scholarly journals Primary plasma cell leukaemia in a 39-year-old man

2020 ◽  
Vol 13 (7) ◽  
pp. e235543
Author(s):  
Ganesh Kasinathan
Keyword(s):  
Plasma Cell ◽  
Plasma Cells ◽  
Autologous Stem Cell Transplant ◽  
Blood Film ◽  
Cell Leukaemia ◽  
High Dose ◽  
Cell Transplant ◽  
Plasma Cell Leukaemia ◽  
History Of ◽  
High Dose Melphalan

Plasma cell leukaemia (PCL) is an aggressive haematological malignancy which is classified into primary (pPCL) and secondary PCL. A 39-year-old Indian man presented to the Department of Hematology with a 2-week history of fever and lethargy. Clinically, he was pale and febrile. Haemogram revealed bicytopenia with leucocytosis. The peripheral blood film portrayed rouleax formation with 45% of circulating plasma cells. Serum protein electrophoresis and immunofixation revealed IgG lambda paraproteinaemia of 48 g/L. Bone marrow aspirate, flow cytometry and trephine were consistent with IgG lambda pPCL. He was treated with six cycles of bortezomib, thalidomide and dexamethasone combination chemotherapy followed by high-dose melphalan conditioning and autologous stem cell transplant. Currently, he is in complete remission for the past 18 months and is on oral lenalidomide maintenance therapy. Prognosis is often dismal in pPCL with the median overall survival below 1 year if treatment is delayed.

Plasma cell leukaemia with t(11;14) not responsive to venetoclax

2021 ◽  
Vol 14 (1) ◽  
pp. e238641
Author(s):  
Mohammed Isaac Abu Zaanona ◽  
Priyank Patel
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
In Situ Hybridisation ◽  
Haematopoietic Stem Cell ◽  
Successful Outcome ◽  
Cell Leukaemia ◽  
Plasma Cell Leukaemia ◽  
History Of ◽  
Early Phase Clinical Trials

A 70-year-old man with medical history of IgG kappa multiple myeloma, initially diagnosed in 2017, underwent induction therapy with carfilzomib, lenalidomide and dexamethasone followed by autologous haematopoietic stem cell transplantation. Nine months following transplant, disease relapsed in the form of plasma cell leukaemia. Fluorescent in situ hybridisation of malignant plasma cells revealed t(11;14). A combination therapy including venetoclax was used based on efficacy data for Bcl-2 inhibitor venetoclax from available early-phase clinical trials in patients with relapsed multiple myeloma with t(11;14) and other published case studies. Unfortunately, the disease was primary refractory, and after further ineffective therapies, the patient did not have a successful outcome.

2 Translocations, t(11;14) and t(l;6), in a Patient with Plasma Cell Leukaemia and 2 Populations of Plasma Cells

2009 ◽  
Vol 24 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Gösta Gahrton ◽  
Lore Zech ◽  
Kenneth Nillsson ◽  
Berit Lönnqvist ◽  
Anders Carlström
Keyword(s):  
Plasma Cell ◽  
Plasma Cells ◽  
Cell Leukaemia ◽  
Plasma Cell Leukaemia

scholarly journals A Phase 2 Multi-Center, Open Label Study of Isatuximab Added to Standard Cybord Induction and Lenalidomide Maintenance Treatments in Newly Diagnosed, Transplant Eligible Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4767-4767
Author(s):  
Rami Kotb ◽  
Engin Gul ◽  
Donna E. Reece
Keyword(s):  
Stem Cell ◽  
Sample Size ◽  
Research Funding ◽  
Response Rate ◽  
Autologous Stem Cell Transplant ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
High Dose Melphalan

Abstract Background: Despite recent improvements, myeloma is still incurable. There is need to add new therapeutic tools. For young and fit patients, the current standard first-line therapy is a proteasome inhibitor (PI) containing induction, followed by stem cell collection, high dose Melphalan and autologous stem cell transplantation, followed by maintenance lenalidomide therapy in Canada. The anti-CD38 antibodies showed interesting activity in myeloma, and significant synergism with PI and IMiD based regimens. This CMRG-008 trial is designed to explore the benefit of adding Isatuximab to the current Canadian standard of care (CyBorD induction/Autologous SCT/Maintenance Len) in a single arm phase II trial. Design and Methods: Phase II study. Transplant eligible newly diagnosed myeloma patients (TE-NDMM) will receive Isatuximab added to four cycles of standard induction CyBorD chemotherapy (Cyclophosphamide 300 mg/m 2 PO, Bortezomib 1.5 mg/m 2 SC, and Dex 40 mg PO, all given on days 1, 8, 15 and 22 of 28-day cycles; Isatuximab 10 mg/kg IV days 1, 8, 15 and 22 of cycle 1; days 1 and 15 of cycles 2-4). After the completion of the induction treatment, subjects achieving at least stable disease will receive stem cell mobilization, collection of hematopoietic stem cells, high dose melphalan chemotherapy, and autologous stem cell transplantation. Maintenance treatment will start at 100 days (+/- 7 days) after the transplantation date (and to be continued until disease progression). The maintenance treatment will consist of Isatuximab administered in combination with Lenalidomide in 28-day cycles (Lenalidomide: 10 mg daily on days 1-21 of every cycle; Isatuximab: 10 mg/kg IV on days days 1, 8, 15 and 22 of cycle 1; days 1 & 15 of cycles 2-3; then day 1 of each subsequent cycle). The objectives: To evaluate the benefit of adding Isatuximab to CyBorD (induction = Isa + CyBorD) and Lenalidomide (maintenance = Isa + Lenalidomide) in transplant-eligible myeloma patients. Primary Endpoint: To determine the response rate (VGPR or better) defined by IMWG criteria at 100 days (+/- 7 days) after the autologous stem cell transplant (ASCT). Secondary Endpoints: A) To determine the response rate (VGPR or better) after induction treatment (before ASCT), and at 12 months, 24 months and 36 months. B) To evaluate additional efficacy outcomes including progression free survival (PFS), and overall survival (OS), time to response and duration of response. C) To confirm the feasibility, safety and tolerability of adding Isatuximab to CyBorD and to maintenance lenalidomide in transplant-eligible newly diagnosed myeloma patients. D) To determine the feasibility of autologous stem cell collection after Isa + CyBorD induction treatment. The key inclusion criteria are having a TE-NDMM with a measurable disease; adequate performance status; and adequate organ functions. The key exclusion criteria include previous exposure to anti-CD38 therapy, intolerance to CyBorD, adverse cardiac history, pulmonary disease, central nervous system disease, congenital or acquired immune suppression, and other concurrent severe or uncontrolled medical conditions. Statistics and Sample Size: Considering that the response rate (VGPR or better) after CyBorD induction therapy, high dose chemotherapy and autologous SCT is about 70-78%; and assuming a response rate (VGPR or better) to Isa-CyBorD induction and autologous stem cell transplant at 100 +/- 7 days of 88%; a sample size of 65 evaluable subjects will allow estimating the 95% confidence interval with a precision of +/- 7.9%. For the assumed rate and sample size, the lower bound of the confidence interval will be estimated to be larger than 80%. Assuming a 10% drop out rate, a total study size of 72 patients will be considered. This study is expected to open to recruitment in the third quarter of 2021. Clinicaltrials.gov #: NCT04786028. Disclosures Kotb: Janssen: Honoraria; Merck: Honoraria, Research Funding; Amgen: Honoraria; Akcea: Honoraria; Celgene: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria, Research Funding; Takeda: Honoraria; Karyopharm: Current holder of individual stocks in a privately-held company. Reece: BMS: Honoraria, Research Funding; GSK: Honoraria; Karyopharm: Consultancy, Research Funding; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Millennium: Research Funding; Sanofi: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding.

Rapid and Excellent Response to Hyper CVAD, Particularly with Thalidomide, in Plasma Cell Leukaemia and Long Term Remissions Following Allogeneic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4963-4963 ◽  
Author(s):  
Vidhya Murthy ◽  
Anne Mwirigi ◽  
Susan Ward ◽  
Saad M.B. Rassam
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Stem Cell ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Cell Leukaemia ◽  
First Line ◽  
Plasma Cell Disorders ◽  
Plasma Cell Leukaemia

Abstract Abstract 4963 Plasma cell leukemia [PCL] is the most aggressive form of plasma cell neoplasms constituting 2% to 4% of all cases of plasma cell disorders. The presentation may be primary or secondary from an existing multiple myeloma. Approximately 60 to 70% of cases are primary. Immunophenotype of PCL cells differs from the most of other myelomas with more frequent expression of CD20 antigen (50% vs. 17%), and lack CD56 antigen present on the majority of multiple myeloma cells. PCL patients have a higher presenting tumor burden with higher frequencies of anaemia, organomegaly, renal impairment, increased levels of serum lactate dehydrogenase (LDH), β-2 microglobulin and plasma cell proliferative activity. Prognosis of PCL is exceptionally poor with median survival of 6.8 months for patients with primary PCL and 1.3 months for patients with secondary PCL. It responds poorly to conventional myeloma treatment and polychemotherapy approach has yielded some short lived success. Recently, bortezomib has been reported first line in combination with other agents with good initial response. In the UK, bortezomib is not approved as a first line treatment for plasma cell disorders. The Hyper CVAD regimen (fractionated high dose cyclophosphamide and dexamethasone with infusional vincristine and adriamycin) has been developed for acute lymphoblastic leukaemia by the M D Anderson group and has also been shown to be effective in other aggressive B-cell disorders such as mantle cell and Burkitt's lymphoma. There are few single patient anecdotal reports of its efficacy in plasma cell leukaemia. We report three cases of plasma cell leukaemia successfully induced with limited courses of Hyper CVAD chemotherapy and long term remissions achieved with stem cell transplantation. Two men aged 53 and 56 and one woman aged 40 presented with PCL. All were anaemic (median Hb 8.5 g/dl), had impaired renal function, raised beta-2 microglobulin, creatinine, circulating plasma cells and plasmablasts and almost total marrow replacement by plasma cells. Two had IgG kappa paraprotein and one had light chains only. All had weak CD56 expression and two, where tested, were CD38 positive. Cytogenetic analysis was positive in one patient with t(4,14). All received hydration, bisphosphonate and allopurinol preparation before induction with the Hyper CVAD regimen. Two, given Thalidomide as well, achieved morphological complete remission (CR) after one course of therapy with marked reduction of paraprotein and normalisation of renal function. They received one further course of Hyper CVAD before receiving a Melphalan conditioned autlogous stem cell (ASCT) followed by a reduced intensity conditioning (RIC) sibling allogeneiec transplant in one patient. She remains in CR and full donor chimerism 11 months post SCT. The other is being prepared for ASCT to be followed by a RIC voluntary unrelated transplant. The patient with light chain disease achieved partial response (20% plasma cells in the bone marrow) after one course of Hyper CVAD without Thalidomide but a complete response after the second. He was consolidated with a third cycle, followed by a course of mini BEAM and then a RIC sibling allogeneic SCT. He had an early relapse 12 months following his SCT but responded to a course of donor lymphocyte infusion (DLI) and remains in CR 8.5 years from his SCT. Discussion To our knowledge, this is the largest series using this approach in PCL reported in the literature. PCL is a rare but aggressive disease with poor response to conventional therapy and short survival. Hyper CVAD appears to be highly effective in inducing a good response after 1-2 cycles of therapy particularly when combined with thalidomide. It appears that PCL is sensitive to the graft-versus-myeloma effect with long lasting remissions after allogeneic SCT and DLI therapy. Disclosures Rassam: Johnson and Johnson: Research Funding.

Induction Therapy with Bortezomib and Dexamethasone Followed By Autologous Stem Cell Transplantation for Systemic Light Chain Amyloidosis: Our Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5907-5907
Author(s):  
Sandeep Jain ◽  
Luciano J Costa ◽  
Robert K Stuart ◽  
Saurabh Chhabra ◽  
Alice Mims ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cardiac Involvement ◽  
Stem Cell Transplant ◽  
Patient Characteristics ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
High Dose Melphalan

Abstract Introduction: The optimal treatment approach for systemic AL amyloidosis remains unclear. Autologous stem cell transplant (ASCT) is the only modality associated with long term survival, but failure to show survival benefit in randomized clinical trial raises doubts about its efficacy 1, 2. Outcomes after ASCT are better in patients who achieve complete hematologic response after the ASCT3. One report has shown improved outcomes with combining one dose of the proteasome inhibitor bortezomib with high dose melphalan as part of conditioning regimen 4. Preliminary data from a recent study suggest that the outcome of treating AL amyloidosis with two cycles of bortezomib and dexamethasone followed by ASCT was superior to the outcome of the ASCT alone5. We describe our experience with giving 4-6 cycles of bortezomib and dexamethasone induction prior to high dose melphalan and ASCT in patients with systemic AL amyloidosis. Patients and methods: We included all patients who underwent autologous transplant for symptomatic systemic AL amyloidosis at our institution from October 2010 till June 2014. Five patients were included in the analysis and patient characteristics are described in table 1. All patient received 4 -6 cycles of induction with bortezomib and dexamethasone followed by autologous stem cell transplant using high dose melphalan (200 mg/m2). One patient also received six cycles of lenalidomide and dexamethasone prior to bortezomib based induction for lack of response. Hematologic and organ response were assessed using the definitions from the 10th International symposium on Amyloid and Amyloidosis. Overall survival was calculated by Kaplan Meyer’s method using Graphpad Prism 6.0 software. Results: There was no transplant related mortality. After median follow up of 13 months (12-25 months) all patient are alive. Toxicities from the ASCT were mostly cytopenias in the immediate post-transplant period which were managed as per the standard of care. Two patients achieved hematological complete response while one more had very good partial response and other two achieved partial response. Of the four patients with nephrotic range proteinuria, two patients had > 95% reduction in proteinuria, one had > 75% reduction in proteinuria and another patient had > 50% reduction in proteinuria. One patient had Liver involvement with elevated alkaline phosphatase which normalized post-transplant (table 2). The responses were maintained on last follow up and none of the patient had hematological or organ relapses. Discussion: Bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, but its role in induction prior to high dose melphalan/ASCT to help achieve deeper hematological response is unknown. Our experience shows that this combination may be highly efficacious without significant toxicity. Limitations of our study include the small number of patients and absence of any patients with cardiac involvement, which is a worse prognostic marker. We conclude that the bortezomib and dexamethasone induction followed by high dose melphalan/ASCT for AL amyloidosis should be studied in prospective trials. Table 1.Patient Characteristics n=5Age, years 51.2 (44-62)Race (Caucasian)4 (80%)Gender ( female)3 (60%)Cardiac involvement 0 (0)Renal involvement 4 (80%)Serum creatinine ≥ 2.5 0 (0)Organ involvement ≥21 (20%)BM plasma cells > 10%1 (20%)Hgb ≤ 10 g/dl0 (0)LVEF <50%0 (0)Induction therapy Bortezomib/dexamethasone only4 (80%)Lenalidomide/dexamethasone + Bortezomib/dexamethasone1 (20%) Table 2. Outcomes n=5 Baseline After ASCT Hematologic response n=5 M protein 0.772 gm/dl 0.096 gm/dl 2 CR, 1 VGPR, 2 PR Renal response n=4 24 hours proteinuria 3.13 gm 0.432 gm 2 > 95% reduction, 1 >75% reduction, 1 >50 % reduction. Liver response n=1 Alkaline phosphatase 700 IU/L 62 IU/L Disclosures No relevant conflicts of interest to declare.

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