Lymphoma Secondary to Congenital and Acquired Immunodeficiency Syndromes at a Turkish Pediatric Oncology Center

Abstract

The prevalence of lymphoma in primary immunodeficiency cases and autoimmune diseases, as well as on a background of immunodeficiency following organ transplants, is increasing. The lymphoma treatment success rate is known to be a low prognosis. Our study aimed to emphasize the low survival rates in immunodeficient vs. immunocompetent lymphoma patients and also to investigate the effect of rituximab in patients with ataxia telangiectasia and other immunodeficiencies. We summarized the clinical characteristics and treatment results of 17 cases with primary immunodeficiency that developed non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) retrospectively. Seven patients were diagnosed with ataxia-telangiectasia, two with common variable immunodeficiency, two with selective IgA deficiency, one with X-related lymphoproliferative syndrome, one with Wiskott-Aldrich syndrome, one with Epstein-Barr virus-related lymphoproliferative syndrome, one with interleukin-2-inducible T-cell kinase (ITK) deficiency, and one with lymphoma developing after autoimmune lymphoproliferative syndrome (ALPS). One patient underwent a renal transplant. Of the nine males and eight females (aged 3-12 years, median = 7) that developed lymphoma, seven were diagnosed with HL and ten with NHL (seven B-cell, three T-cell). The NHL patients were started on the Berlin-Frankfurt-Münster, POG9317, LMB-96, or R-CHOP treatment protocols with reduced chemotherapy dosages. HL cases were started on the doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and/or cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) protocol, also with modified dosages. Importantly, all seven cases of HL are alive and in remission, while six of the ten NHL patients have died. Primary immunodeficiency is a strong predisposing factor for developing lymphoma. Low treatment success rates relative to other lymphomas and difficulties encountered during treatment indicate that new treatment agents are needed. While some success has been achieved by combining rituximab with lymphoma treatment protocols in B-NHL cases with primary immunodeficiency, the need for new treatment approaches for these patients remains critical.

Primary pulmonary lymphoma in children

“…NHL is a predominant malignancy in a number of primary immunodeficiency diseases. The incidence of NHL in immunodeficient patients was 59%, and the incidence of immunodeficiency was 17.5% in NHL [8–10]. Although the mechnisms of the increased incidence of lymphoproliferative disease in immunodeficient patients are not fully understood, deterioration in immunoregulation, chronic antigenic stimulation, and tumor suppressor system dysregulation are thought to be the main explanation for it [7, 11, 12].…”

Primary Immunodeficiency and Cancer in Children; A Review of the Literature

“…Rituximab was administered to patients with DLBCL or Burkitt lymphoma (BL) with an AT or renal transplant background as a first-line treatment, and also in the relapse protocol for the BL cases with an EBV-associated lymphoproliferative disease background and the B-cell lymphoblastic lymphoma cases with an AT background. Rituximab was not found to increase survival compared to other treatment modalities without rituximab [12]. In patients with lymphomas that expressed CD20, reduced-dose chemotherapy with rituximab as the first-line treatment showed a beneficial effect [12].…”

“…Since lymphoma is the leading cancer type among patients with PID, there are studies focusing especially on it. Tanyıldız et al, assessed 100 childhood lymphoma cases (57 NHL, 43 HL) [12]. They compared the survival rates among immunodeficient and immunocompetent patients and they also sought the efficacy of rituximab in patients with PID.…”

“…Seventeen (17%) of these patients with PID developed lymphoma (NHL in 10 of 17) and the median age was 6 years (3-16) at diagnosis with an increased female/ male ratio. The diagnoses included AT (n=7), CVID (n=2), selective IgA deficiency (n=2), autoimmune lymphoproliferative syndrome (ALPS;n=1), WAS (n=1), interleukin-2-inducible Tcell kinase (ITK) deficiency (n=1), X-linked lymphoproliferative syndrome (XLPS; n=1), and Epstein-Barr virus (EBV)-associated lymphoproliferative syndrome (n=1) [12]. Rituximab was administered to patients with DLBCL or Burkitt lymphoma (BL) with an AT or renal transplant background as a first-line treatment, and also in the relapse protocol for the BL cases with an EBV-associated lymphoproliferative disease background and the B-cell lymphoblastic lymphoma cases with an AT background.…”

“…Rituximab was not found to increase survival compared to other treatment modalities without rituximab [12]. In patients with lymphomas that expressed CD20, reduced-dose chemotherapy with rituximab as the first-line treatment showed a beneficial effect [12]. Seidemann et al, reported 19 patients with PID who developed NHL within a total of 1413 cases [13].…”