Biochemical profile of multiple myeloma about 50 cases

Multiple myeloma (MM) is a clonal proliferation of plasma cells invading the bone marrow and secreting monoclonal immunoglobulin. In order to study the epidemiological and biological and biochemical characteristics of MM, we carried out a retrospective work on a cohort of 50 cases collected at the Avicenna Military Hospital in Marrakesh, during a period of 5 years (from January 2013 to December 2017). Our study included 32 men (64%) and 18 women (36%), with an average age of 60.6 years, with extremes at 44 and 87 years. The circumstances of discovery were dominated by bone pain and alteration in general condition, which are revealing in more than 65% of cases. Biologically: the sedimentation rate was accelerated in 86% of cases, a monoclonal peak appearance was revealed on serum proteins electrophoresis in 88%of cases, most often located in the γ zone (64%), a predominance of the Ig G isotype (64%), and kappa light chains in 60% of cases, Bence Jones protein (BJP) was found in 7 patients, i.e. 14% of cases, and plasmacytosis over 10% was found on the myelograms in 90 % of cases.

Atypical Nodular Pulmonary Kappa Light-Chain Deposition

We report a case of an incidental positron emission tomography avid right middle lobe lesion which was increasing in size. Due to concerns regarding malignancy, the patient underwent right middle lobectomy. Microscopic examination showed a 12 × 10 × 10 mm poorly circumscribed lesion composed of eosinophilic material. The material labelled strongly for kappa light chains; however, Congo red stain was only weakly positive and without “apple-green” positive birefringence under polarised light. Electron microscopy revealed fibrillar amyloid-like material. The features were those of kappa light-chain deposition.

P0649MAY HIGH CUT-OFF HAEMODIALYSIS STILL BE CONSIDERED BENEFICIAL IN THE TREATMENT OF ACUTE KIDNEY INJURY RELATED TO MULTIPLE MYELOMA?

Background and Aims Almost 20% of the patients with multiple myeloma (MM) associate renal involvement, and 5% need long-term haemodialysis treatment. Both plasmapheresis and high cut-off haemodialysis (HCO-HD) have been used to remove light chains from the blood and minimize the renal damage. In the largest study, plasmapheresis has been shown to be ineffective in the renal recovery. Furthermore, the most important trial, EuLITE II, concluded that HCO-HD did not improve renal recovery and independence from haemodialysis. The hypothesis of this work is that patients with an acute renal failure related to multiple myeloma undergoing early HCO-HD treatment, before being haemodialysis-dependent, may achieve better renal function in short and, perhaps, in long term. Method We have studied five patients with multiple myeloma and acute renal failure who received treatment with HCO-HD in order to remove serum kappa or lambda light chains. The procedure was realized with Filtryzer BK2.1F dialyzer (Palex Medical) with an area of 2.1 m2 at a blood flow of 250 ml/min and a dialysate flow of 500 ml/min, usually changing the dialyzer in the middle of the session. The sessions lasted between 6 and 8 hours, initially on successive days, and alternate days afterwards. Results Between July 2016 and November 2019, five patients with a mean age of 67.8 years (2 women and 3 men) received HCO-HD. Three of them had MM with lambda light chains, and two of them had MM with kappa light chains. The average bone marrow plasmocytosis was 38.6 % (minimum 10% and maximum 90%). Two patients required treatment with haemodialysis for glomerular filtrate (FG) estimated by MDRD-4 formula of 4 and 5 ml/min, respectively. The other three had a GF (MDRD-4) between 19 and 30 ml/min. Initial hematological treatment included bortezomib, dexamethasone, and thalidomide. One patient was switched to carfilzomib. Only two patients underwent renal biopsy, both showing myeloma kidney with intratubular light chain casts. An average of 9.8 sessions has been administered (minimum 5, maximum 19). At the end of the treatment, serum kappa light chains decreased from a mean of 29461 mg/L to 1516.5 mg/L, and serum lambda chains decreased from a mean of 7245 mg/L to 1030.66 mg/L. At the beginning of the treatment the mean GF (MDRD-4) was 17.4 ml/min, 29.6 ml/min at the end of it, and 42.33 ml/min six months later (table 1). Only one patient became dependent of haemodialysis. This patient developed renal failure in context of a second relapse of a very aggressive myeloma. Another patient who presented 47900 mg/L of serum kappa light chains at diagnosis, 90% bone marrow plasmocytosis, and a GF (MDRD-4) of 30 ml/min when started HCO-HD, in the present and few days after 19 sessions has a GF (MDRD) of 43 ml/min. Conclusion An early treatment with HCO-HD, before the patients need renal replacement therapy, may lead to a better renal outcome and independence from haemodialysis at least in the medium term. Largest studies are necessary to confirm this hypothesis.

Waldenstrom-associated anti-MAG paraprotein polyneuropathy with neurogenic tremor

A 71-year-old female patient presented with a 14-year history of slowly progressive distal limb numbness, paraesthesia and reduced vibration perception, ataxic gait and intentional tremor. Examination revealed with a length-dependent sensory neuropathy. Nerve conduction studies showed a chronic sensorimotor inflammatory demyelinating polyneuropathy. Intravenous immunoglobulin treatment (on two occasions) proved ineffective. Serum electrophoresis showed increased monoclonal IgM with kappa light chains. Anti-myelin-associated glycoprotein (MAG) levels were extremely elevated, >70 000 BTU. Bone marrow biopsy revealed 15%–20% small B cells and positive MYD88 mutation, indicative of Waldenstrom macroglobulinaemia. A diagnosis of Waldenstrom-associated anti-MAG paraprotein neuropathy with intentional (neurogenic) tremor was made. Repeat nerve conduction study showed a severe sensory demyelinating neuropathy with no axonal lesion. Treatment with rituximab was given for 1 month with minimal improvement. Repeat anti-MAG levels dropped to 53 670 BTU, with minimal clinical improvement.

Clinical Characteristics and Outcome of Patients with Wild-Type Transthyretin and AL Cardiac Amyloidosis Confirmed By Mass Spectrometry

INTRODUCTION: Cardiac involvement is common in both wild-type transthyretin (wATTR) and AL amyloidosis and these entities can have overlapping clinical features (Banypersad et al, JAHA 2012). Accurate diagnosis is vital given differences in spectrum of disease, management, and prognosis. We examined the presenting clinical features and survival outcome of patients diagnosed with cardiac wATTR and AL amyloidosis confirmed by mass spectrometry. MATERIALS & METHODS: Patients diagnosed between January 2014 and September 2017 with biopsy proven wATTR or AL amyloidosis and cardiac involvement by consensus criteria (Gertz et al, Amyloid 2010) were included. Mass spectrometry testing was performed at the Mayo Clinic Laboratories to confirm amyloid subtype in all cases. Patient records were retrospectively reviewed to identify clinical characteristics as well as details regarding treatment and survival. RESULTS: Forty-three patients were identified (wATTR n=27, AL n=16) with site of biopsy: 41 cardiac (95%); 1 gastric (2%); 1 skin (2%). Two (13%) patients with AL amyloid had coexisting multiple myeloma. Thirty-five (81%) patients were male, with a strong male predominance in wATTR patients (100% vs 50% for AL patients, p=<0.01). Median age at diagnosis was 73 years (range 45-86), with a trend towards older age in wATTR patients (median 75 vs 62 years for AL patients, p=0.09). No difference was seen in presenting NYHA class or levels of troponin and ntProBNP between amyloid subtypes. BNP trended towards higher values in AL patients (median 514 vs 249 ng/L for wATTR, p=0.09). wATTR amyloid patients had lower median presenting left ventricular ejection fraction (43 vs 53%, p=0.05). Two (7%) patients with wATTR amyloid had an M-protein on SPEP compared to 7 (44%) with AL amyloid. Only 2 patients with AL amyloid had M-protein greater than 5 g/L while both wATTR patients had less than 5 g/L. In those with serum free light chain testing available (wATTR n=24, AL n=16), median lambda light chain level was higher in AL patients (176.0 vs 16.9 mg/L for wtATTR, p=<0.01). No difference was seen in kappa light chains (16.5 vs 23.8 mg/L for wATTR, p=0.60), though the only patient with kappa AL amyloid had kappa light chains significantly elevated at 1640 mg/L. The kappa/lambda ratio was abnormal in 15% of wATTR patients (all kappa predominant) compared to 100% in AL amyloid patients (94% lambda predominant) (p=<0.01). The median difference between involved and uninvolved light chain (dFLC) was 22 mg/L for wtATTR patients compared to 249 mg/L for AL patients. In patients with bone marrow biopsy results available (AL n=15, wATTR n=7), bone marrow plasma cell percentage was higher in patients with AL amyloid (median 7% vs 2%, p=0.01). No monoclonal plasma cells were seen on bone marrow in wATTR patients by immunophenotype. Treatment for patients with AL amyloid was: bortezomib, cyclophosphamide, and dexamethasone (VCD) in 11 (69%); VCD followed by melphalan 200 mg/m2 autologous transplantation in 1 (6%); melphalan/dexamethasone in 1 (6%); no treatment in 2 (13%); unknown in 1 (6%). In evaluable patients, hematologic response rate was 54% (complete response n=4, very good partial response n=2, partial response n=1, no response n=6). With a median follow-up of 1.8 years for surviving patients, 1 year overall survival (OS) was 76% for the entire cohort. Patients with AL amyloidosis had significantly poorer 1 year OS (41% vs 92% for wATTR patients, p=<0.01). Patients with NYHA class 3-4 had significantly worse 1 year OS (54% vs 96% for those 1-2, p=<0.01), and this held true for both AL and wATTR patients. In AL patients, revised Mayo stage (Kumar et al, JCO 2012) of III-IV predicted for poor 1 year OS (19% vs 75% for stages I-II, p=0.03), as did not achieving complete response to primary treatment (1 year OS 33% vs 67% for CR patients, p=0.06). DISCUSSION & CONCLUSIONS: Male sex, older age, and lower LVEF were more common in patients with wATTR compared to AL amyloidosis. Higher levels of BNP, larger dFLC with lambda predilection, and higher bone marrow plasma cell percentage were more common in AL amyloid patients. Overall survival was significantly worse for patients with AL amyloidosis, particularly those with high NHYA class, advanced revised Mayo stage, and suboptimal response to primary therapy. These results highlight the importance of accurate amyloid sub-typing in patients with suspected cardiac amyloidosis. Disclosures No relevant conflicts of interest to declare.

HHV8/EBV Coinfection Lymphoproliferative Disorder: Rare Entity with a Favorable Outcome

HHV8/EBV-associated germinotropic lymphoproliferative disorder (GLD) is a challenging diagnosis given its rarity, the particular clinical presentation, and the lack of expression of markers usually used in establishing hematopoietic lineage. We report a new case of HHV8/EBV GLD in an immunocompetent 78-year-old woman. The diagnosis was made in an incidentally discovered lymphadenopathy. Histological examination showed a nodular lymphoid proliferation centered by aggregates of atypical plasmablastic cells admixed with small lymphoid cells. Tumor cells were strongly positive with EMA, HHV8, LMP1, CD38, CD138, and kappa light chains. They were negative with common lymphoma-associated markers (CD20, CD3, CD15, CD30, CD10, and bcl2). In situ hybridization confirmed the monotypic kappa light chains and the EBV infection (EBER+). A polyclonal pattern of Ig gene rearrangement was detected by PCR analysis. In the adjacent lymph node parenchyma, some germinal centers mimicked Castleman disease. In this case, the differential diagnosis was discussed with an early stage of large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease. The clinical presentation, the immunophenotype, and the molecular results helped to make the accurate diagnosis. Through the review of the nine previously reported cases in literature, we discuss the clinical and pathologic features and the differential diagnosis of HHV8/EBV GLD.