|Year : 2014 | Volume
| Issue : 3 | Page : 111-114
Secondary plasma cell leukemia in a patient with light chain multiple myeloma in post-chemotherapy remission phase
Miguel Ángel Flores-Caballero, Dania Lizet Quintanilla-Flores, René Rodríguez-Gutiérrez
Department of Internal Medicine, University Hospital Dr. Jose Eleuterio Gonzalez, Monterrey, Nuevo León, México, USA
|Date of Web Publication||30-Sep-2014|
Dania Lizet Quintanilla-Flores
Department of Internal Medicine?, University Hospital Dr. José Eleuterio González, Av. Francisco I. Madero y Av. Gonzalitos, Col. Mitras Centro, Monterrey, Nuevo Leon, ZIP 64460, Mexico
Source of Support: None, Conflict of Interest: None
Plasma cell leukemia (PCL) is a rare presentation of multiple myeloma characterized by the presence of >20% plasma cells in peripheral blood, and an absolute plasma cell count >2 × 109 K/L. It is classified as primary and secondary with the latter representing a terminal event in 12% of patients. A case of a 78-year-old man who presented a secondary form of PCL during post-chemotherapy remission phase is discussed accompanied with a brief review.
Keywords: Multiple myeloma, secondary plasma cell leukemia, post-chemotherapy, remission phase
|How to cite this article:|
Flores-Caballero MÁ, Quintanilla-Flores DL, Rodríguez-Gutiérrez R. Secondary plasma cell leukemia in a patient with light chain multiple myeloma in post-chemotherapy remission phase. J Appl Hematol 2014;5:111-4
|How to cite this URL:|
Flores-Caballero MÁ, Quintanilla-Flores DL, Rodríguez-Gutiérrez R. Secondary plasma cell leukemia in a patient with light chain multiple myeloma in post-chemotherapy remission phase. J Appl Hematol [serial online] 2014 [cited 2020 Dec 5];5:111-4. Available from: https://www.jahjournal.org/text.asp?2014/5/3/111/142000
| Introduction|| |
Plasma cell leukemia (PCL) is an aggressive, uncommon presentation of multiple myeloma (MM), characterized by rapid progression and a poor prognosis with a prevalence ranging between 1% and 2% of all hematologic malignancies.  Diagnosis is based on the detection of >20% plasma cells in the peripheral blood as well as an absolute cell count in plasma >2 × 10 9 L. It is classified into two types: Primary PCL (pPCL), which occurs without a previous history of MM associated with a rapid progression and poor survival and which represents 60% of cases; and secondary (sPCL), which occurs as a progression of disease of MM, and represents a terminal event in 12% of cases. ,
Secondary PCL occurs as a progression of disease in 1-4% of all cases of MM. With a shorter overall survival compared to pPCL (1.3 months vs. 11.2 months), sPCL appears to have a 3:2 male:female sex distribution, and a median age at diagnosis of 50 years. , We present a rare case of sPCL associated with light chain MM.
| Case report|| |
The patient was a 78-year-old man with a history of benign grade IV prostatic hyperplasia, bladder stones, and JNC7-2 hypertension treated with captopril and nifedipine. He sought medical care because of a 1-year history of bowel changes characterized by constipation and abdominal distension as well as 3 months with generalized weakness, fatigue, asthenia, and adynamia. Fifteen days before admission he presented hematuria, oliguria, abdominal distension, weight loss (2 kg), and lower limb edema. During the initial evaluation hypercalcemia 18 mg/dL was detected, in addition to an altered state of consciousness. The patient was admitted to the hospital.
A complete blood count (CBC) and peripheral blood smear were performed, which reported a hemoglobin (Hb) 12.1 g/dL (12.2-18.1), a platelet count of 75.3 K/μL (142-424), and a leukocyte count of 19.9 K/μL (4.0-11.0) with a differential of 52% segmented neutrophils, 6% bands, 42% lymphocytes, and 6% atypical lymphocytes. The chemical profile reported creatinine 2.54 mg/dL (0.6-1.4); urea nitrogen 50.7 mg/dL (7-20); total protein 5.4 g/dL (6.1-7.9); albumin 3 g/dL (3.2-5.5), and globulin 2.4 g/dL (1.8-2.5). Serum electrolytes were repeated and hypercalcemia 18.55 mg/dL (8.4-10.2) was confirmed, with the rest being within normal parameters. Urinalysis showed proteinuria 100 mg/dL, erythrocytes + 100/field, and moderate epithelial cells and leukocytes 10-12/field.
As part of the study of hypercalcemia a bone marrow aspiration was performed, which detected 28% plasma cells; a bone marrow biopsy reported a malignant neoplastic proliferation of plasma cells. Serum immunoelectrophoresis reported hypoproteinemia secondary to hypogammaglobulinemia with no monoclonal peak, an IgG lambda restriction band, and a β2-microglobulin of 2.5 (normal < 3). On a plain abdominal CT lytic lesions were observed in the dorsal and lumbar vertebrae. Lytic lesions were also identified on plain X-rays of the skull and both iliac crests. Light chain multiple myeloma (MM) IIIB was diagnosed. Following 12 cycles of cyclophosphamide, dexamethasone and thalidomide, the patient went into clinical remission defined by the absence of a restriction band on immunoelectrophoresis and 5% plasma cells on bone marrow aspiration; maintenance therapy with thalidomide was then started.
Two months after achieving remission, he was again hospitalized because of fever, malaise, and epistaxis. A CBC showed leukocytosis 40,000 K/μL, anemia with Hb 7.6 g/dL, and thrombocytopenia 35.0 K/μL. A peripheral blood smear was performed that detected 30% plasma cells. With these features, PCL was diagnosed. An initial cycle of chemotherapy with vincristine, adriamycin and dexamethasone (VAD) was started. Three weeks later, the patient was readmitted because of severe dehydration, hemodynamic instability, acute confusional state and atrial fibrillation with a moderate ventricular response. The patient evolved poorly and died.
| Discussion|| |
We describe the clinical course of a male patient with a MM during the remission phase, who presented to our hospital with a suggestive diagnosis of sPCL. sPCL is an aggressive disease, mostly refractory to chemotherapy, with a prevalence ranging between 2% and 4% in patients with MM.  It generally develops during post-chemotherapy remission and/or bone marrow transplantation,  and is associated with a worse prognosis and a shorter life expectancy compared to patients with the primary form of PCL.  Median time to leukemic progression is 20.8 months from diagnosis to presentation of sPCL,  a fact similar to our patient, in which PCL occurred 18 months after diagnosis. sPCL has been associated to light chain MM in only 35% of reported cases, being de IgG subtype the most common reported protein,  similar to the presentation of our patient.
The etiology of its development is poorly understood; however, there are case reports that associated it with some forms of treatment such as radiotherapy and chemotherapy with melphalan  and alkylating agents,  or as part of the natural evolution of MM.  In contrast to MM, patients with sPCL present a more aggressive clinical course, more advanced stages (Stage III, Durie-Salmon) of clinical presentation, Bence Jones proteinuria at greater levels than MM, increased extramedullary involvement with hepatosplenomegaly, lymphadenopathy, and extramedullary plasmacytomas,  thrombocytopenia, anemia, hypercalcemia and chronic renal failure, ,,, with the last five being detected in our patient. Additionally, sPCL is associated with a higher prevalence of osteolytic lesions compared to pPCL (53% in sPCL and 18% in pPCL), as well as elevated LDH and β2-microglobulin and decreased serum albumin. ,
Clinically, it can manifest with low-grade fever, anorexia, nausea, dyspnea, weight loss, fatigue, anemia, abnormal bleeding, bone pain, and in some cases, as an acute confusional state. , Biochemically, it is characterized by anemia with Hb levels <9 mg/dL, thrombocytopenia with a platelet count <100 × 10 9 /L, and leukocytosis with ranges varying from 20 to >100 × 10 9 /L with 20-100% plasma cells.  Rouleaux formation is usually evident on the peripheral blood smear examination. 
The prognosis is highly variable, ranging from 2 to 6 months depending on the treatment used, with up to 28% patients dying within the 1 st month after diagnosis [Table 1]. ,, Given that the literature has reported improvement in survival when using bone marrow transplantation, treatment protocols include aggressive induction therapy followed by hematopoietic stem cell transplantation. Several induction regimens have been used, including alkylating agents, immunomodulatory agents and bortezomib.  Alkylating agents have been used as monotherapy and as induction therapy prior to bone marrow transplantation, achieving response rates of up to 45% and survival of 15.3 months. , Multi-agent infusional chemotherapy (e.g. vincristine, doxorubicin, dexametasone) result in a superior median survival rate compared to combinations that include melphalan. , Both thalidomide and lenalidomide have been used for the treatment of sPCL, with a temporally good initial efficacy, however the duration of response is brief, and generally with a short follow up duration, according to previous reports. 
Currently treatment with bortezomib and cyclophosphamide, either alone or in combination with dexamethasone have shown an increased life expectancy obtaining a progression-free survival of 8 months on average (range 0-26), with survival rates of 15 months (range 6-108). ,,, Moreover, bortezomib in combination with doxorubicin and dexametasone has been associated to both partial and complete response rates when used as salvage therapy in refractory cases of sPCL.  Unfortunately, as a developing country, it is common that our hospital doesn't have the resources to provide the best treatment in all of our patients. Our patient had a low socioeconomic status, unable to afford the high costs of a full treatment with bortezomib and cyclophosphamide when MM was diagnosed as well as when sPCL was detected, leaving CVT and VAD as our best choices. As expected, the response to treatment with alkylating agents was minimal, as evidenced by the progression of the disease culminating in the patient's death.
In general, median survival varies depending on the type of treatment as well as whether the diagnosis of pPCL or sPCL was made. When using conventional chemotherapy, it ranges from 7 to 14 months in pPCL and <2 months in sPCL. The use of hematopoietic stem cell transplantation as well as the introduction of combination therapy that includes bortezomib seems to improve survival in up to 16 months, especially in pPCL. 
| Conclusion|| |
Secondary plasma cell leukemia represents an aggressive proliferative disorder associated with a poor prognosis and a shorter survival compared to MM itself. Given that actual treatment of sPCL is unsatisfactory, novel therapeutic approaches are needed in order to improve outcome and quality of life in these patients.
| Acknowledgments|| |
Acknowledgments of technical help, the authors wish to thank Dr. Sergio Lozano for English translation.
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