Case 75 – Summary!
Thank you for all of the contributions with Case 75, where we encountered a 43 year old who presented with back pain and circulating plasma cells in his peripheral blood.
In summary we established that this young man had a mild leucocytosis (WCC 23) with marked anaemia and thrombocytopenia (Hb 73, Plts 45). He had associated acute kidney injury and hypercalcaemia. He had an IgA paraprotein (18g/l) with a discrepantly high serum free light chain ratio of 6543. B2 microglobulin 8.7 and hypoalbuminaemia 28.
He had >2 x 109/L of circulating cells with the following immunophenotype (CD20+, CD38+, CD138+, CD56-) confirming the diagnosis of primary plasma cell leukaemia (he had no previous history of myeloma). He had a high tumour burden in his bone marrow with 66% plasma cells. He had a normal karyotype (even though he has normal cytogenetics he has high risk disease and this would not influence our future management). Within our case we did not focus upon bone imaging.
He received treated with a bortezomib-based regime (velcade, thalidomide and dexamethasone). We would aim to consolidate with a melphalan autologous stem cell transplant and discussed with transplant team regarding the role of an allogenic stem cell transplant.
Plasma cell leukaemia
Primary plasma cell leukaemia is a rare, aggressive plasma cell dyscrasia with a poor prognosis. It is defined by the presence of >2×109/L peripheral blood plasma cells or plasmacytosis accounting for >20% of the differential white cell count, and does not arise from pre-existing myeloma.
Primary plasma cell leukaemia has different clinical, laboratory and biological in comparison to myeloma as listed below:
Younger age at presentation
More advanced disease at presentation (>80% with Stage III disease)
More extensive bone disease
Extramedullary involvement is more common e.g hepatosplenomegaly, lymphadenopathy, plasmacytomas, leptomeningeal disease
Leucocytosis and more marked cytopenias in comparison to multiple myeloma
Higher incidence and severity of renal impairment, hypercalcaemia and LDH/B2 microglobulin
Blood film: commonly leucoerythroblastic along with circulating plasma cells
Bone marrow biopsy: typically high tumour burden
Immunophenotype: CD38+, CD138+. In comparison to multiple myeloma more likely to be:
• CD56- (likely due to higher incidence t(11;14)
• CD117-, HLA-DR-
• CD20+, CD23+
There are usually multiple genetic abnormalities (and often high risk abnormalities) present at diagnosis as opposed to the gradual acquisition of genetic events that occur in end stage myeloma / secondary plasma cell leukaemia. In primary plasma cell leukaemia the genetic aberrations present result in bone marrow microenvironment-independent tumour growth.
Common cytogenetic abnormalities:
• IgH translocations – most commonly t(11:14), t(14:14), t(14:16)
• Del(17p), del (13q), del(1p21), ampl(1q21)
Given the rarity of this condition there is a paucity of data on treatment regimens and participation in a clinical trial, if available, is recommended. However, bortezomib are known to be associated with better outcomes as it more rapidly reduces tumour load and has been found to overcome some adverse cytogenetics including del(17p) and t(4;14).
There is no evidence to guide a particular bortezomib-based regimen and various regimens are used internationally reflecting different countries historic use and also access to first line immunomodulating or novel agents.
Regimens commonly in used for first line therapy include:
• VTD – bortezomib, thalidomide and dexamethasone
• RVD – lenalidomide, bortezomib and dexamethasone
• PAD – bortezomib, doxorubicin and dexamethasone
• VCD – cyclophosphamide, bortezomib, dexamethasone
Commonly in the UK VTD is used as first line therapy. Whereas thalidomide is often replaced by lenalidomide in this regime in Europe where Lenalidomide is available as first line. Lenalidomide has been shown to be more efficacious than Thalidomide in multiple myeloma.
• Blood transfusions
• Antimicrobial prophylaxis
• Prophylaxis against tumour lysis syndrome should be instituted
• Consideration for radiotherapy for problematic plasmacytomas
Autologous Haematopoietic Stem Cell Transplant:
Autologous stem cell transplant improves both progression-free survival and overall survival and should be encouraged if the patient is considered fit to undergo the procedure providing they have achieved at least a partial response. Conditioning regimens are melphalan-based. Trials have discussed the potential role for consolidative treatment (e.g further cycles of VTD but this is not available within the UK) or maintenance therapy (e.g lenalidomide)
Allogenic Haematopoietic Stem Cell Transplant
Unfortunately the prognosis following autologous stem cell transplant remains poor and allogenic stem cell transplants are associated with reduced risk of relapse in comparison (albeit with higher rates of TRM). This could therefore be considered in young, fit individuals following discussion within the MDT. However, there remains to be limited data in this area and ideally this should be performed as part of a clinical trial.
Niels et al. How I treat plasma cell leukaemia. Blood. 120(12), 2376-2389. 2012.