Guido J Tricot

Cytogenetics and Chromosomal Abnormalities in Multiple Myeloma-A Review

Multiple myeloma constitutes about 1% of all malignancies. It has complex cytogenetic and heterogeneous clinical presentations. Recent advances in molecular diagnostic methods have shed light into the chromosomal and molecular changes underlying the pathogenesis of plasma cell dyscrasias, such as Monoclonal Gammopathy of Unknown Significance (MGUS), Smoldering Myeloma (SMM), Multiple Myeloma (MM), and plasma cell leukemia. It is now well established that majority of hypodiploid and hypotetraploid karyotypes, otherwise known as non-hypodiploid karyotypes, harbor chromosomal changes that are considered high risk and have an aggressive disease course. The hyperdiploid category consists of trisomies of uneven chromosomes, and majority of the patients have a good prognosis, although a minority of patients have aggressive disease with up-regulation of proliferative genes. Risk stratification with gene expressions profiling and aCGH studies have helped classify patients into high risk, intermediate risk and good risk categories which are helpful in guiding therapy. While t(4;14) and del(17p) are considered to be the most deleterious cytogenetic abnormalities, del(13) by FISH analysis is considered an intermediate risk and t(11;14) is considered as a good risk marker. The worst outcomes are observed in the high risk category, and even the most intensivexa0 treatments cannot fully overcome the negative impact of genetic findings. Although some novel agents are showing promise in changing the outcomes of t(4;14), del(17p) remains a challenging disease. While many targeted therapies are under development, more work needs to be done in establishing and integrating routine testing of these cytogenetic markers into clinical practice to individualize treatment although within specific genetic subgroups there remains a high degree of variability in outcome determined by other factors, mainly the extent of the disease.

Potential pitfalls of serum free light chain analysis to assess treatment response for multiple myeloma

Response to treatment in patients with a plasma cell disorder is typically measured by evaluating the bone marrow and myeloma markers, including monoclonal protein spike and immunofixation (IFE) in blood and urine, and serum free light chains (sFLCs). Stringent complete response criteria for Multiple Myeloma (MM) patients require a normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. We performed a retrospective chart review to further evaluate these criteria. A total of 142 patient charts were analysed. Of these, 17 patients were found to have an abnormal sFLC ratio, but no other evidence of disease, including normal flow cytometry and normal fluorescence in situ hybridization (FISH) analysis on highly selected plasma cells. In all patients, the abnormal sFLC ratio was caused by abnormalities in the serum kappa light chains. These results suggest that current definitions may need to be revised to take aberrancies related to abnormal immune recovery into account.

Bloodless tandem autologous transplant in Jehovah’s Witness patients

Tandem autologous transplants are generally the preferred therapy for newly diagnosed intermediate- and high-risk myeloma patients. More Jehovah’s Witnesses (JW) are receiving single autologous peripheral blood stem cell transplants (PBSCTs). However, tandem autologous transplants have not been reported in JW patients. We performed a retrospective study of 54 patients, including four JW patients who received tandem autologous transplants between August 2000 and January 2017 and the last 50 consecutive tandem autologous transplants performed between August 2014 and August 2016. The bleeding complications, number, and cost of transfusions of blood products were compared. The median number of CD34 cells infused in non-JW patients was 8.16 million cells/kg versus 9.44 million cells/kg in JW patients. During the first 30 days, one JW experienced Grade III pulmonary hemorrhage, while none of the non-JW patients had a Grade III or higher bleeding problem. After tandem autologous transplants, complete remission was achieved in 88% of non-JW, compared with 75% in JW patients. In the first 30 days post-transplant, median platelet and packed red blood cell (PRBC) transfusions in non-JW patients was 2 (range: 0–40) and 1 (range: 0–11), respectively. Total cost of PRBC and platelet transfusions for the 50 non-JW was

Nek2 Stabilization By Usp7 Leads to Activation of NF-Kb in Multiple Myeloma

214,664 (average

Does Your Smoldering Myeloma Patient Need Treatment? Evidence Based Recommendations

2147/transplant). Tandem autologous transplants can thus be performed safely without a single blood transfusion.