Primary plasma cell leukemia: a case report

¹Hematology Laboratory, Mohammed VI University Hospital, Oujda, Morocco, ²Faculty of Medicine and Pharmacy, Mohammed the First University, Oujda, Morocco

^&Corresponding author
Asmae Kidoun, Hematology Laboratory, Mohammed VI University Hospital, Oujda, Morocco

Introduction    

Plasma cell leukemia (PCL) is a rare and aggressive subtype of multiple myeloma (MM). Two forms are distinguished: the primary form, which occurs de novo, and the secondary form, which complicates previously known multiple myeloma. The International Myeloma Working Group (IMWG) established in 2021 a new criterion defining blood plasmacytosis as a plasma cell count >5% of the leukocyte differential; patients with plasmacytosis between 5 and 20% are eligible for treatments and clinical trials for "aggressive myeloma" [1]. Plasma cell leukemia (PCL) is characterized by an aggressive clinical presentation, with frequent extramedullary localization and more severe biological abnormalities (anemia, thrombocytopenia, renal failure, and hypercalcemia) than in MM. Despite the emergence of new therapies coupled with hematopoietic stem cell transplantation, PCL remains an extremely challenging disease in terms of prognosis [2]. We report a case of primary PCL recently diagnosed in the Hematology Department of Mohammed VI University Hospital, Oujda, Morocco.

Patient and observation     

Patient information: a 67-year-old man with a history of untreated arterial hypertension, diet-controlled diabetes, benign prostatic hypertrophy under treatment, and previous appendectomy, presented to the emergency department of Mohammed VI University Hospital, Oujda, Morocco. His chief complaint was a hemorrhagic syndrome consisting of epistaxis and gingivorrhagia, combined with an anemic syndrome with altered general condition.

Clinical findings: on clinical examination, the patient was febrile (38.8°C) with tachypnea, cutaneous and mucosal pallor, and declive purpura. Cervico-thoraco-abdomino-pelvic CT scan demonstrated osteolytic lesions of vertebral bodies D9 and D10.

Timeline: day 1: admission for hemorrhagic and anemic syndrome with fever (38.8°C). Day 1-2: Biochemical workup revealing hypercalcemia (110 mg/L), renal failure (creatinine 25.47 mg/L), elevated beta-2-microglobulin (17.12 mg/L), LDH elevation (3325 IU/L), and suspicious beta-1 globulin peak on protein electrophoresis (Figure 1). Day 2: serum and urine immunofixation confirming monoclonal lambda free light chain (Figure 2). Day 2-3: blood count showing macrocytic aregenerative anemia (Hb 7 g/dL), thrombocytopenia (34 G/L), and blood smear with 19% plasma cells (3,760/mm³) (Figure 3). Day 3: bone marrow aspirate revealing 87% infiltration by dystrophic plasma cells (Figure 4). Day 4: diagnosis of primary light-chain plasma cell leukemia. Day 5+: initiation of PAD chemotherapy (bortezomib, doxorubicin, dexamethasone).

Diagnostic assessment: biochemistry revealed hypercalcemia (110 mg/L), creatinine (25.47 mg/L), beta-2-microglobulin (17.12 mg/L), LDH (3325 IU/L), and a suspicious peak migrating into the beta-1 globulin zone with hypogammaglobulinemia on serum protein electrophoresis (Figure 1). Serum immunofixation revealed a clear band of very high intensity isolated only at lambda level, with no correspondence at IgG, IgA, IgM, IgD, or IgE level; urine immunofixation also confirmed a lambda-type free light chain (Figure 2). The blood count showed macrocytic aregenerative anemia (hemoglobin 7 g/dL) and thrombocytopenia (34 G/L). The blood smear revealed 19% plasma cells, equivalent to 3,760/mm³ (Figure 3). The myelogram revealed 87% infiltration by highly dystrophic plasma cells, including numerous immature forms (plasmoblasts, pro-plasmocytes) (Figure 4). The main diagnostic challenge was the unusual presentation with lambda free light chain type, found in 41% of primary PCL cases in the Tiedemann series. [3] On the basis of these clinicobiological findings, the diagnosis of primary light-chain plasma cell leukemia was established. Immunophenotyping was not performed in this case.

Therapeutic interventions and follow-up: the patient was treated with PAD chemotherapy combining bortezomib, doxorubicin, and dexamethasone. This regimen was chosen given the patient's age, performance status, and the urgency of the clinical situation. No allogeneic or autologous stem cell transplantation was performed at initial presentation. Follow-up data beyond initial chemotherapy initiation are not available for this report.

Patient perspective: the patient's formal perspective could not be obtained for this case report. The patient was critically ill at admission and diagnosis, and formal assessment of his treatment experience was not conducted. The manuscript has been fully anonymized in accordance with journal and institutional policy.

Informed consent: formal written informed consent from the patient could not be obtained for the following reasons: the patient died during hospitalization before consent could be formally requested, and despite reasonable efforts, no next of kin or legal representative could be identified or contacted. In accordance with the ethical principles governing the publication of case reports involving deceased patients, and consistent with the Declaration of Helsinki, this case is reported solely for its significant scientific and educational value. All patient data have been fully anonymized: no names, initials, exact dates, or other identifying information are included in the manuscript text or figures. The manuscript has been reviewed and approved by the authors in accordance with institutional ethical standards applicable to retrospective case reports.

Discussion     

Plasma cell leukemia accounts for 1-2% of plasma cell neoplasias and is characterized by malignant proliferation of plasma cells responsible for peripheral blood plasmacytosis >0.5 G/L or >5% of leukocytes [2]. It can be primary in 50–70% of cases, occurring at a median age of 55 years, younger than secondary PCL (median 66 years). The classic clinical presentation associates asthenia, bone pain, anemia, and hemorrhagic syndrome, with a more aggressive course than MM, including frequent extramedullary involvement of the liver (52%) and spleen (40%) in primary PCL [4]. Lytic bone lesions occur in 40-60% of cases, lower than in MM. Careful cytological examination of the blood smear is crucial for diagnosis; anemia is present in 90% of cases, and myelogram reveals diffuse plasma cell infiltration (50–100%), often with dystrophic features [2]. In the Tiedemann et al. series [3], a free light chain alone was detected in 41% of primary PCL cases and 31% of secondary PCL cases. Our patient presented lambda free light chain type. Hyperexpression of CD38 and CD138 is frequent; increased CD20 expression and loss of CD56 have been proposed as discriminant markers by the IMWG, though immunophenotyping was not performed in our case.

Treatment depends on age, clinical context, and biological parameters. Historical regimens (melphalan-prednisone, VAD, VBAP) yielded overall response rates of 23-67% with median overall survival under 1 year, as documented in early North African case series.[5,6]. Autologous stem cell transplantation remains the treatment of choice for eligible patients under 65; the CIBMT study (79 primary PCL cases, 1995-2006) reported 3-year progression-free survival of 34% and overall survival of 64% [7].

Novel agents (bortezomib, carfilzomib, lenalidomide, thalidomide) and immunotherapy (CAR-T cells, daratumumab) have improved prognosis and quality of life [8,9]. Since our patient's diagnosis, the European Myeloma Network published its first dedicated consensus on primary PCL (2025), confirming daratumumab-based quadruplet induction regimens (D-VRd, D-KRd, D-VCD, D-PAD) as preferred first-line approach for transplant-eligible patients, followed by bortezomib-intensified autologous stem cell transplantation and daratumumab-lenalidomide maintenance, as supported by the OPTIMUM/UK Myeloma XI trial [10]. Real-world cohort data (2025) confirm improved overall survival with daratumumab-based quadruplets compared with historical regimens, though 5-year survival remains approximately 11%.

Conclusion     

Primary plasma cell leukemia is an aggressive disorder with poor prognosis, sharing features with MM but presenting distinctive clinical, biological, and prognostic characteristics. Careful examination of the blood smear remains a key diagnostic step. The emergence of novel agents - bortezomib, immunomodulators, and more recently daratumumab-based quadruplets - has led to real progress, though outcomes remain markedly poorer than in conventional MM. Further prospective trials integrating anti-BCMA/anti-GPRC5D bispecific antibodies and CAR-T cell therapy are planned specifically for this ultra-high-risk population.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Asmae Kidoun, Chaimae Boujloud: case identification, data collection, manuscript drafting. Imane Douichi, Abdelilah Berhili, Nabiha Trougouty: clinical management, data collection, manuscript revision. Mounia Slaoui, Assya Khermach: hematological analysis and interpretation. Mohammed Bensalah, Rachid Seddik: supervision, critical revision, final approval. All authors read and approved the final manuscript.

Acknowledgements     

Asmae Kidoun, Chaimae Boujloud: case identification, data collection, manuscript drafting. Imane Douichi, Abdelilah Berhili, Nabiha Trougouty: clinical management, data collection, manuscript revision. Mounia Slaoui, Assya Khermach: hematological analysis and interpretation. Mohammed Bensalah, Rachid Seddik: supervision, critical revision, final approval. All authors read and approved the final manuscript.

Figures     

Figure 1: electrophoretic profile showing hypoalbuminemia associated with hyperalpha-1 globulinemia and hypogammaglobulinemia, to be correlated with clinical and biological data
Figure 2: serum immunofixation (left) shows a clear, very high-intensity band isolated to the lambda level, with no corresponding bands at IgG, IgA, IgM, IgD, or IgE; urine immunofixation (right) shows a lambda-type free light chain
Figure 3: May—Grünwald—Giemsa-stained peripheral blood smear showing 19% plasma cells (3,760/mm³), including dystrophic plasma cells and plasmoblasts
Figure 4: May—Grünwald—Giemsa-stained bone marrow smear (magnification x1000) revealing bone marrow invasion by dystrophic plasma cells (87% infiltration), including plasmoblasts and pro-plasmocytes

References