Indian Journal of Cancer Medknow Publications on behalf of Indian Cancer Society ISSN: 0019-509X EISSN: 1998-4774 Vol. 40, Num. 3, 2003, pp. 116-117

Indian Journal of Cancer, Vol. 40, No. 3, (July - September 2003) , pp. 116-117

Case Report

Primary Plasma Cell Leukemia Occuring in the Young

Raj RS, Najeeb S, Aruna R, Pavithran K,* Thomas M

Medical College Hospital, Thiruvananthapuram - 695011, India; and *Department of Medical Oncology, Rajiv Gandhi Cancer Institute & Research Centre, Rohini, Sector-5, New Delhi -110085, India.
Correspondence to: K. Pavithran. E-mail: drkpavithran@hotmail.com

Code Number: cn03019

ABSTRACT: Plasma Cell Leukemia (PCL) is a rare form of plasma cell dyscrasia. Plasma cell leukemia has two variants: the primary form presents de novo in patients with no previous history of multiple myeloma (MM); the secondary form consists of a leukemic transformation in a previously recognized MM. In contrast to myeloma, PCL has an aggressive course. Median age at presentation is usually above 50 years. Here we report a case of primary PCL presenting at age of 21 years, which is extremely rare. She was treated with combination chemotherapy (VAD). Although she had a good response initially, later the disease progressed and she died 6 months after the diagnosis.

Key Words: Primary plasma cell leukemia, Multiple myeloma, Plasma cell dyscrasia.

Introduction

Plasma cell leukemia (PCL) is a rare form of plasma cell dyscrasia characterized by the presence of more than 20% plasma cells in peripheral blood and an absolute plasma cell count more than 2 × 10⁹ /L.¹ PCL can be of two types. The primary form presents de novo in patients with no previous history of multiple myeloma and usually features a rapid clinical progression and a short survival. The second type evolves as a terminal event in 12% of multiple myeloma.² Primary PCL is a distinct clinicopathological entity, because its clinical features, response to chemotherapy and prognosis are different from those of typical multiple myeloma. The median survival being as low as 6 month, it is very important to recognize this entity sufficiently early, so that one can offer combination chemotherapy at the earliest followed by stem cell transplant, which can prolong survival.³ Here we report a case of primary PCL, presenting at the age of 21 years, who responded to combination a chemotherapy regime of Vincristine, Cyclophosphamide and Dexamethasone.³ Although she had a good response initially, later the disease progressed and she died 6 months after the diagnosis.

Case Report

A 21-year-old female presented with complaints of loss of appetite and abdominal discomfort of 2 weeks duration. Patient was apparently normal prior to admission. She had purpuric spots over the hand and lower limb. On examination: She was pale, with upper cervical non-tender lymphadenopathy, tachycardia, elevated jugular venous pressure, a tender hepatomegaly and splenomegaly. Haemogram revealed a haemoglobin of 9.8g/dl, total white cell count of 14.8 x 10⁹/l and platelet counts was 40 x 10⁹/l. Peripheral smear showed hypochromia and anisopoikilocytosis, with 42% plasma cells and plasma blasts. Bone marrow aspirate showed 58% plasma cells and plasma blasts. Ultrasound scan of the abdomen was normal. Liver and renal function rests showed hypoalbuminemia, hyperphosphatemia and hyper uricemia. Serum protein electrophoresis (SPE) and immunofixation studies showed a immunoglobulin G (IgG) kappa paraprotein at a concentration of 3.7g/dl. Skeletal survey was normal. Flow cytometry of bone marrow aspirate showed intense positivity for CD 38 and the presence of cytoplasmic kappa light chains. Our patient was diagnosed to have primary PCL based on the findings of peripheral smear, bone marrow and flow cytometric analysis. She was started on chemotherapy regimen with vincristine, dexamethasone and adriamycin. After the first cycle of chemotherapy plasma cells in peripheral smear decreased to <10%. She received two more cycles of chemotherapy with the same regimen after which she was lost to follow up. Three months later she presented with similar symptoms and investigations showed progression of the disease. During reinduction chemotherapy, she succumbed to her illness, following an episode of septicemia.

Discussion

PCL is characterized by the presence of >20% plasma cells in peripheral blood.¹ By definition our patient had PCL. PCL can be considered as the leukemic variant of multiple myeloma. Its incidence ranges from 2% to 4% of all myelomas.^2,4,5 PCL has 2 variants the primary form arises de novo in patients with no previous incidence of multiple myeloma (constitutes 60%) and secondary form consists of a leukemic transformation in previously recognized multiple myeloma.⁵

Phenotypically they originate from proliferation of plasma cells expressing CD 38.⁶ Minority of cells expresses CD 10, HLA DR and CD 20. The presence of multiple haemopoietic surface antigens on malignant plasma cells suggests its origin from a pluripotent stem cell. Primary PCL shows higher expression of CD 20 as compared to multiple myeloma.⁴ Also, plasma cells from both primary and secondary PCL lacks CD 56, which is important in anchoring plasma cells to bone marrow stroma. More than 80% have a diploid/hypodiploid DNA content.⁴ Cytogenetic study shows complex karyotype with multiple numerical and structural abnormalities.² Up to 90% may show chromosome 13 monosomy.⁴Among Immunoglobulins, Ig G is most often increased.

Because of the low frequency of PCL, most of the data has come from case reports or small series of cases. In almost all the series median age ranged between 53 57 years (about 10 years younger than median age in myeloma series). The youngest age reported was 30 years.⁶ Primary PCL has a more aggressive course high frequency of extramedullary involvement (liver, spleen, lymph nodes, extra osseous plasmacytomas etc), thrombocytopenia, anemia, hypercalcemia and impaired renal function. Garcia-Sanz et al.⁴ has identified ten variables which have unfavorable prognostic value on the survival of primary PCL cases, of which serum Beta 2 microglobulin level > 6mg/L and S phase bone marrow plasma cells >4.5% retained an independent value on multivariate analysis.

Response to treatment of PCL is poor. Median survival is less than 1 year.² The longest survival reported was 28 months.⁵ The failure to achieve 50% clearance of blood plasma cells within 10 days after the initiation of treatment is a predictor of no response.³ Single alkylating agent with prednisolone is not appropriate for patients with primary PCL. Survival is significantly better in PCL patients treated with polychemotherapy as compared to melphalan and prednisolone.¹ Drugs used are vincristine, adriamycin, dexamethasone and/or cyclophosphamide and etoposide.³ Alternatively VCMP/VBAP is also used.⁶ Our patient showed marked improvement with VAD chemotherapy with >50% clearance of blood plasma cells within 10 days of starting the treatment of chemotherapy.

Since the prognosis is so poor, intensification of high dose chemotherapy followed by allogenic/autologous stem cell rescue should be tried.^6-8 Primary PCL requires such aggressive management so as to provide any survival advantage.

References

1. Grogan TM, Muller-Hermelink HK, Van CB, Harris NL, Kyle RA. World Health Organization Classification Tumours of Haematopoietic and Lymphoid Tissues. France: IARC Press Lyon; 2001.pp. 142-56.
2. Dimopoulos MA, Palumbo A, Delasalle KB, Alexaninan R. Primary plasma cell leukaemia. Br J Haematol 1994;88:754-9.
3. Hovenga S, de Wolf JThM, Klip H, Vellenga E. Consolidation therapy with autologous stem cell transplantation in plasma cell leukemia after VAD, high-dose cyclophosphamide and EDAP courses: A report of three cases and a review of the literature. Bone Marrow Transplant 1997;20:901-4.
4. Garcia-Sanz R, Orfao A, Gonzlez M, Tabernero MD, blade J, Moro MJ, et al. Primary Plasma Cell Leukemia: Clinical, Immunophenotypic, DNA Ploidy and Cytogenetic characteristics: Blood 1999;93:1032-7.
5. Noel P, Kyle RA. Plasma cell leukemia: An evaluation of response to therapy. Am J Med 1987;83:1062-8.
6. Costello R, Sainty D, Bouabdallah R, Fermand JP, Delmer A, Divine M, et al. Primary plasma cell leukemia: a report of 18 cases. Leuk Res 2001;25:103-7.
7. Mak YK, Chan CH, Chen YT, Lau SM, So CC, Wong KF. Consolidation therapy with autologous blood stem cell transplantation in a patient with primary plasma cell leukaemia. Clin Lab Haem 2003;25:558.
8. Ghosh K, Gosavi S, Pathare A, Madkaikar M, Rao VB, Mohanty D. Low cost autologous peripheral blood stem cell transplantation performed in a municipal hospital for a patient with plasma cell leukaemia. Clin Lab Haematol 2002;24:187-90.

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