Iatrogenic Immunodeficiency Associated Lymphoproliferative Disorder in Patients with Acute Lymphoblastic Leukemia:A Case Series

Abstract

Iatrogenic immunodeficiency associated lymphoproliferative disorders (LPDs) with a primary diagnosis of acute lymphoblastic leukemia (ALL) seen is an extremely rare entity with no formal WHO classification with only 2 other cases reported in literature. We describe 3 patients aged 15–25 years developing LPDs after being on maintenance chemotherapy which regressed on withdrawal of immunosuppression and are currently on follow up (Table 1). Patient 1 presented with progressive neck swelling for 2 months. Neck node biopsy showed EBV related B-cell lymphoproliferation. In 6 months, there was a recurrence of symptoms. PET-CT scan revealed bilateral cervical nodes. Lymph node biopsy was suggestive of Hodgkin’s Lymphoma. His maintenance therapy (6-MP and methotrexate) was discontinued after which he reported regression of nodes and is now on follow-up with no evidence of recurrence after 20 months. Patient 2 presented with high grade fever and dry cough for 2 months along with dyspnea and loss of appetite. Biopsy showed inflamed mucosa with histiocytes, lymphocytes along with large scattered atypical cells. Immunochemistry was indicative of EBV associated lymphoid proliferation. PET CT scan showed metabolic activity along the nasopharynx. Her maintenance was restarted with no recurrence of symptoms. Patient is asymptomatic after completing 2 years of maintenance therapy. Patient 3, a year later, while on maintenance presented with cervical lymphadenopathy. USG revealed left cervical enlarged nodes. The biopsy showed high grade hematolymphoid proliferation made of large cells with necrosis. Immunochemistry was suggestive of EBV associated lymphoid proliferation. A PET CT scan showed metabolic activity in right tonsil and left cervical lymph nodes. Peripheral blood PCR for EBV DNA revealed\\ 100 copies/ml. Patient was restarted on maintenance therapy with a 50% dose reduction after discontinuing for 3 weeks. He completed 2 years of maintenance and is on follow-up. The current classification does not include separate category for cancer chemotherapy related lymphoproliferative disorders. Nor are these LPDs classified as per histopathology thus lacking precision. There is a need to develop a separate classification as it may prompt research to understand pathogenesis and design therapies to overcome them [1] [2]. There are a total of 71 cases reported in the literature of individuals developing LPDs after appropriate cancer therapy of which only 2 who had a primary diagnosis of acute lymphoblastic leukemia like our patients [1]. On the & Hasmukh Jain [email protected]