Secondary Plasma Cell Leukemia Research Articles

Single-center experience of patients with plasma cell leukemia in the era of new therapeutics.

Plasma cell leukemia (PCL) can occur de novo as primary PCL (pPCL), or in patients with prior diagnosis of multiple myeloma (MM) as secondary PCL (sPCL). In 2021, the diagnostic criteria have been revised, establishing a new cut-off of ≥ 5 % plasma cells in the peripheral blood. Lacking specific clinical trials, PCL is treated similarly to MM, however outcome for patients with PCL remains poor. Here, we report outcomes for patients with pPCL and sPCL in the era of novel agents. We performed a retrospective analysis and identified 19 patients (11 pPCL, 8 sPCL) who have been treated for PCL between 2010 and 2022 at University Hospital Essen. Patients with pPCL had a median overall survival (OS) of 37.8 months (95% CI: [15.4; 52.3] months) from diagnosis, with a median time to next treatment (TTNT) of 18.4 [2.0; 22.9] months. All patients were treated with a proteasome- inhibitor (PI)-based induction therapy and the majority was consolidated with an autologous stem cell transplantation (SCT). Five of these patients received a tandem transplantation. Patients with sPCL had a median OS of only 1.5 months after diagnosis of PCL. Only one patient achieved a remission with daratumumab and subsequent allogenic SCT. With our study, we add evidence for a PI-based induction therapy followed by a consolidating autologous stem cell transplantation for patients with pPCL and give further evidence that a tandem transplant concept might be beneficial. The diagnosis of sPCL remains devasting and needs new therapeutic approaches.

Secondary plasma cell leukaemia (PCL) with plasmablastic morphology.

A 71-year-old female with relapsed IgA lambda myeloma developed progressive cytopenia. The peripheral blood film showed 5% blastoid cells. Flow cytometry analysis was indicative of plasma cells. The bone marrow smear was packed with plasmablasts. Target CD138-cell FISH and molecular karyotyping identified a complex genome. NGS identified high-risk mutations. Bone marrow histology confirmed myeloma with no evidence of acute leukaemia. The patient was diagnosed with plasmablastic progression of myeloma and secondary PCL. Secondary PCL patients have a poor prognosis. It is essential to recognize this subtype and explore a novel treatment approach.

Primary or Secondary Plasma Cell Leukemia: Dismal Outcome Despite Modern Treatments

BACKGROUND Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia, associated with short survival. This disease is usually divided into primary PCL (pPCL), when occurring de novo, or secondary PCL (sPCL), when a patient previously diagnosed with multiple myeloma (MM) undergoes leukemic transformation. Because of the very low incidence of PCL, only a few cohorts have been reported and thus, information on this disease is scarce. The goal of this study was to better understand PCL, particularly in regard to the characteristics of MM before leukemic transformation and the outcomes following modern treatments in both pPCL and sPCL. METHODS We performed a retrospective, multicenter study of patients diagnosed with PCL between January 2005 and December 2020 in eight institutions in the Province of Québec, Canada. Patients were identified through digital medical records. The 2013 International Myeloma Working Group (IMWG) diagnostic criteria for PCL (circulating plasma cells ≥ 20% and/or ≥ 2 x 10 9/L) were used to determine eligibility. Patients were excluded if they received treatment for another malignancy after the diagnosis of PCL. RESULTS We identified 99 eligible PCL patients, of whom 33 were pPCL and 66 were sPCL. Among significant clinical characteristics, both pPCL and sPCL patients showed a high frequency of thrombocytopenia, splenomegaly, and light chain isotype (Table I). At MM diagnosis, patients who eventually progressed to sPCL were much younger (median 61.8 years) than a typical MM cohort and many of them already demonstrated markers of poor prognosis, including elevated lactate dehydrogenase (LDH), elevated ß 2-microglobulin and complex cytogenetics (Table I). The median time between initial MM diagnosis and leukemic progression was 27.3 months (IQR, 12.7 - 41.6). The median number of lines of treatment prior to transformation was 2 (range 1 - 7). Overall, autologous stem cell transplant (ASCT; n = 28) or tandem ASCT-allogeneic stem cell transplant (ASCT-alloSCT; n = 4) did not result in longer time to PCL progression when compared to those who received chemotherapy alone (31.6 vs 22.9 months, p = 0.164). Median overall survival (OS) for pPCL and sPCL were respectively 18.3 months (95% CI, 0.0 - 39.0) and 1.2 months (95% CI, 0.9 - 1.5) (p < 0.001). When considering survival from MM diagnosis to death, the median OS for sPCL was 30.2 months (95% CI, 24.1 - 36.2). Patients with pPCL who underwent ASCT or tandem ASCT-alloSCT had a significantly longer OS than patients treated with chemotherapy alone (HR 0.27, 95% CI 0.11 - 0.64, p = 0.003). The impact of stem cell transplant on sPCL survival could not be assessed, as only one of 66 sPCL patients received this type of treatment. The median number of lines of treatment was 2 (range 1 - 9) for pPCL and 1 (range 0 - 5) for sPCL. Interestingly, patients receiving more recent regimens (2013-2020) did not have a better OS than patients receiving earlier treatments (2005-2012) (p = 0.391). When analysed separately, OS for pPCL or sPCL did not improve significantly in the later period (Figure 1). Clinical characteristics independently associated with poor outcomes were sPCL subtype and elevated LDH (respectively, HR 4.9, 95% CI 2.2 - 11.9, p < 0.001 and HR 2.4, 95% CI 1.0 - 5.7, p = 0.049). Although expression of CD19 and/or CD20 was not statistically significant in multivariable analysis, a trend towards improved survival was observed in patients expressing these markers (HR 0.4, 95% CI 0.1 - 1.1, p = 0.062). CONCLUSION This retrospective, multicenter study is one of the largest PCL cohorts reported and we are, to our knowledge, the first to investigate characteristics of MM patients before their transformation into sPCL. Although this subgroup is often described as a late-stage complication of heavily pretreated MM, our data suggest that sPCL originates from an already high-risk MM population rather than being the result of long-term selection of an aggressive clone. More information is however needed for early identification of MM patients at risk of PCL transformation. Finally, despite the use of newer chemotherapy regimens, we observed no improvement in OS in recent years, highlighting the urgent need for better treatment options for both pPCL and sPCL.

Distinct Genetic Features in Peripheral Blood Represent the Characteristics of Circulating Plasma Cells in Primary Plasma Cell Leukemia

Clonal plasma cells in peripheral blood (PB) are crucial for diagnosing plasma cell neoplasm. The diagnostic criteria for plasma cell leukemia (PCL) have recently been revised to 5% or more circulating plasma cells (CPCs) in PB. Considering that CPCs are an independent worse prognostic factor in multiple myeloma (MM), elucidating how many CPCs are sufficient for distinguishing patients between PCL and other plasma cell neoplasm is important yet uncertain. These CPCs have been recently discussed in MM, characterized by more immature phenotype, clonogenic potential, and high expression of cancer stem cell (CTC) markers. Though the exact mechanism of peripheral circulation still needs further studies, MM CTCs are considered subclones of bone marrow (BM) plasma cells. On the other hand, previous studies regarding PB plasma cells in primary PCL (pPCL) have been mainly focused on similar characteristics to BM plasma cells. Considering significant prognostic differences based on CPCs, PB from PCL patients should have distinct features. Previous studies on PCL revealed that high genetic heterogeneity and accumulation of diverse high-risk genetic abnormalities eventually led to the disease. Therefore, we aimed to investigate the genetic profile of CPCs in PCL to exhibit proper evidence for diagnostic criteria and improve the current practices. We retrospectively identified patients diagnosed with PCL from 2015 to 2017 at Seoul National University Hospital. Our study population included 4 pPCL and 2 secondary PCL (sPCL) patients. We retrospectively collected patients' clinical information and laboratory test results and performed targeted sequencing using the NGS panel of 647 genes related to hematologic malignancies. In all analyzed samples, 51 in PB and 40 variants in BM were detected in pPCL. The median number of variants in pPCL patients was 11 per patient (range 5-25) in PB and 10 per patient (range 3-17) in BM. When comparing variant allele frequency (VAF) between the paired samples, there was a moderate correlation (R=0.44, P<0.05). Similarly, a moderate correlation was observed in both pPCL (R=0.41, P<0.05) and sPCL (R=0.47, P<0.05) groups. When comparing paired variants between PB and BM, 38 were commonly detected in both samples in pPCL patients. Fifteen variants were identified in only one of the two samples, 12 in PB and 3 in BM. Most variants showed a heterogeneous distribution of genes. We checked the paired samples using an Integrative genomics viewer. As a result, twelve pPCL and thirteen sPCL variants were identified in the paired samples. These variants were initially excluded in the filtering process because of low VAF. Consequently, three unique variants were identified in each pPCL and sPCL group, which were considered truly unique. In pPCL patients, MED12, VPS13B variant from PB, and ZMYM3 variant from BM were identified in one of the paired samples. In sPCL patients, unique variants were identified in ARID1A, FANCE, and TP53. In addition, we determined that PB VAF is higher than BM VAF in shared variants of pPCL patients. Conversely, BM VAF tended to be higher than PB VAF in sPCL. However, plasma cell% was generally higher in BM than PB, regardless of pPCL or sPCL. Therefore, the differences in the percentage of plasma cells between PB and BM samples cannot explain the unique variants detected in only one of the paired samples. pPCL is an aggressive disease characterized by a markedly high diversity of heterogeneous mutation distribution and high mutational burden. The clinical outcomes of pPCL are still poor in the novel agent era. There is an urgent need to improve the current diagnosis and treatment strategy. As shown in this study, CPCs in pPCL are not simply part of the malignant plasma cells shed from the BM but have characteristics distinct from them. In this study, we exhibited that PB variants had higher VAF than BM variants, and some unique variants were identified only in the PB samples. Conversely, in sPCL, more diverse variants were detected mainly in BM samples, and VAF was also higher in BM than PB. Considering unique variants detected in PB and the high genetic heterogeneity of the disease, PB should be included in the diagnosis of PCL to determine the exact genetic profile.

Primary and Secondary Plasma Cell Leukemia Risk Stratification By Circulating Plasma Cells

Plasma cell leukemia (PCL) is a rare plasma cell dyscrasia associated with poor outcomes. PCL can present de novo as primary PCL (pPCL) or from preceding multiple myeloma as secondary PCL (sPCL). The International Myeloma Working Group (IMWG) in 2021 updated the diagnostic criteria for pPCL using circulating plasma cells (CPC) to ≥5% instead of ≥20% as both carry similar survival. In this single center retrospective analysis, we compared clinical features and overall survival (OS) for 104 patients: with pPCL ≥5% CPC ( N = 35), sPCL 5-19% CPC (sPCL-A) ( N = 11), sPCL ≥20% CPC (sPCL-B) ( N = 38), and spillover group 1-4% CPC regardless of newly diagnosed or secondary status ( N = 20). Mean ages were 57 - 59 years old for all groups (range: 25 - 84) with no difference in age between groups ( p = 0.90). There was a slight predominance of females (54.8%) over males and blacks (53.9%) over non-blacks. More patients with pPCL were black (65.7%) compared to sPCL and spillover groups, although this difference was not statistically significant ( p = 0.35). pPCL patients presented with the highest mean WBC at diagnosis (23.4 x10 9/L) compared to sPCL-A (5.5 x10 9/L), sPCL-B (12.2 x10 9/L), and spillover (7.2 x10 9/L) groups ( p <0.001). Patients in all groups were anemic (hemoglobin 7.8 - 9.3 g/dL), thrombocytopenic (platelets 60.2 - 101.2 x 10 9/L), and had abnormal renal function (creatinine 1.4 - 2.7 mg/dL), elevated LDH (918.7 - 1515.5 units/L, highest in sPCL-A), and elevated uric acid levels (5.9 - 8.2 mg/dL). sPCL patients and spillover group had more lytic lesions on skeletal survey ( p = 0.009) and positron emission tomography (PET) ( p = 0.02) compared to patients with pPCL. sPCL-A patients had higher incidences of lymphadenopathy ( N = 5/11, 62.5%, p = 0.02) and central nervous system invasion ( N = 4/11, 36.4%, p = 0.02) compared to other groups. There was no difference in incidence of extramedullary disease ( p = 0.29) between groups. Over 90% of patients with PCL had high-risk cytogenetics with 63% carrying a complex karyotype. Hypodiploidy was seen more often in patients with pPCL and sPCL-B compared to sPCL-A and spillover ( p = 0.005). There was no difference between groups in incidence of deletion 17p ( p = 0.53). All patients benefited in terms of OS from daratumumab (HR 0.44, 95% CI 0.25 - 0.76; p = 0.004), IMiDs (HR 0.13, 95% CI 0.08 - 0.23; p <0.001), PIs (HR 0.43, 95% CI 0.25 - 0.75; p = 0.003), chemotherapy (HR 0.56, 95% CI 0.32 - 0.98; p = 0.04), and autologous hematopoietic stem cell transplantation (HR 0.33, 95% CI 0.16 - 0.71; p = 0.004). DVT-PACE type regimens (dexamethasone-bortezomib-thalidomide-cisplatin-doxorubicin-cyclophosphamide-etoposide) are used for pPCL and may be less effective in sPCL and spillover patients who have been heavily pretreated. We noted no benefit in OS for all patients including pPCL, sPCL-A, sPCL-B, and spillover groups who received DVT-PACE (HR 0.97, 95% CI 0.62 - 1.50, p = 0.88). The lack of OS benefit in pPCL patients receiving DVT-PACE persisted on multivariate analysis when adjusting for PCL group alone (HR 0.79, 95% CI 0.50 -1.26; p = 0.33) and PCL group, age, platelet count, and presence of high-risk cytogenetics (HR 1.11, 95% CI 0.63 - 1.94; p = 0.72). After median follow-up of 6.70 months, median OS was 7.14 months for the entire cohort with 92.3% ( N = 96) deceased. On univariate analysis, male sex, age >58 years old, high-risk cytogenetics, LDH >604 units/L, creatinine >1.40 mg/dL, hemoglobin <8.3 g/dL, platelets <53.5 x10 9/L, lytic lesions on skeletal survey and on PET, extramedullary disease on PET, and plasmacytoma were associated with inferior median OS (Table 1). pPCL had higher median OS (13.1 months) compared to sPCL-A (3.1 months, p = 0.03) and sPCL-B (3.5 months, p = 0.003) (Figure 1). There was no statistically significant difference in median OS between pPCL (13.1 months) and spillover patients (10 months) ( p = 0.48) as well as sPCL-A (3.1 months) and sPCL-B (3.5 months) ( p = 0.80). Although the spillover group was associated with a trend towards better OS compared to sPCL-A and sPCL-B groups, this was not statistically significant, which may be due to low N which is a limitation of the study. Further research is required to better understand the clinical features, treatment responses, and outcomes of pPCL, sPCL, and spillover group (1-4% CPC).

Plasma cell leukemia in a 34-year-old male: rare scenario case report

Introduction: Plasma cell leukaemia is an uncommon plasma cell dyscrasia with a very poor prognosis. It is more common among males and usually presents between 55 and 65 years of age. Case presentation: A 34-year-old male presented to Al-Assad hospital with unremitting back pain. He was given analgesics but his pain was unresponsive to treatment, and due to the COVID-19 pandemic, he refused a computed tomography scan in the hospital. Later that year, he presented again with weight loss, nausea, abdominal pain, melena, and ascites. He was pale with a moderately distended abdomen. Laboratory tests revealed anaemia, thrombocytopenia, hypercalcemia, increased total proteins, and elevated lactate dehydrogenase. Flow cytometry findings of the bone marrow aspirate showed the presence of 30% of plasma cells, positive for CD38, CD56, and kappa light chains. He was diagnosed with secondary plasma cell leukaemia and started on chemotherapy; however, he could not continue his treatment due to myeloid inhibition. He passed away 5 months later. Clinical discussion: Multiple myeloma was not suspected in the patient due to his young age. The diagnosis was delayed even further due to the COVID-19 pandemic. His multiple myeloma progressed into secondary plasma cell leukaemia and had uncommon features like small intestinal polyps. Even though there has been groundbreaking advancements in chemotherapy, plasma cell leukaemia still possesses a fatal prognosis. Conclusion: This report showcases a rare age presentation with unique manifestations of secondary plasma cell leukaemia. Multiple myeloma should be a differential diagnosis for cases with unexplained back pain despite an unclassical age.

Clinical and cytogenetic characteristics of primary and secondary plasma cell leukemia under the new IMWG definition criteria: a retrospective study

ABSTRACTBackgroundPlasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, exhibiting a more unfavorable prognosis than multiple myeloma. PCL is classified into pPCL and sPCL. Recently, the IMWG has recommended new PCL definition criteria, which require the presence of ≥5% circulating plasma cells in peripheral blood smears. Due to its low incidence, research on pPCL and sPCL is limited.MethodsWe conducted a retrospective study and analyzed clinical and cytogenetic data of pPCL and sPCL patients. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan-Meier method, and survival distributions were compared using the log-rank test.ResultsThis is a small cohort comprising 23 pPCL and 9 sPCL patients. Notably, sPCL patients showed a higher incidence of extramedullary infiltration and a higher percentage of bone marrow plasma cells (p = 0.015 and 0.025, respectively). Although no significant difference was found between the two groups in OS and PFS, a trend emerged suggesting a superior survival outcome for pPCL patients, with a higher cumulative 1-year PFS rate (38.3% vs. 13.3%) and a lower early mortality rate (mortality rate at 3 months: 15% vs. 33%). We also suggested that pPCL patients carrying t(11;14) may have a longer median survival time than individuals with other cytogenetic abnormalities, but this was not confirmed due to the small sample size.ConclusionOur study revealed clinical and cytogenetic features of pPCL and sPCL patients according to the new diagnostic criteria. The findings suggested a generally better prognosis for pPCL than sPCL and the likelihood of t(11;14) translocation acting as a favorable prognostic factor in pPCL. It is important to note that our study had a limited sample size, which may lead to bias. We hope well-designed studies can be conducted to provide more results.

BCLXL PROTAC degrader DT2216 targets secondary plasma cell leukemia addicted to BCLXL for survival.

Secondary plasma cell leukemia (sPCL) is a rare form of aggressive plasma cell malignancy arising mostly at end-stage refractory multiple myeloma and consequently presenting limited therapeutic options. We analyzed 13 sPCL for their sensitivity to BH3 mimetics targeting either BCL2 (venetoclax) or BCLXL (A1155463) and showed that 3 sPCL were efficiently killed by venetoclax and 3 sPCL by A1155463. Accordingly, BH3 profiling of 2 sPCL sensitive to BCLXL inhibition confirmed their high BCLXL primed profile. While targeting BCLXL using BH3 mimetics induces platelets on-target drug toxicity, the recent development of DT2216, a clinical-stage BCLXL proteolysis targeting chimera PROTAC compound, provides an alternative strategy to target BCLXL. Indeed, DT2216 specifically degrades BCLXL via VHL E3 ligase, without inducing thrombocytopenia. We demonstrated in human myeloma cell lines and sPCL that sensitivity to DT2216 strongly correlated with the sensitivity to A1155463. Interestingly, we showed that low doses of DT2216 (nM range) were sufficient to specifically degrade BCLXL after 48 hours of treatment, consistent with VHL expression, in all cell lines but irrespectively to DT2216 sensitivity. In myeloma cells, DT2216 induced apoptotic cell death and triggered BAX and BAK activation. In conclusion, our study demonstrated that patients with sPCL addicted to BCLXL, a small but a very challenging group, could potentially receive therapeutic benefit from DT2216. Clinical trials of DT2216 in this subset of sPCL patients are warranted.

Plasma cell leukemia: A multicenter retrospective study of 150 patients.

8014 Background: Despite the use of novel induction regimens, stem cell transplantation (SCT), and maintenance therapy, plasma cell leukemia (PCL) remains a challenging disease with a dismal prognosis. Currently, there is no agreed standard of care management for PCL. We conducted a multicenter retrospective analysis of the clinical presentation, treatment, and outcomes of 150 patients with PCL. Methods: Data of patients diagnosed with pPCL or sPCL between 01/2010 and 01/2021 were entered into a study-specific REDCap database from 7 different U.S. academic sites. PCL was defined as ≥ 5% circulating plasma cells. Clinical data included baseline patient characteristics, clinical presentation, treatment, therapeutic response, and survival outcomes. Overall survival (OS) curves were plotted using the Kaplan-Meier method. Cox proportional hazards regression tested associations between patient characteristics and OS, generating hazard ratios (HR) and 95% confidence intervals (CI), adjusted for PCL type (primary or secondary) and SCT. Results: The analytical cohort included 93 pPCL and 57 sPCL patients. Median age at diagnosis was 60 years. High-risk cytogenetics were found in 56.7% of the patients where it was documented. Of the 79 patients with a documented induction regimen, 58.2% received a proteasome inhibitor triplet, 22.8% received a VTD-Pace like conventional chemotherapy, and 3% received a daratumumab quadruplet regimen. SCT (autologous or allogeneic) was done in 56.1% of the patients. The median OS for all patients, those with pPCL, and those with sPCL was 20.3, 36.6, and 3.2 months, respectively. Secondary PCL was associated with worse survival outcomes compared with pPCL (HR, 2.46; 95% CI, 1.51-3.98; p<0.001) (Table). Median OS was better in patients treated with a proteasome inhibitor triplet regimen vs VTD PACE-like combination (28.2 versus 12.6 months). OS was prolonged among patients who underwent any type of SCT compared with those who did not undergo SCT (44.0 versus 5.7 months, p<0.001). Conclusions: This multicenter retrospective study is one of the largest PCL analyses performed to date and reveals the clinical practice patterns of treatment and survival of PCL patients across the U.S. in the novel treatment era. The survival analysis reinforces the poor prognosis in sPCL patients and the continued need for novel treatment approaches in this patient population. While limited by retrospective design, this analysis suggests prolonged survival with transplantation in both pPCL and sPCL. [Table: see text]

Clinical Characteristics and Survival Analysis of Patients with Plasma Cell Leukemia

To investigate the clinical characteristics, therapeutic response and prognosis of patients with plasma cell leukemia (PCL) and improve the understanding of this disease. The clinical manifestations, laboratory tests and treatment response of 27 patients with plasma cell leukemia treated in The Second Hospital of Shanxi Medical University from December 2010 to August 2019 were analyzed retrospectively, and their clinical characteristics were summarized. Kaplan-Meier method was used for survival analysis. There were 18 cases of primary plasma cell leukemia (pPCL) and 9 cases of secondary plasma cell leukemia (sPCL). The male to female ratio was 1.7∶1. The median age was 62 years old. The first manifestations were bone pain, fatigue, fever, splenomegaly and bleeding, and a large number of plasma cell infiltration was observed in the morphological examination of peripheral blood and bone marrow cells. 13 cases were detected by immunotyping and all of them expressed CD38/CD138. 8 cases underwent karyotype analysis, and 3 cases were normal, clonal abnormalities occurred in 5 cases. FISH detection was performed in 12 cases, of which 8 cases were abnormal. In 17 cases of bortezomib based chemotherapy, the ovevall response rate was 52.9%, which was higher than that in the non-bortezomib group, but there was no significant difference between the two groups (P =0.242). The overall median survival time of 27 patients was 6.4 months, the median progression-free survival time was 3.5 months, and the median survival time of patients with pPCL and sPCL was 8.2 months and 2.4 months, respectively, the difference between the two groups was statistically significant (P =0.031). PCL is highly invasive and has diverse clinical manifestations, and is not sensitive to traditional chemotherapy. The median survival time of patients with pPCL is relatively longer than that of patients with sPCL. The chemotherapy regimen based on bortezomib improves the treatment effectiveness and prolongs the survival time of PCL patients.

Plasma cell leukemia: A rare case

Plasma cell leukaemia is an extremely rare haematological malignancy with a poor prognosis. It is defined by the presence in the circulating blood of a number of plasma cells greater than 2 giga/L or greater than 20% of the leukocytes. It presents in two forms: secondary plasma cell leukaemia complicating a known multiple myeloma, and primary plasma cell leukaemia, which is leukaemic in origin. We report the observation of a 52-year-old Moroccan patient who presented with bone pain and general deterioration 3 months before hospitalisation. The haemogram revealed normocytic normochromic anaemia at 8.1 g/dL and hyperleukocytosis. The blood smear showed the presence of 38% of plasma cells. The myelogram confirmed the diagnosis of APL by showing a rich marrow with 63% dystrophic plasma cells. In this case, we emphasise the importance of careful cytological examination of the blood smear.

Clinical Features and Prognosis of Multiple Myeloma Patients with Secondary Primary Malignancies

To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies. The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated. A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the β2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027). The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.

Secondary plasma cell leukemia: Case report

Plasma cell leukemia (PCL) is a rare lymphoproliferative disorder characterized by monoclonal proliferation of plasma cells in marrow and peripheral blood. It is defined by a blood plasma count greater than 2 G/l or a plasma cell count greater than 20% of white blood cells. There are two forms of PCL: primary PCL (primary plasma cell leukemia or PCL-P), which occurs de novo and is diagnosed by blood dissemination, and secondary PCL (secondary plasma cell leukemia or SPL), which is the result of the evolution of multiple myeloma (MM). We report an observation of secondary plasma cell leukemia in a 42-year-old female patient diagnosed at the hematology laboratory of the Mohamed VI University Hospital in Marrakech. The patient was being followed up for chronic end-stage renal failure in whom the etiological assessment of a hypercalcemia of fortuitous discovery revealed MM for which she was put on chemotherapy according to the Velcade-Thalidomide-Dexamethasone protocol with a good evolution after 6 courses. Two and a half years later, the patient presented with anemia and spinal pain. The biological work-up showed a normocytic normochromic anemia at 5.4 g/dl and hypercalcemia at 150 mg/l. The blood smear showed the presence of 22% of circulating plasma cells, the majority of which were dystrophic, in favor of secondary plasma cell leukemia. Patients diagnosed with multiple myeloma who have undergone treatment and have a stable disease should have regular surveillance, hence the interest of the blood smear examination in all multiple myeloma.

Cyclophosphamide etoposide dexamethasone as salvage and bridging therapy in relapsed refractory and extramedullary multiple myeloma.

Patients with relapsed refractory multiple myeloma (RRMM) that are triple-exposed to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies have a poor prognosis. Standard treatment for these patients has not been established. Patients with extramedullary disease or secondary plasma cell leukemia often display high tumor cell proliferation and might therefore be susceptible to chemotherapy. While current regimens are often platinum-based, we present single-center data on 70 patients with RRMM who were treated with cyclophosphamide, etoposide, and dexamethasone (CED) after a median of four lines of therapy. An overall response rate of 52% was achieved after 1-6 cycles, with 23% of patients having a very good partial response. Comparable response rates and survival were observed in patients with extramedullary disease and high-risk cytogenetics. Treatment resulted in non-hematological °III-IV adverse events in 31% of patients. No treatment-related deaths occurred. The median progression-free and overall survival were 6.2 and 10.9months, respectively. 23% of patients were bridged to autologous stem cell transplantation (ASCT) or chimeric antigen receptor (CAR) T cell therapy. In summary, CED is an effective treatment regimen for RRMM cases with a tolerable safety profile and suitable as bridging therapy to CAR T cell treatment and ASCT.

Genomics of Plasma Cell Leukemia.

Plasma cell leukemia (PCL) is a rare and highly aggressive plasma cell dyscrasia characterized by the presence of clonal circulating plasma cells in peripheral blood. PCL accounts for approximately 2-4% of all multiple myeloma (MM) cases. PCL can be classified in primary PCL (pPCL) when it appears de novo and in secondary PCL (sPCL) when it arises from a pre-existing relapsed/refractory MM. Despite the improvement in treatment modalities, the prognosis remains very poor. There is growing evidence that pPCL is a different clinicopathological entity as compared to MM, although the mechanisms underlying its pathogenesis are not fully elucidated. The development of new high-throughput technologies, such as microarrays and new generation sequencing (NGS), has contributed to a better understanding of the peculiar biological and clinical features of this disease. Relevant information is now available on cytogenetic alterations, genetic variants, transcriptome, methylation patterns, and non-coding RNA profiles. Additionally, attempts have been made to integrate genomic alterations with gene expression data. However, given the low frequency of PCL, most of the genetic information comes from retrospective studies with a small number of patients, sometimes leading to inconsistent results.

Atypical presentation of plasma cell leukaemia: A case report

Introduction: Plasma cell leukaemia (PCL) is a rare blood disorder with an aggressive clinical course and dismal diagnosis. PCL is diagnosed based on the presence of an absolute plasma count of more than 2×109/L or 20% plasma cells in the peripheral blood. Initial presentation (primary PCL, pPCL) is 2–4% of myelomas. Secondary PCL is a leukaemic transformation occurring in approximately 1% of previously diagnosed plasma cell myeloma. The incidence of PCL is low, and this case presents a rare opportunity to describe the clinical and pathological characteristics of this disease.

The Cytogenetic Profile of Primary and Secondary Plasma Cell Leukemia: Etiopathogenetic Perspectives, Prognostic Impact and Clinical Relevance to Newly Diagnosed Multiple Myeloma with Differential Circulating Clonal Plasma Cells.

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia that may appear as de-novo leukemia (pPCL) or on the basis of a pre-existing multiple myeloma (MM), called secondary plasma cell leukemia (sPCL). In this prospective study, we have applied a broad panel of FISH probes in 965 newly diagnosed MM (NDMM) and 44 PCL cases of both types to reveal the particular cytogenetic differences among the three plasma cell dyscrasias. In order to evaluate the frequency and patterns of clonal evolution, the same FISH panel was applied both at diagnosis and at the time of first relapse for 81 relapsed MM patients and both at MM diagnosis and during sPCL transformation for the 19 sPCL cases described here. pPCL was characterized by frequent MYC translocations and t(11;14) with a 11q13 breakpoint centered on the MYEOV gene, not commonly seen in MM. sPCL had a higher number of FISH abnormalities and was strongly associated with the presence of del(17p13), either acquired at the initial MM stage or as a newly acquired lesion upon leukemogenesis in the context of the apparent clonal evolution observed in sPCL. In clinical terms, sPCL showed a shorter overall survival than pPCL with either standard or high-risk (t(4;14) and/or t(14;16) and/or del(17p13) and/or ≥3 concomitant aberrations) abnormalities (median 5 months vs. 21 and 11 months respectively, p < 0.001), suggesting a prognostic stratification based on cytogenetic background. These observations proved relevant in the NDMM setting, where higher levels of circulating plasma cells (CPCs) were strongly associated with high-risk cytogenetics (median frequency of CPCs: 0.11% of peripheral blood nucleated cells for high-risk vs. 0.007% for standard-risk NDMM, p < 0.0001). Most importantly, the combined evaluation of CPCs (higher or lower than a cut-off of 0.03%), together with patients’ cytogenetic status, could be used for an improved prognostic stratification of NDMM patients.

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

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.

Descriptive cross-sectional study assessing the clinical and paraclinic profiles of monoclonal gammopathies in an agricultural region of Souss-Massa, Morocco

Introductionpartant de l´observation de manque d´informations sur les gammapathies monoclonales, nous avons fixé comme objectif de dresser les profils épidémiologiques, cliniques et biochimiques des gammapathies monoclonales, au niveau de la région de Souss-Massa au sud du Maroc.Méthodesil s´agit d´une étude rétrospective, où nous avons sélectionné que les dossiers complets. Nous avons exploité les dossiers des patients diagnostiqués avec une gammapathie monoclonale au niveau du centre d´oncologie local, sur une période de plus10 ans.Résultatscent dix-sept (117) patients ont été inclus dans l´étude avec une forte prédominance masculine (65%), un sexe-ratio Homme/Femme de 1,85. De même, la moyenne d´âge de notre population a été de 61,44 (ET 14,54) année. Les diagnostics qui ont été retenus et par ordre de fréquence sont, le myélome multiple 82,0% (n=96), le plasmocytome solitaire 8,5% (n=10), les gammapathies monoclonales de signification indéterminé 2,6% (n=3), trois cas de lymphome 2,5% (n=3), deux cas de leucémies à plasmocytes secondaires 1,7% (n=2), deux cas de maladie de Waldenström 1,7% (n=2) et un cas de leucémie lymphoïde chronique. La répartition selon l´isotype a été comme suit, Les IgG kappa 33,7% (n=28), Les IgG Lambda 21,7% (n=18), Les IgA Kappa 12,0% (n=10), les IgA Lambda 7,2% (n=6) les IgM kappa 3,6% (n=3) et les IgD Lambda 2,4% (n=2). Le pic biclonal a été retrouvé dans deux cas avec un pourcentage de 2,4%.Conclusionun retard de diagnostic des patients a été remarqué par rapport aux études internationales du à la non disponibilité des électrophorèses dans les structures des soins.

Successful treatment with current pomalidomide-containing agents for secondary plasma cell leukemia

Successful treatment with current pomalidomide-containing agents for secondary plasma cell leukemia