Hematological malignancies (HM) developed on underlying primary immunodeficiencies (PID) are rare and of unusual features. Differentiating between malignant and non-malignant lymphoproliferation in cases of pediatric hematology and oncology and revealing their molecular predisposition demonstrate the complex interplay between PID and HM. We retrospectively studied a case series of seven pediatric patients, all with PID with manifestations raising suspicion for HM or hypereosinophilic syndrome (HES) or confirmed HM of lymphoid origin. Combined immunodeficiency (CID) without detection of a known mutated gene or with ataxia-telangiectasia (AT), STAT3 gain of function (GOF), DOCK8 deficiency, and CTLA4 deficiency were diagnosed in three, one, one, one, and one patient, respectively. Acute lymphoblastic leukemia and Hodgkin lymphoma followed by second primary Burkitt lymphoma were diagnosed in one patient with CID each, while lymphomatoid granulomatosis in one patient with AT. Lymphoproliferative disease occurred in STAT3 GOF, CTLA4 deficiency and CID, one patient each, and idiopathic HES in DOCK8 deficiency (median age at presentation of PID or any hematological manifestation: four years). Four patients underwent hematopoietic cell transplantation (HCT) for STAT3 GOF, DOCK8 deficiency and CID in one, one, and two cases, respectively (median age: 10 years). At the last follow-up, all transplanted patients were alive. Reporting on patients’ phenotype, genotype and course of disease shed light on the prevalence, characteristics, and pathophysiology of HM complicating PID. Discriminating the non-yet malignant lymphoproliferation from its malignant equivalent on the same pathophysiology background proved of additional value. Outcomes of PID after HCT, herein reported, are favorable.

在潜在的原发性免疫缺陷 (PID) 上发展的血液系统恶性肿瘤 (HM) 是罕见的且具有不寻常的特征。在儿科血液学和肿瘤学病例中区分恶性和非恶性淋巴增殖并揭示它们的分子易感性证明了 PID 和 HM 之间复杂的相互作用。我们回顾性研究了 7 名儿科患者的病例系列，所有患者均患有 PID，其表现引起怀疑 HM 或嗜酸性粒细胞增多综合征 (HES) 或证实为淋巴源性 HM。在未检测到已知突变基因或共济失调毛细血管扩张症 (AT)、STAT3 功能获得 (GOF)、DOCK8 缺陷和 CTLA4 缺陷的情况下，在 3 名、1 名、1 名、1 名和 1 名患者中诊断出联合免疫缺陷 (CID)，分别。急性淋巴细胞白血病和霍奇金淋巴瘤，其次是第二原发性伯基特淋巴瘤，各有一名 CID 患者被诊断出，而一名 AT 患者被诊断为淋巴瘤样肉芽肿。淋巴增生性疾病发生在 STAT3 GOF、CTLA4 缺乏症和 CID 中，各 1 名患者，以及 DOCK8 缺乏症中的特发性 HES（出现 PID 或任何血液学表现的中位年龄：4 岁）。4 名患者分别接受了 1 例、1 例和 2 例 STAT3 GOF、DOCK8 缺陷和 CID 的造血细胞移植（HCT）（中位年龄：10 岁）。末次随访时，所有移植患者均存活。对患者表型、基因型和病程的报告揭示了 HM 并发 PID 的患病率、特征和病理生理学。在相同的病理生理学背景下，将非恶性淋巴增殖与其恶性等效物区分开来证明了额外的价值。本文报道的 HCT 后 PID 的结果是有利的。