ||||
| Pt13: NHL | NR | 63/M | NR | CHOP, M-BACOD, M2 | Died, age 65 | ||||
| Pt14: NHL | NR | 67/F | NR | Chemotherapy (C-MOPP) | Died, age 68 | ||||
| Pt15: NHL | NR | 67/F | NR | Chemotherapy (CHOP) | Alive, stable 8 y later | ||||
| Pt16: NHL | NR | 71/F | NR | Chemotherapy (C-MOPP) | Died, age 72 | ||||
| Pt17: NHL | NR | 72/F | NR | Alpha interferon | Died, age 73 | ||||
| Pt18: NHL | NR | 75/F | NR | Radiation | Alive, stable, 2 y later | ||||
| Pt19: NHL | NR | 77/M | NR | Chemotherapy (Type?) | Died, age 77 | ||||
| Pt20, Pt 21, Pt 22: HL | NR | 8/M Rest NR | NR | Splenectomy and chemotherapy in Pt20 | Pt20 relapsed after 12 years | ||||
| CVID | (64) | 5/5 | NS | Pt1: EZMZL | NR | 56/F | Parotid, 2nd Breast, 3rd DLBCL in sternum after 11 y | Radiation, excision, CHOP, rituximab | Recurrence |
| Pt2: EZMZL | NR | 35/F | Lung | None | Well | ||||
| Pt3: EZMZL | NR | 31/F | Parotid | Excision, radiation | Recurrence | ||||
| Pt4: EZMZL | NR | 42/M | Lung involvement | CVP and Rituximab 2, CHOP | Recurrence | ||||
| Pt5: EZMZL | NR | 35/F | Lung | R-CHOP | CR | ||||
| CVID | (65, 66) | 9/117 | Unknown | Pt1: DLBCL | NR | 12/F | Liver, Spleen | CHOP | Died at 13 y |
| Pt2: DMSL | NR | 54/F | Right Inguinal Node | CHOP | Died at 69 due to other causes | ||||
| Pt3: DMSL | NR | 50/F | Pelvis, | CHOP | Died at 56 y | ||||
| Pt4: DLBCL | NR | 48/F | Proximal jejunum | Surgery | Alive, 8 y later | ||||
| Pt5: Follicular | NR | 54/F | Parotid, 1 y later FL in axilla | Surgery for both | Alive, after 3 y | ||||
| Pt6: diffuse small cleaved cell | NR | 56/F | Pelvic nodes | M-BACOD, CHOP, RT, CP | Alive | ||||
| Pt7: DLBCL | NR | 57/F | Supraclavicular area, abdomen | C-MOPP | Died at age 68 | ||||
| Pt8: DLBCL | NR | 65/F | Lymph nodes, lungs | C-MOPP | Died at age 72 | ||||
| Pt9: DLBCL | NR | 70/F | Cervical lymph nodes | Alpha-Interferon | Alive | ||||
| CVID | (54) | 5/176 | NS | Pt1: NHL | NR | 52/F | NR | NR | NR |
| Pt2: NHL | NR | 59/F | NR | NR | NR | ||||
| Pt3: NHL | NR | 76/F | NR | NR | NR | ||||
| Pt4: HL | NR | 49/F | NR | NR | NR | ||||
| CVID | (67) | 1 | Defective antitumor immunosurveillance | DHL | NR | 44/F | Abd. pain, slight diarrhea, weight loss. Palpable mass in right abdomen | Resection and irradiation | 4-y F/U: CR |
| CVID | (68) | 1 | Chronic antigenic stimulation | IL | NR | 75/W | Weight loss, numbness and tingling in extremities | Surgical resection | Death post-op due to septicemia |
| CVID | (69) | 1 | Defective antitumor immunosurveillance | MZL | NR | 39/M | Periumbilical pain, severe diarrhea, weight loss | NR | NR |
| CVID | (70) | 4/224 | NS | NHL | NR | NR | NR | Chemotherapy + Rituximab + transplant | NR |
| CVID | (71) | 5/247 | NS | Jejunal, 1 histiocytic, 1 HL, 2 BCL | NR | NR | NR | NR | 4 died, HL responded to RT |
| CVID* | (72) | 1 | NS | EMZL | NR | 41/F | Malaise, dyspnea and productive cough | IVIG, chlorambucil and prednisone | |
| CVID | (73) | 10/334 | NS | NHL | NR | NR | NR | NR | 5 died. |
| CVID | (3) | 10/416 | NS | 1 DLBCL, 2 FL,1 BL, 1 SLL,1 EMZL, 3 NHL,1 WM | NR | NR | NR | NR | NR |
| CVID | (74) | 23 | NR | NHL | NR | NR/28F, 11M | NR | 11 died of lymphoma, 12 alive | |
| 3 | NR | DLBCL | NR | 2 died of lymphoma, 1 also had severe lung disease, 1 alive | |||||
| 4 | NR | HL | NR | 2 died of lymphoma, 2 alive | |||||
| 5 | NR | EMZL | NR | 3 no treatment, 2 chemotherapy | All alive | ||||
| 1 | NR | MZL | NR | No treatment given, alive | |||||
| 1 | NR | Diffuse poorly differentiated | NR | Died of lymphoma | |||||
| 1 | EBV associated | T -cell rich BCL | NR | Died of lymphoma | |||||
| Selective IgA deficiency | (75) | 1 | Chronic antigenic stimulation | PCMZL, MZL | MZL: monoclonal amplification of 98 base pairs in FR3A region of the IGH gene | 43/F | Asymptomatic subcutaneous nodules in upper extremity. Enlarged axillary, mediastinal LN | RituximabRadiotherapy and local excision | CR followed by repetitive relapses |
| DISEASES OF IMMUNE DYSREGULATION | |||||||||
| ALPS* | (76) | 1 | EBV associated | FL, DLBCL, HL | c.784A>T mutation in TNFRSF6, | 33/M | Lymphadenopathy | R-CHOP | CR |
| XLP1 | (77) | 3 | Defective antitumor immunosurveillance | Pt1: BL | SH2D1A p.E17D c.51 G > C | 6/M | Acute abd. obstruction on presentation, night sweats, weight loss. | NHL-BFM95, full dosage, + Rituximab | CR |
| Pt2: DLBCL | SH2D1A p.W64C c.192G > T | 14/M | Painless mass of about 2.0 × 2.5 cm in size on the front right-side chest wall | B-NHL-M2004, full dosage + Rituximab | Died at the age of 19 | ||||
| Pt3: DLBCL | SH2D1A c.53insA > T | 6/M | Testicular DLBCL | NHL-BFM90 + Rituximab | Died at 8.3 y | ||||
| XLP1* | (78) | 1 | NS | BL | exon 2 of the SH2D1A gene at position 146 (c146insG | 4/M | Lymphadenopathy, HS, cerebellar tumor | ETO, DXM, cyclophosphamide | PR died of ICH |
| XLP* | (79) | 2 | EBV associated | Pt1: BL | NR | 1.6/M | Palpable abd. mass Malaise, poor appetite, failure to thrive. | Protocol LMB-84 | Died of hemorrhage 6 m after stopping therapy. |
| Pt2: BL | t(8;14) (q24;q32) | 2/M | Abd. Mass, malaise and failure to thrive. | Protocol LMB-84 | Relapse after 17 m. Died. | ||||
| ITK deficiency* | (80) | 1 | EBV associated | HL | 48, X,X,+2,der(10)add(10)(p13) add(10)(q34),del(11)(q22q23), + 12,-13, + 1B2mar | 5/F | Cervical and inguinal lymphadenopathy | IFS, vinorelbine, etoposide, cytarabine, gemcitabine) RT, HSCT | CR |
| ITK deficiency* | (81) | 2 | EBV associated | Pt1: NHL | NS | 6/F | Cervical and occipital Lymphadenopathy | CHOP and anti CD20 Ab | Died of infection |
| P2: HL | NS | 2.5/M | NR | Chemotherapy | NR | ||||
| ITK deficiency* | (82) | 1 | EBV associated | HL | NS | Lung and Kidney | HSCT, Rituximab, Fludarabine, Melphalan, ATG | CR | |
| ITK deficiency* | (83) | 4 | EBV associated | Pt1: HL | IKT gene: 1764C>G: YS886 | 4/F | LN | NR | Died at age 6 |
| Pt2: HL | IKT gene: 1764C>G: YS886 | 5/M | LN | Induction Therapy | PreHSCT, age 10 | ||||
| Pt3: HL | IKT gene: 1764C>G: YS886 | 3/M | LN | HSCT | Alive | ||||
| Pt4: DLBCL | IKT gene: 1497delT: D500T, F501L, MS03X | 6/F | Lungs | HSCT | Died from GVHD in 6 m | ||||
| ITK deficiency* | (84) | 3 | EBV associated | Pt1: HL | ITK gene: single homozygous mutation c. 1764 C->G which causes a premature stop-codon Y588X | 5/F | Lymphadenopathy and Hepatosplenomegaly | Rituximab, VP-16, vinorelbine, GMC | Died of respiratory failure |
| Pt2: HL | 5/M | Lymphadenopathy | Chemotherapy | CR | |||||
| Pt3: HL | 3/M | Lymphadenopathy and HS | HSCT with fludarabine, melphalan, ATG, rituximab | Alive | |||||
| ITK deficiency* | (85) | 2 | EBV associated | Pt1: HL | Homozygous mutation in ITK on ch 5q31–5q32. | 6/F | Generalized LN, HS, nasal, concha tumor | Prednisone, procarbazine, vincristine, cyclophosphamide, ADM + rituximab | Died of respiratory failure at 10 |
| Pt2: HL | homozygous mutation in ITK 5q31–5q32. | 1/F | Retroperitoneal and abd. LN, HS | GNC, steroid, rituximab, HSCT | Died of ischemic brain injury | ||||
| CD70 deficiency* | (86) | 1 | EBV associated | HL | 3/M | Recurrent fever, lymphadenopathy, HS | Initially chemotherapy and radiotherapy Rituximab at 4 HSCT at 10 | CR after chemo/radiotherapy No relapse of HL, however recurrent lymphoproliferative episodes. Well since HSCT. | |
| CD70 deficiency* | (87) | 3 | EBV associated | Pt1: HL | Homozygous c.250delT resulting in p.S84Pfs27X | 17/M | Peptic ulcer, gastritis, splenomegaly and lymphadenopathy | doxorubicin, bleomycin, vinblastine, and dacarbazine | CR, F/U at 29 y: Stable |
| Pt2: HL | Homozygous c.555_557delCTT resulting in p.F186del | 2/M | Diffuse cervical lymphadenopathy | Initially OPPA and COPP ABVD + radiotherapy after relapse | CR after ABVD/radiotherapy F/U at 16: CR | ||||
| Pt3: HL | Homozygous c.555_557delCTT resulting in p.F186del | 3/M | Chronic cervical lymphadenopathy | ABVD gemcitabine, vinorelbine, and brentuximab were followed by auto-HSCT | Relapse after ABVD, CR after HSCT | ||||
| CD27 deficiency* | (88) | 5 | EBV associated | Pt1: DLBCL | Homozygous c.G158A, p.C53Y | 2/F | NR | None | Died at 2 y |
| Pt2: DLBCL | Homozygous c.G158A, p.C53Y | 22/F | NR | CHOP | Died at 22 | ||||
| Pt3: HL | Compound c.G24A, p.W8X; c.C319T p.R107C | 15/F | Persistent cervical lymphadenopathy | EuroNet-PHL-C1 | Alive | ||||
| Pt4: HL | Homozygous c.G287A, p.C96Y | ?/F | NR | None | Died at 20 y | ||||
| Pt5: HL | Homozygous c.G287A, p.C96Y | 8/M | NR | ABVD, radiotherapy | CR | ||||
| XMEN* (MAGT1 deficiency) | (89, 90) | 2 | EBV associated | 1. BL | g.43183delC | 7/M | 2nd malignancy at 14 | NR | Alive at 16 y |
| 2. HL | g.46604G>T | 17/NR | 2nd malignancy at 22 | HSCT | Died at 23 y of HSCT complications | ||||
| XMEN | (91) | 1 | EBV associated (suspected) | DLBCL | c.712C > T, p.R238X | 57/M | Lymphadenopathy, HS and B-symptoms | RCHOP, RGCVP | Died at 58 y from DLBCL |
| XMEN* | (92) | 1 | EBV associated | HL | c.555dup, p. Tyr186Ilefs*2 | 15/M | Influenza-like symptoms | COPP and ABVD | Alive at 17 y |
| CTPS1 deficiency* | (93) | 2 | EBV associated | Pt1: NHL | NR | 6/F | NR | Died at 6 y | |
| Pt2: NHL | NR | 1/M | NR | HSCT | Alive at 2 y | ||||
| Hypergammaglobulinemia | (41) | 1 | NS | DLBCL | NR | 1/F | No therapy received | Died of disease progression after 6 m | |
| IL-10R deficiency | (94) | 5 | Defective antitumor immunosurveillance | Pt1: DLBCL | IL-10RB gene: homozygous missense in exon 2 (p.Y59C) | 5/M | NR | COP, COPADM 3 2, CYM 3 2 | Died of disease progression |
| Pt2: DLBCL | IL-10RB gene: heterozygous composite frameshift mutation in exon 7 (F269fsX275) + missense mutation in exon 5 (p.W204C) | 5/M | NR | COP, R-COPADM | Died during treatment | ||||
| Pt3: DLBCL | homozygous nonsense in exon 3 of IL-10RB (p. E141X) | 6/M | NR | COP, R-COPADM, R-CYM, HSCT | Remission, alive (+12 m) | ||||
| Pt4: DLBCL | homozygous del (g.11930-17413 del) in IL-10RB. | 5/M | NR | COP, COPADM, R-CYM, R-ICE | Remission, alive (+18 m) | ||||
| Pt5: DLBCL | Homozygous c.368-10 C.G in intron 3 of IL-10RA. | 6/M | NR | Up-front R prephase | Remission, alive | ||||
| DEFECTS IN INTRINSIC AND INNATE IMMUNITY | |||||||||
| Whim Syndrome* | (95) | 1 | EBV associated | BCL | NR | 30/M | Red dermal facial nodules Axillary mass Axillary, hilar, Inguinal LN | 6 cycles CHOP + G-CSF before each cycle | Resolved after 6 cycles. |
| Whim Syndrome* | (96) | 1 | EBV associated | BCL | NR | 26/F | Fatal EBV+ B cell Lymphoma in the intestine and other organs. | CHOP | No response. Died of perforation and hemorrhage |
Abd, (abdominal); ABVD, (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine); AILT, (angioimmunoblastic T cell lymphoma); APO, (doxorubicin, vincristine, 6-MP, and prednisone); APDS, (activated phosphoinositide 3-kinase d syndrome); BCL, (B cell lymphoma); BL, (Burkitt lymphoma); ALPS, (Autoimmune lymphoproliferative syndrome); COP, (cyclophosphamide, vincristine, prednisone); COPADM, (cyclophosphamide, vincristine, prednisone, doxorubicin, methotrexate); CHOP, (cyclophosphamide, adriamycin, vincristine, prednisolone); COPP, (Cyclophosphamide, Oncovin, Procarbazine, Prednisone); CP, (cis-platinum); C-MOPP, (cyclophosphamide, oncovin, procarbazine, prednisone); CYM, (cytarabine, methotrexate); DHL, (diffuse histiocytic lymphoma); EMZL, (extra nodal marginal zone lymphoma); F, (female); G-CSF, (Granulocyte colony-stimulating factor); HLH, (hemophagocytic lymphohistiocytosis); ICE, (ifosfamide, carboplatin, etoposide); IL, (immunoblastic lymphoma); INHL, (immunoblastic NHL); LFU, (last follow up); LN, (lymph node); LPD, (lymphoproliferative Disease); M, (male); m, (months); M-BACOD, (methotrexate, doxorubicin, cyclophosphamide, vincristine, dexamethasone); ML, (Malignant Lymphoma); M2, (vincristine, cyclophosphamide); NHL-BFM, (Non-Hodgkin Lymphoma-Berlin-Frankfurt-Münster); NHL, (Non-Hodgkin Lymphoma); NMZL, (nodal marginal zone lymphoma); LL, (lymphoplasmacytic lymphoma); n, (number of patients); OPPA, (Oncovin, procarbazine, prednisone, and doxorubicin); PDC, (plasmacytoid dendritic cells); pt, (patient); PCMZL, (primary cutaneous marginal zone lymphoma); PE, (Physical Examination); PTCL, (peripheral T cell lymphoma); RT, (radiation therapy); R, (Rituximab); WM, waldenstrom macroglobulinemia; XLP1, (X-linked lymphoproliferative disease type I); y, (years).
*
EBV positive,
**
median age.