Successful treatment with bortezomib-containing regimen of primary plasma cell leukemia: a case report

Plasma cell leukemia represents the most aggressive form of plasma cell dyscrasia. We report a 67-year old male with no previous medical illnesses presented with anemic symptoms. Blood film revealed 35% circulating plasma cells, bone marrow biopsy showed plasma cells constituting 85%. Diagnosis of primary plasma cell leukemia was completed. Induction chemotherapy with bortezomib, doxorubicin, and dexamethasone was started. After the first cycle, plasma cells in peripheral blood disappeared. The patient had complete remission at evaluation after the third cycle. Re-evaluation after the sixth cycle showed that he maintained remission. As he was non-transplant eligible, he was we kept on maintenance bortezomib. Twenty-four months after the diagnosis, the patient remains in remission.


Introduction
Plasma cell leukemia (PCL) represents the most aggressive form of plasma cell dyscrasia. The incidence is thought to be less than 1 case/million [1]. It is divided into primary plasma cell leukemia (pPCL) which constitutes about 60% of cases, which occurs de novo without evidence of the previous history of plasma cell disorder. While secondary plasma cell leukemia (sPCL) represent progression and leukemic transformation in a patient previously diagnosed with multiple myeloma (MM). The prognosis of pPCL is poor with median survival reported being 2 to 8 months [2]. The diagnosis requires peripheral plasma cells of more than 2×10 9 /L or a greater than 20% of leukocyte count [3]. We present a patient diagnosed with pPCL who achieved complete remission after induction chemotherapy with bortezomib, doxorubicin and dexamethasone followed by maintenance bortezomib as he was non-transplant eligible.

Patient and observation
A 67-year old male previously healthy was admitted in January 2018 to our hospital with fatigue, dyspnea on effort and multiple bone pains. The physical examination was unremarkable except for pallor and mild splenomegaly. Initial laboratory investigations showed macrocytic anemia with a hemoglobin of 9.9 g/dl, white blood cell count of 19.4x10 3 /μl and platelet count was 77x10 3

PCL was first described in 1906 by Professor Gluzinski and
Dr. Reichenstein who established the first diagnostic criteria for PCL: plasma cells circulating in the peripheral blood (CPCs) of more than 2×10 9 /L or a greater than 20% of the peripheral blood leukocyte count. This definition has lots of drawbacks; first, it requires a high number of CPCs in peripheral blood detected with conventional count for diagnosis. Many patients with a level <20% threshold may have similar outcomes to those with = 20% CPCs [5]. Second, the diagnosis of PCL is operator dependant; it needs for hematologist or pathologist to count CPC by light microscope. Thus, diagnosis with immunophenotyping by Multiparameter Flow Cytometry is warranted.
Lastly, the definition didn't differentiate between pPCL which occurs de novo and sPCL which consider being a leukemic progression of MM. Therefore, the International Myeloma Working Group (IMWG) announced for studies to revise criteria for the diagnosis of PCL [6].
There is no standard therapeutic strategy for the treatment of PCL as most of the information about PCL has been extrapolated from case reports, case series, and retrospective reports. There were very few prospective studies that evaluated the best management for PCL. The remission. This could be followed by maintenance with novel agents.
While in patients who are considered to be non-transplant eligible whether because of advanced age or comorbidities the benefits of maintenance treatment after induction of remission is highlighted, precautions should be made in these patients to prevent infections with prophylaxis antibiotics, antiviral and antifungal because of their remarkably impaired immune system. Also, prophylaxis with allopurinol is essential because these patients are prone to tumor lysis syndrome [7]. Bortezomib-based regimens show promise as induction regimens for PCL. A large multicenter retrospective survey conducted by the GIMEMA group in 2012 focused on pPCL patients who had received bortezomib exclusively as frontline therapy. Twenty-nine patients with pPCL were collected. An overall response rate of 79% was observed, after a median follow-up of two years, the progressionfree survival (PFS) was 55% [8]. Another multicenter retrospective study included 73 patients with pPCL, different regimens were examined, and the best outcome was for patients who treated with bortezomib-based regimens followed by autologous stem cell transplantation (ASCT) [9]. Based on the above results we started induction chemotherapy with a bortezomib-based regimen. ASCT has been widely used in the treatment of transplant-eligible patients with pPCL aiming to achieve a deep response and prolong remission.
Patients with pPCL not eligible for ASCT, the induction therapy should be followed by maintenance regimens which can include either bortezomib or lenalidomide or both [10]. So, our patient was kept on maintenance bortezomib till progression.

Conclusion
Our case demonstrates a potentially curative strategy (and relatively well-tolerated) for newly diagnosed transplant-ineligible pPCL with a combination of bortezomib, doxorubicin, and dexamethasone in the induction phase, followed by maintenance bortezomib.

Competing interests
The authors declare no competing interests.

Authors' contributions
The contribution of each author is quantified as below: Mohammad