Polycythaemia following treatment of lymphoplasmacytic lymphoma

Background

Anaemia is common in patients with lymphoplasmacytic lymphoma (LPL) at presentation.1 This is usually due to marrow infiltration by malignant cells. It recovers to various degrees during treatment and follow-up. Polycythaemia during treatment of LPL is a very rare phenomenon. There are case reports of simultaneous occurrence of Waldenström macroglobulinaemia and polycythaemia vera (PV),2 chronic lymphocytic leukaemia (CLL) and PV,3 and follicular lymphoma and PV.4 Other lymphoproliferative disorders have also been reported to have PV concomitantly or during patient’s follow-up post-treatment. A case report of polycythaemia occurring after treatment of Hodgkin lymphoma,5 and acute undifferentiated leukaemia also exist.6 LPL has not been reported to present with polycythaemia during follow-up. We are reporting the first case of polycythaemia of undetermined aetiology following treatment of a case of LPL.

Case presentation

A 61-year-old man presented to the department of clinical haematology with history of severe generalised weakness, fatigue and multiple swelling in cervical, axillary and inguinal region for a period of past 2 years. There was no history of fever, bleeding, bone pain, headache or visual impairment. The patient had a history of 7 units of packed red blood cell (PRBC) transfusion at local hospitals in the last 3 months. He was not having any comorbidities like diabetes, hypertension, coronary heart disease or chronic pulmonary disease. He was a non-smoker and was not taking any medications other than iron and multivitamins. There was no significant response to current medications. On examination, the patient had severe pallor, generalised lymphadenopathy with the largest node measuring 3×2 cm in the inguinal region, hepatomegaly 04 cm below costal margin but no splenomegaly. Rest of the general examination and systemic examination findings were unremarkable.

Baseline laboratory investigations showed haemoglobin (Hb) 31 g/L, total leucocyte count 5.2×10⁹/L and platelet count of 240×10⁹/L. Peripheral smear showed lymphocytic predominance with presence of 10% lymphoplasmacytoid cells. Liver and renal function tests were within normal limits, and he was negative for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody and human immunodeficiency virus (HIV) antibody by ELISA.

Bone marrow aspiration and biopsy revealed non-Hodgkin’s lymphoma with marrow infiltration. On immunohistochemistry (IHC) tumour cells were positive for CD20 and CD138 while negative for Tdt and CD3. Serum protein electrophoresis was performed and showed a distinct M band (1.61 g/dL) in the gamma region. Immunofixation electrophoresis revealed IgG +k and diagnosis of LPL was made. His treatment plan was to give combination chemotherapy of VI cycle of bortezomib/rituximab/dexamethasone (BRD) regimen and then 3 monthly maintenance with rituximab for 2 years.

After receiving 03 cycles of BRD chemotherapy, Hb improved to 114 g/L, and the patient became clinically asymptomatic. After 06 cycles of BRD chemotherapy Hb improved to 140 g/L and bone marrow examination showed complete remission. The first dose of 3 monthly maintenance rituximab was given on 5 April 2017 with a Hb value of 172. During maintenance phase Hb value remained >165 gm/L and reached up to a maximum value of 201 g/L after third dose of maintenance rituximab and 189 g/L after completing the maintenance phase. He was not taking any anabolic steroid, over the counter drugs or any complementary medicine drug at that time. During the last 3 years, his Hb has persistently been above 165 g/L. Figure 1 shows the Hb pattern of this patient at diagnosis, during treatment, during maintenance and during follow-up.

Figure 1

Showing haemoglobin trend in this patient at baseline, during treatment, during maintenance and during follow-up. His total leucocyte count and platelet count was consistently normal during this period. R, rituximab.

Investigations

Considering it as a case of polycythaemia, we investigated this patient on similar lines to know the underlying cause. His chest X-ray, Ultrasonography of abdomen, 2 dimentional echocardiography (2D-ECHO) and O₂ saturation at rest and after exercise was normal. His serum erythropoietin(s EPO) value was 5.7 mIU/mL which was low normal (normal range 4.3–29 mIU/mL). These investigations ruled out the possibility of secondary polycythaemia reliably. Bone marrow findings were not consistent with the morphological findings of PV and also did not show any evidence of disease progression/recurrence. Mutations analysis of Janus kinase- 2 (JAK-2) V617F and exon 12 by PCR were negative.

Treatment

The patient continued to receive three monthly maintenance rituximab, and the last dose was given on 12 December 2018. He was started on regular Ecosprin 75 mg/day. He did not receive any specific treatment for polycythaemia as he was asymptomatic most of the times. Phlebotomy was done infrequently, especially in situations when his Hb was >20 g/dL or he had some symptoms like headache or giddiness.

Outcome and follow-up

The patient is being followed up every 2 months in haematology out patient department. He has completed 2 years of follow-up postmaintenance rituximab and doing fine without any disease progression or deterioration. The patient has not developed any vascular event and has no signs of hyperviscosity at present.