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Year : 2018  |  Volume : 14  |  Issue : 6  |  Page : 1431-1433

Development of plasma cell leukemia in a patient with chronic myeloid leukemia while on treatment with imatinib mesylate

1 Department of Hematology, Ankara Ataturk Training and Research Hospital, Ankara, Turkey
2 Department of Hematology, Yildirim Beyazit University, Ankara, Turkey

Date of Web Publication28-Nov-2018

Correspondence Address:
Senem Maral
Department of Hematology, Ankara Ataturk Training and Research Hospital, Lodumlu, Bilkent 06800, Ankara
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.192762

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 > Abstract 

Plasma cell leukemia (PCL) is a rare and an aggressive form of plasma cell dyscrasias. We report a 67-year-old male with PCL which developed while on imatinib mesylate (IM) therapy 38 months after diagnosis of chronic myeloid leukemia (CML). The patient has been treated successfully with bortezomib, melphalan and prednisolone. To our knowledge, only one case of PCL superimposed on Philadelphia positive CML has been reported in the literature and this was before the IM era.

Keywords: Chronic myeloid leukemia, plasma cell leukemia, tyrosine kinase inhibitors

How to cite this article:
Maral S, Bakanay SM, Yikilmaz AS, Dilek I. Development of plasma cell leukemia in a patient with chronic myeloid leukemia while on treatment with imatinib mesylate. J Can Res Ther 2018;14:1431-3

How to cite this URL:
Maral S, Bakanay SM, Yikilmaz AS, Dilek I. Development of plasma cell leukemia in a patient with chronic myeloid leukemia while on treatment with imatinib mesylate. J Can Res Ther [serial online] 2018 [cited 2020 May 27];14:1431-3. Available from: http://www.cancerjournal.net/text.asp?2018/14/6/1431/192762

 > Introduction Top

Plasma cell leukemia (PCL) is a rare and aggressive form of plasma cell dyscrasias, characterized by the presence of >:2 × 109/L circulating plasma cells or plasmacytosis accounting for >:20% of peripheral blood leukocytes. The coexistence of chronic myeloid leukemia (CML) and plasma cell dyscrasia is an extremely rare event. It has been over a decade since imatinib mesylate (IM) has become the gold standard first-line treatment for CML. Although IM has been regarded as a safe drug, there are still unknowns on its long-term toxicity. To our knowledge, there are only three cases of multiple myeloma (MM) development on IM therapy and only one case of PCL developing in a CML patient before IM era.[1],[2],[3],[4]

 > Case Report Top

A 67-year-old male was admitted with leukocytosis on December 2011. His initial complete blood count was white blood cell (WBC) 21 × 109/L, Hb 12.8 g/dL and platelets 270 × 109/L. Serum protein level was 7.1 g/dL, and albumin was 4.7 g/dL. The peripheral blood smear was consistent with chronic phase CML and a reverse transcription polymerase chain reaction from peripheral blood revealed positive for BCR/ABL transcript. The patient was started IM 400 mg/day. Three months after diagnosis, hematological response was observed. However, the patient was incompliant with the therapy because of peripheral edema and gastrointestinal intolerance, and a major molecular response (MMR) could only be achieved at the end of the 3rd year with an IS of 0.02%. In August 2015, he admitted with progressive fatigue and a decrease in the Hb level. He had WBC 18.6 × 103/L, neutrophil 2.4 × 103/L, lymphocyte 7.9 × 103/L, monocyte 7.9 × 103/L, Hb 6.1 g/dL, platelets 118 × 103/L, and erythrocyte sedimentation rate 122 mm/h. In the peripheral smear, plasma cells constituted about half of the WBC [Figure 1]. Flow cytometry revealed clonal plasma cells positive for CD38, CD138, CD117, CD56, and cytoplasmic kappa light chain. Bone marrow was infiltrated with pleomorphic plasma cells with similar immunohistochemical staining. Serum protein electrophoresis was normal, and serum immunofixation did not reveal any monoclonal protein. However, urinary immunofixation was consistent with possible monoclonality in the kappa light chain region. The interphase fluorescence in situ hybridization demonstrated del13q14.3 and t(11;14) IgH/CCND1 positivity. At the time of PCL diagnosis, the patient was still in MMR with an IS of 0.01%.
Figure 1: Peripheral smear, image ×100

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The patient was not eligible for high-dose therapy due to low performance status. He was started versus bortezomib, melphalan and prednisone regimen (melphalan 8 mg/m2/day 1–4 days, bortezomib 1.3 mg/m2/day days 1, 4, 8, 11; and prednisolone 60 mg/m2/day) and IM was continued. However, by the end of the second cycle, he had two admissions to the emergency service because of paralytic ileus which responded to supportive therapy. At the following cycles, IM was omitted on the days of chemotherapy and bortezomib was given once weekly. The patient did not experience any ileus episodes. He has received the 6th cycle of chemotherapy and responded by complete disappearance of plasma cells in the bone marrow and negative urine immunofixation.

 > Discussion Top

Our patient developed PCL 38 months later while on IM therapy for CML. To our knowledge, this is the second case of PCL preceded by CML. The first reported patient was before the IM era.[4] Since our case was in MMR at the time of PCL diagnosis, the possibility of malignant transformation of a common pluripotent stem cell is weakened. On the other hand, an association of IM with the development of plasma cell dyscrasias cannot be ruled out. IM has been associated with both positive and negative effects on plasma cell proliferation. In one study, imatinib exhibited a small stimulatory effect on the proliferation of MM cells through the Erk1/2 mitogen-activated protein kinases pathway.[5]

Tyrosine kinase inhibitors are known to interfere with T-cell and B-cell receptor signal transduction resulting in negative effects on B-cell proliferation and function. This may be responsible from the hypogammaglobulinemia commonly observed in CML patients treated with IM.[6] Carulli et al. have demonstrated that a significant percentage of the CML patients treated with IM displayed an abnormal plasma cell phenotype characterized by the lack of CD19 expression and in most cases the absence of CD45 and presence of CD56 expression.[7]

Because of the rarity of the disease, sufficient data on the treatment of primary PCL is lacking. However, studies have suggested that bortezomib, alone or in combination with other agents, induces better responses and prolongs survival, especially overcoming the poor prognosis conferred by del13q.[8] Based on this knowledge, we preferred using a bortezomib-based regimen for our patient. On the other hand, we could not find any information in the literature about coadministration of IM and bortezomib. In vitro data from cell lines were presented at the 2001 ASH meeting by Gatto et al. who concluded that coadministration of the two drugs might be feasible.[9] Three cases of MM have been reported to have developed during IM treatment for CML. Two of these cases received melphalan and prednisolone for myeloma and IM was continued.[2],[3] On the other hand, the third case received Vincristin, Adriamycine, Dexamethasone (VAD) regimen and IM was deferred.[1]

The patient experienced episodes of paralytic ileus during the first two cycles. Gastrointestinal adverse events are commonly observed with the use of bortezomib. Rarely, severe constipation and paralytic ileus associated with bortezomib have been reported. Fukushima et al. have reported that the incidence of gastrointestinal adverse events was lower when the drug is administered once weekly rather than twice weekly.[10] Microsomal enzyme CYP3A4 plays an important role in the metabolism of both bortezomib and IM. Human liver microsomal studies revealed that IM is a potent and bortezomib is a weak inhibitor of CYP3A4. Coadministration of bortezomib and IM might have resulted in increased exposure to bortezomib probably increasing the risk of paralytic ileus. It is noteworthy that the patient did not experience any adverse event when bortezomib was administered once weekly.

 > Conclusion Top

Plasma cell dyscrasias which have been occasionally reported in patients with CML are generally regarded as coincidental. The contribution of tyrosine kinase inhibitors in the development of plasma cell dyscrasias requires further investigation. Coadministration of bortezomib-based regimens and IM may be feasible. However, caution should be taken since IM may increase bortezomib exposure and precipitate severe adverse events. Once weekly administration of bortezomib may overcome the results of this interaction and prevent unnecessary cessation of IM.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Michael M, Antoniades M, Lemesiou E, Papaminas N, Melanthiou F. Development of multiple myeloma in a patient with chronic myeloid leukemia while on treatment with imatinib mesylate for 65 months. Oncologist 2009;14:1198-200.  Back to cited text no. 1
Garipidou V, Vakalopoulou S, Tziomalos K. Development of multiple myeloma in a patient with chronic myeloid leukemia after treatment with imatinib mesylate. Oncologist 2005;10:457-8.  Back to cited text no. 2
Galanopoulos A, Papadhimitriou SI, Kritikou-Griva E, Georgiakaki M, Anagnostopoulos NI. Multiple myeloma developing after imatinib mesylate therapy for chronic myeloid leukemia. Ann Hematol 2009;88:281-2.  Back to cited text no. 3
Sakai A, Kawano M, Oguma N, Kuramoto A. A case of plasma cell leukemia superimposed on Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia. Am J Hematol 1991;36:222-3.  Back to cited text no. 4
Pandiella A, Carvajal-Vergara X, Tabera S, Mateo G, Gutiérrez N, San Miguel JF. Imatinib mesylate (STI571) inhibits multiple myeloma cell proliferation and potentiates the effect of common antimyeloma agents. Br J Haematol 2003;123:858-68.  Back to cited text no. 5
Steegmann JL, Moreno G, Aláez C, Osorio S, Granda A, de la Cámara R, et al. Chronic myeloid leukemia patients resistant to or intolerant of interferon alpha and subsequently treated with imatinib show reduced immunoglobulin levels and hypogammaglobulinemia. Haematologica 2003;88:762-8.  Back to cited text no. 6
Carulli G, Cannizzo E, Ottaviano V, Cervetti G, Buda G, Galimberti S, et al. Abnormal phenotype of bone marrow plasma cells in patients with chronic myeloid leukemia undergoing therapy with Imatinib. Leuk Res 2010;34:1336-9.  Back to cited text no. 7
D'Arena G, Valentini CG, Pietrantuono G, Guariglia R, Martorelli MC, Mansueto G, et al. Frontline chemotherapy with bortezomib-containing combinations improves response rate and survival in primary plasma cell leukemia: A retrospective study from GIMEMA multiple myeloma working party. Ann Oncol 2012;23:1499-502.  Back to cited text no. 8
Scappini B, Gatto S, Onida F, Ricci C, Divoky V, Wierda WG, et al. In vitro effects of PS-341 alone and in combination with STI571 in Bcr-Abl positive cell lines both sensitive and resistant to STI571. Blood 2001;98 Suppl 11:101a.  Back to cited text no. 9
Fukushima T, Nakamura T, Iwao H, Nakajima A, Miki M, Sato T, et al. Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: Once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. Anticancer Res 2011;31:2297-302.  Back to cited text no. 10


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