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Year : 2022  |  Volume : 2  |  Issue : 2  |  Page : 133-137

Secondary plasma cell leukemia: A case series and review of the literature

1 Department of Hematology, HCG Manavata Cancer Centre, Nashik, Maharashtra, India
2 Department of Academics, HCG Manavata Cancer Centre, Nashik, Maharashtra, India
3 Department of Surgical Oncology, HCG Manavata Cancer Centre, Nashik, Maharashtra, India

Date of Submission31-Jan-2022
Date of Decision02-Oct-2022
Date of Acceptance04-Oct-2022
Date of Web Publication06-Feb-2023

Correspondence Address:
Dr. Sudarshan Pandit
Department of Hematology, HCG Manavata Cancer Centre, Nashik - 422 011, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpo.jpo_1_22

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Secondary plasma cell leukemia is a rare, aggressive plasma cell disorder with a poor prognosis. Early detection and prompt treatment can increase overall survival. In the current case series, we are reviewing the literature and retrospectively reporting the data of patients who presented to our center over a 3-year period with this rare condition. All of our patients were kept on induction chemotherapy following their initial diagnosis utilizing drug combinations that included cyclophosphamide, bortezomib, and dexamethasone (VTD chemotherapy). Further chemotherapy regimens were added during the later phases, including carfilzomib, pomalidomide, and dexamethasone as well as bortezomib, doxorubicin, and dexamethasone based on the outcome of the patient's response. This case study series emphasizes the significance of early disease detection and prompt supportive and targeted therapy.

Keywords: Case series, carfilzomib, pomalidomide, and dexamethasone chemotherapy, multidrug combinations, bortezomib, doxorubicin, and dexamethasone chemotherapy, Secondary plasma cell leukemia, VTD chemotherapy

How to cite this article:
Pandit S, Wasekar N, Badarkhe G, Bajaj R, Ramesh YV, Nagarkar R. Secondary plasma cell leukemia: A case series and review of the literature. J Precis Oncol 2022;2:133-7

How to cite this URL:
Pandit S, Wasekar N, Badarkhe G, Bajaj R, Ramesh YV, Nagarkar R. Secondary plasma cell leukemia: A case series and review of the literature. J Precis Oncol [serial online] 2022 [cited 2023 Mar 28];2:133-7. Available from: https://www.jprecisiononcology.com//text.asp?2022/2/2/133/369207

  Introduction Top

Plasma cell leukemia (PCL) is a rare and aggressive hematological condition characterized by the presence of circulating plasma cells of at least 2.0 × 109/L or >5%–20% in the peripheral blood.[1] PCL forms 2%–4% of all myelomas with a median age of 50 years at diagnosis. It was also found to be predominant in males over females, with a distribution ratio of 3:2.[1],[2],[3],[4] PCL is classified in to two forms – primary PCL (pPCL) and secondary PCL (sPCL). In pPCL, the leukemic phase presents at diagnosis without preceding multiple myeloma (MM); and sPCL corresponds to the leukemic transformation of previously diagnosed MM.[2] In PCL, 60% of the patients have pPCL, and the rest 40% with sPCL. In recent times, there is an increase in sPCL patients due to more effective therapies contributing to both clonal selections over time and improved survival.[1] PCL is a leukemic variant of MM with a poor prognosis, with median overall survival of 11.2 months in pPCL patients and 1.3 months in sPCL patients, respectively.[5] A total of 28% of people die within the 1st month of diagnosis with PCL.[3] Therefore, the most significant lifesaving factors for better prognosis in such patients include prompt diagnosis and early treatment with supportive and targeted therapy.

Most of the literature available on PCL is either case reports or case reviews due to its rarity. Because long-term studies are not feasible in PCL, the literature on sPCL is substantially more limited. Individual case reports and case series can aid in the advancement of therapeutic options for difficult and challenging diseases like sPCL, where there are no clinical trials. This case series of sPCL is being documented and discussed to supplement the literature for future studies and to enhance the clinical, diagnostic, and therapeutic knowledge of the disease.

  Case Report Top

Case 1

A 71-year-old male was presented with complaints of double vision, progressive swelling, and a decrease in left eye vision for 45 days. Clinical and biological data are presented in [Table 1]. Imaging studies (magnetic resonance imaging) were performed, revealing severely bulky left medial rectus with soft-tissue enhancement in perioptic and retrobulbar region. Mass effect was noted in the intraorbital optic nerve in its posterior half. The patient underwent transethmoidal endoscopic biopsy of the left orbital mass, followed by histopathology suggesting plasma cell neoplasm. Serum protein electrophoresis was suggestive of M band-2.68 in the gamma region.
Table 1: Clinical and biologic data of patients diagnosed with secondary plasma cell leukemia

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The tumor cells were found to be immunohistologically positive for MUM1, CD138, and kappa restricted proteins. Bone marrow aspirate and biopsy were consistent with plasma cell neoplasm. Positron emission tomography-computed tomography was suggestive of metabolically active soft tissue in the medial aspect of the left orbit.

Cytogenetics on bone marrow aspirate revealed monosomy 13 in 95% of cells and 1q21 amplification in 90% of cells. As a result, a highrisk case of MM with extramedullary involvement of the left orbit was diagnosed as part of the International staging system (ISS) III. The patient was started on standard cyclophosphamide, bortezomib, and dexamethasone (VTD) chemotherapy. During VTD chemotherapy, the patient relapsed with 28% plasma cells on the peripheral smear. A diagnosis of sPCL was made, and the patient died within a week as a result of the condition.

Case 2

A 67-year-old male with a history of MM-IGG-LAMBDA-ISS IIIB was presented to our center [Table 1]. Cytogenetics showed 13q and t (11;14) positive. The patient was started on standard VTD chemotherapy. After 11 cycles of VTD chemotherapy, the patient was kept on dexamethasone maintenance. A follow-up bone marrow aspiration and biopsy were carried out and the results showed a complete response (CR). Based on the previous reports, the patient was initiated on carfilzomib, pomalidomide, and dexamethasone (KPD) chemotherapy. The patient developed a pomalidomide-induced drug rash all over the body. Pomalidomide was withdrawn while treated with steroids showing a complete recovery from the drug-induced rash.

The patient defaulted to therapy for 3 months. During the follow-up for the next KPD chemotherapy, the patient had a relapse with 22% plasma cells on the peripheral smear. A diagnosis of sPCL was made. The patient was planned for bortezomib, doxorubicin, dexamethasone (PAD) chemotherapy and completed two cycles of it. During follow-up, the patient succumbed to acute renal failure and severe hyponatremia.

Case 3

A 68-year-old female, a known case of stage III MMISS with high risk, repoirted to our center. The examination indicated fluorescent in situ hybridization, which confirmed a positive status for t(11;14): IGH/CCND1 gene translocation in 60% of the interphase cells examined [Figure 1]. The patient was initiated on four cycles of standard VTD chemotherapy. Due to coronavirus disease (COVID-19), pandemic regulations, and lockdown, the patient defaulted therapy for 6 months. On follow-up, complete blood count was suggestive of leukocytosis with peripheral blood smear showing relapse with 32% plasma cells suggesting sPCL [Table 1]. The patient was informed of the poor prognosis and treatment outcomes. The patient delayed treatment, was lost to follow-up, and ultimately perished.
Figure 1: Fluorescence in situ hybridization analysis showed positive status for t(11;14): IGH/CCND1 Gene translocation in 60% interphase cells analyzed in one of the patient (case 3). (a) Interphase cell showing 1 Fusion (yellow), 2 Orange (11q23), 2 Green signals (14q32) indicative of positive status for t (11;14): IGH/CCND1 gene translocation, (b) Interphase cell showing 2 Orange signals (11q22.3) is indicative of normal diploid status for chromosome 11q, (c) Interphase cell showing 2 Orange, 2 Green signals indicative of t (14q32): IGH gene rearrangement positive status with variant pattern (F = Fusion signals [Intact allele of IGH gene]), (d) Interphase cell showing 2 Orange (4p16), 3 Green signals (14q32) indicative of negative status for t (4; 14): IGH/FGFR3 gene rearrangement but showed break in IGH gene, (e) Interphase cell showing 2 Orange (LSI TP53 (17p13.1), 3 Green signals indicative of negative status for t (14;16): IGH//MAF/WWOX gene rearrangement but showed break in IGH gene, (f) Interphase cell showing 2 Orange signals (LSI TP53 (17p13.1) indicative of del (17p13) negative status, (g) Interphase cell showing 2 Orange (1q21) and 2 Green signals (1p32) indicative of chromosome 1p/q deletion/amplification negative status, (h) Interphase cell showing 2 Aqua (5p), 2 Orange (9q) and 2 Green signals (15q) indicative of normal diploid status for chromosome 5p/q, 9q and 15q, (i) Interphase cell showing 2 Orange (13q14), 2 Green signals (13qter) indicative of del (13q) negative status

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  Discussion Top

sPCL is the leukemic transformation of prediagnosed MM and is reported in 1%–4% of all MM cases.[2] As per previous reports, the male-to-female sex distribution in sPCL appeared to be 3:2 (in our patients 2:1) with a median age of 67 years (in our patients ~68.5 years) on the diagnosis.[2],[6],[7] Among our three patients, two patients were presented with confirmed MM and 1 with progressive swelling of the eye. Other than typical symptoms of MM, extramedullary and extra-osseous symptoms were not reported in our patients on presentation. Additionally, plasma cell morphology is extremely typical. Where small to medium-sized cells with basophilic cytoplasm, perinuclear hof, and infrequent binucleation were observed [Figure 2].
Figure 2: Peripheral blood smear showing small-to-medium size circulating plasma cells (a-e); basophilic cytoplasm with perinuclear hof (e) and occasional binucleated plasma cells (b)

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Clinically and biologically, MM, pPCL, and sPCL are three distinct entities. Among them, sPCL prognosis is reported to be very low, especially in patients with advanced relapsed or refractory myeloma. Except for CD 28, sPCL is an accumulation of multiple genetic changes sharing several similar immunophenotypic expressions with PCL and MM, such as CD 15, CD 13, CD 10, CD 16, CD 3, CD 2, CD 138, and CD 38. The presence of CD 28 represents the poor prognosis, chemotherapy resistance, disease progression, and plasma cell proliferation. spcl also shares some similar immunophenotypic features with pPCL with respect to lack of leukocyte function-associated antigen 1, neural cell adhesion molecule, human leukocyte antigen (HLA DR), CD 117, CD 71, CD 56, CD 45, CD 44, CD 23, CD 20, CD 9, 1q21 amplification, 1p21 deletion, 17 P deletion, MYC translocations/amplification, and IgH translocations.[1],[2],[3],[4],[6],[7],[8] Among all chromosomal and gene translocations, 14q32 and CCND1 were found to be high in sPCL patients, and these anomalies were also found in our patients.

Due to the absence of a recognized curative regimen, chemotherapy is generally used after an initial evaluation and confirmation of the disease in order to maximize the quality of life and prolong the survival period.[2],[9] Such chemotherapy regimens are divided into three phases as induction, consolidation, and maintenance. All the patients will be first initiated on induction therapy, and the drug combination is highly varied from patient to patient depending on the disease severity. Such induction therapy regimens include alkylating agents, immunomodulatory agents (lenalidomide, pomalidomide, etc.,), and proteasome inhibitors (bortezomib).

For better outcomes, multi-regime therapies are highly recommended during all the phases of chemotherapy, such as bortezomib, doxorubicin, and dexamethasone (PAD), cyclophosphamide, bortezomib, dexamethasone (CyBorD), bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide (VDT-PACE), carfilzomib, lenalidomide, dexamethasone (KRd) or bortezomib, lenalidomide, and dexamethasone VRd, and high-dose cyclophosphamide, vincristine, adriamycin, and thalidomide or lenalidomide (HyperCVAD).[1],[4] Among all the regimens, the most preferred regimen for induction therapy is KRd and VRd.[3],[4],[8] Whereas VDT-PACE or HyperCVAD are recommended in patients with aggressive disease.[4],[8] PAD or CyBorD is suggested in elderly and frail patients, as a milder alternative.[3],[4],[8] Consolidation with autologous stem cell transplantation (ASCT) is recommended only after postinduction chemotherapy.[2],[8] Throughout almost all chemotherapy regimens, bortezomib tends to be recommended and incorporated as a single agent or in combination with other chemotherapies due to the fact that its response rate and median survival rate are extremely high.[2]

Based on the previous study reports and support, induction chemotherapy in our patients was also initiated using VTD regimen. Whereas in a patient with CR from induction chemotherapy, KPD and PAD regimens were initiated as per protocols. Due to relapse or lost/irregular follow-up or due to chemotherapy-induced fatal effects, all our patients have succumbed to death within weeks of time with a survival rate of zero.[1],[3],[4],[6],[10]

To overcome these early deaths, relapses, and limitations with previous regimens, new therapies such as venetoclax (B-cell lymphoma-2 inhibitor),[10] chimeric antigen receptor (CAR) T-cell therapy,[11] high-dose melphalan before ASCT (NCT01729091),[2] immunotherapies (e.g., antibody-drug conjugates,[12] bi-specific T-cell engagers[13]), bb2121 (phase I, B-cell maturation antigen-targeted CAR T-cell),[11] panobinostat in combination with mAbs,[4] natural killer (NK) cells in combination with lenalidomide, elotuzumab (phase II), NCT02506959 (melphalan, busulfan, gemcitabine, and panobinostat before ASCT),[14] and use of selinexor[15] into multi-agent regimens emerged as a hope. However, large clinical trials are warranted to establish the safety and efficacy of these novel therapies.

From our experience, we suggest that in this difficult-to-treat population of pPCL and sPCL-treatment should always be tailored based on the patient's profile. Tailored personalized medicine is always proven to be highly efficient in providing the right treatment at the right time with the right drug.[16]

A long-term prospective study/clinical trial on these patients is not feasible at this time, so limited data are available for guiding treatment for sPCL. In such scenarios, information extrapolated from these case reports, case series, and retrospective reports can be highly beneficial in providing a better insight into diagnosis, etiopathology, treatment protocol, and overall disease management.

  Conclusion Top

Our observations suggest that sPCL is a rare, aggressive proliferative disease with life-threatening complications and a limited survival period. Therefore, intensive treatment using multidrug combinations is recommended as a rational approach. For some of these immunophenotypic and genetic characteristics to be overcome, it is recommended to combine high-dose therapy with novel agents. As the treatment for sPCL is not satisfactory, novel therapeutic approaches may hold promise as a means of improving the quality of life and outcome for these patients. In all of our patients, defaulting treatment and loss of follow-up were observed as major causes of prior death.

Patient permission

Patient permission for using data and photographs was obtained.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


The authors would like to thank Dr. Yasam Venkata Ramesh from HCG Manavata cancer centre, Centre for difficult cancers (CDC), Nashik, India, for his medical writing assistance.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Table 1]


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