Cold Agglutinin Disease Secondary to Multiple Myeloma in a Psoriatic Patient

Cold agglutinin disease (CAD) is a chronic compensated hemolytic anemia. We report a case of cold agglutinin disease secondary to multiple myeloma (MM) in a patient of erythrodermic psoriasis. The patient presented with acral cyanosis, progressive weakness and generalized desquamating scaly lesions. After confirming the diagnosis (80-90% plasma cells in bone marrow, M- spike in serum protein electrophoresis, G-ë restriction pattern in immune electrophoresis) he was given chemotherapy with CTD (cyclophosphamide, thalidomide and dexamethasone) protocol. His clinical symptoms improved and he has now completed 4 cycles of chemotherapy. The interim follow up showed achievement of PR (partial response).DOI: http://dx.doi.org/10.3329/jom.v15i2.20688 J MEDICINE 2014; 15 : 141-143

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IgM Multiple Myeloma: A Rare Subtype Highly Sensitive to Lenalidomide

Blood ◽

10.1182/blood.v112.11.5220.5220 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5220-5220

Author(s):

Alvaro Moreno-Aspitia ◽

Antony Charles ◽

Tejal Patel ◽

Celine Bueno ◽

Abba Zubair ◽

...

Keyword(s):

Multiple Myeloma ◽

Transient Response ◽

Low Dose ◽

Plasma Cells ◽

Poor Response ◽

Response To Therapy ◽

Bone Lesions ◽

Best Response ◽

M Spike

Abstract Background: IgM multiple myeloma (MM) are very rare plasmaproliferative disorders representing 0.5–1.2% of all cases of MM and < 0.2% of all IgM monoclonal gammopathies. Clinical criterion are not always helpful in differentiating IgM MM from Waldenstrom macroglobulinemia. However, the presence of lytic bone lesions, absence of lymphadenopathy and/or hepatosplenomegaly, presence of translocation of the immunoglobulin heavy chain locus at 14q32 [t(11;14), t(14;16), t(4;14)], and strong expression of CD138 by the plasma cells are useful in the diagnosis of IgM MM. It has been our experience and of others that these cases have an aggressive behavior at presentation, shorter survival than IgG and IgA MM and poor response to therapy for lymphoplasmacytoid lymphomas. We present here 2 cases of IgM MM with a dramatic response to Lenalidomide and low dose dexamethasone (Rev/Dex) Results: Baseline patient characteristics at time of diagnosis of IgM MM and therapy outcome are presented in the following 2 tables: Table 1. Case 1 2 Age and sex 72 (F) 73 (F) Serum M-spike (g/dL) 5.3 6.2 Urine M-spike (mg/dl/24 hrs) 72 412 Serum IgM (mg/dL) 8,590 11,000 BM plasma cells percentage 90 20 Plasma cell immunophenotyping CD138+++, partial CD20, CD56− CD138+++, partial CD20, CD56− Cytogenetics (Standard and/or FISH) Standard: normal FISH: not done on initial biopsy. On follow up there were insufficient number of plasma cells to perform test Standard: of 20 metaphases, 6 had a complex hypotetraploid karyotype with relative loss of 13q, 14, 15, 16, 20, and 22, and numerous unbalanced rearrangements. FISH: a plasma cell clone with monosomy 13 and IGH/c-MAF fusion, t(14;16). In addition, approximately 60% of plasma cells had a tetraploid clone with the same anomalies as well as relative loss of p53 Bone lesions Multiple non-traumatic spinal fractures and of stenum Several lytic lesions of long bones Renal insufficiency No No Anemia (Hbg g/dL) Yes (8.7) Yes (8.1) Hypercalcemia (Ca mg/dL) Yes (12.5) Yes (11.4) Beta 2 microglobulin (mg/dL) 5.79 8.51 Serum viscosity (cpoise) 5.9 4.8 Table 2. Best Response to therapy Case Therapy Best Response Comments 1 Rituxan, then Fludarabine based therapy Transient response Rapid progression after partial and transient response to each therapy 1 Lenalidomide + LD-Dex sCR after cycle #6. Currently on CR 18 months later IgM declined from 8,590 to 43 mg/dL after 4 cycles of Rev/Dex. 2 Lenalidomide + LD-Dex VGPR after cycle #2 IgM declined from 11,000 to 463 mg/dL after cycle 3. Complete disappearance of M-spike in serum; BM to be done after cycle #4 Conclusions: This is the first report that we are aware of a rapid and dramatic response to lenalidomide and low dose dexamethasone in these rare cases of IgM MM with poor response to NHL-type treatment. Lenalidomide-based therapy might abrogate poor prognosis cytogenetics in this unusual subtype of MM (case #2), however, follow up for this patient is still very short.

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The Natural History of Smoldering (Asymptomatic) Multiple Myeloma.

Blood ◽

10.1182/blood.v106.11.3396.3396 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3396-3396 ◽

Cited By ~ 4

Author(s):

Robert Kyle ◽

Ellen Remstein ◽

Terry Therneau ◽

Angela Dispenzieri ◽

Paul Kurtin ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Plasma Cell ◽

Light Chain ◽

Plasma Cells ◽

M Protein ◽

Cell Content ◽

Bone Marrow Plasma ◽

M Spike

Abstract Smoldering multiple myeloma (SMM) is characterized by a serum M protein ≥ 3g/dL and/or 10% or more of plasma cells in the bone marrow. However, the definition is not standardized, and it is not known whether both serum M protein levels and bone marrow plasma cell counts are necessary for diagnosis or if one parameter is sufficient. We reviewed the medical records and bone marrows of all patients from Mayo Clinic seen within 30 days of recognition of an IgG or IgA M protein ≥ 3g/dL or a bone marrow containing ≥ 10% plasma cells from 1970 to 1995. This allows for a minimum potential follow-up of 10 years. Patients with end-organ damage at baseline from plasma cell proliferation, including active multiple myeloma (MM) and primary amyloidosis (AL) and those who had received chemotherapy were excluded. A differential of the bone marrow aspirate coupled with the bone marrow biopsy morphology and immunohistochemistry using antibodies directed against CD138, MUM-1 and Cyclin D1 were evaluated in every case in order to estimate the plasma cell content. In all, 301 patients fulfilled either of the criteria for SMM. Their median age was 64 years and only 3% were less than 40 years of age; 60% were male. The median hemoglobin value was 12.9 g/dL; 7% were less than 10 g/dL, but the anemia was unrelated to plasma cell proliferation. IgG accounted for 75%, IgA 22%, and biclonal proteins were found in 3%. The serum light-chain was κ in 67% and λ in 33%. The median serum M spike was 2.9 g/dL; 11% were at least 4.0 g/dL. Uninvolved serum immunoglobulins were reduced in 81%; only 1 immunoglobulin was reduced in 31% and both were decreased in 50%. The urine contained a monoclonal κ protein in 36% and λ in 18% and 46% were negative. The median size of the urine M spike was 0.04 g/24h; only 5 (3%) were > 1 g/24h. The median bone marrow plasma cell content was 15 – 19%; 10% had less than 10% plasma cells, while 10% had at least 50% plasma cells in the bone marrow. Cyclin D-1 was expressed in 17%. Patients were categorized into 3 groups: Group 1, serum M protein ≥ 3g/dL and bone marrow containing ≥ 10% plasma cells (n= 113, 38%); Group 2, bone marrow plasma cells ≥ 10% but serum M protein < 3g/dL (n= 158, 52%); Group 3, serum M protein ≥ 3g/dL but bone marrow plasma cells < 10% (n= 30, 10%). During 2,204 cumulative years of follow-up 85% died (median follow-up of those still living 10.8 years), 155 (51%) developed MM, while 7 (2%) developed AL. The overall rate of progression at 10 years was 62%; median time to progression was 5.5 yrs. The median time to progression was 2.4, 9.2, and 19 years in groups 1, 2, and 3 respectively; correspondingly at 10 years, progression occurred in 76%, 59%, and 32% respectively. Significant risk factors for progression with univariate analysis were serum M spike ≥ 4g/dL (p < 0.001), presence of IgA (p = 0.003), presence of urine light chain (p = 0.006), presence of λ urinary light chain (p = 0.002), bone marrow plasma cells ≥ 20% (p < 0.001) and reduction of uninvolved immunoglobulins (p < 0.001). The hemoglobin value, gender, serum albumin, and expression of cyclin D-1 were not of prognostic importance. On multivariate analysis, the percentage of bone marrow plasma cells was the only significant factor predicting progression to MM or AL.

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Multiple Myeloma with Suspected Non-Secretory Type

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v27i1.1575 ◽

2020 ◽

Vol 27 (1) ◽

Author(s):

Annisa Ginar Indrarsi ◽

Usi Sukorini

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Monoclonal Gammopathy ◽

Plasma Cells ◽

Immunoglobulin A ◽

Protein Electrophoresis ◽

Palpebral Conjunctiva ◽

General Weakness ◽

M Spike ◽

G Ratio

Multiple Myeloma (MM) is a hematological malignancy characterized by clonal plasma cell in bone marrow that produceabnormal globulin, which resulted in monoclonal gammopathy. Multiple Myeloma Non-Secretory (MMNS) is a very rareform of multiple myeloma with monoclonal plasmocytic proliferation in bone marrow supported by clinical manifestationand radiological findings. However, plasma cells fail to secrete immunoglobulin. A 44-year-old female came to SardjitoGeneral Hospital with main complaints of weakness and back pain. General weakness and pale palpebral conjunctiva were6 observed (+/+), liver and spleen were not palpable. Blood test results were as follows: Hb 3.0 g/dL, RBC 1.07 x 10 / μL, WBC3 3 562 x 10 /μL, PLT 114 x 10 /μL, A/G ratio 1.07, BUN 51.5 mg/dL, creatinine 4.62 mg/dL, and calcium 3.1 mmol/L. Skeletalsurvey suggested a multiple osteolytic. Protein electrophoresis revealed hypogammaglobulinemia with no M-spike. Therewere 66% of plasma cells in bone marrow. Patient was diagnosed by MMNS. Diagnosis MMNS can be established if clonalplasmacytes is accompanied with renal insufficiency and hypercalcemia. However, monoclonal gammopathy was not foundin serum protein electrophoresis. A case reported of 44-year-old female diagnosed as MMNS with 'punched out' multipleosteolytic, increased plasma cells in bone marrow without evidence of paraprotein in circulation proved by low A/G ratio andnegative M-spike.

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Cold agglutinin disease revisited: a multinational, observational study of 232 patients

Blood ◽

10.1182/blood.2020005674 ◽

2020 ◽

Vol 136 (4) ◽

pp. 480-488 ◽

Cited By ~ 4

Author(s):

Sigbjørn Berentsen ◽

Wilma Barcellini ◽

Shirley D’Sa ◽

Ulla Randen ◽

Tor Henrik Anderson Tvedt ◽

...

Keyword(s):

Plasma Cells ◽

Prospective Trial ◽

Response Duration ◽

Northern Region ◽

Cold Agglutinin ◽

Sustained Remission ◽

Cold Agglutinin Disease ◽

Median Response ◽

Increased Risk

Abstract We retrospectively studied 232 patients with cold agglutinin disease (CAD) at 24 centers in 5 countries. In Norway and a northern region of Italy, the study was close to being population-based. For the first time, we demonstrate fourfold differences between cold and warmer climates regarding prevalence (20 vs 5 cases/million) and incidence (1.9 vs 0.48 cases/million per year). Mean baseline hemoglobin level was 9.3 g/dL, but 27% had hemoglobin <8 g/dL. Identification of typical features of CAD-associated lymphoproliferative disorder in the bone marrow was greatly increased by centralized biopsy assessment. CAD seems to be associated with a slightly increased risk of venous thrombosis. This work includes a follow-up study of therapies, focusing on the long-term outcomes of the rituximab plus bendamustine and rituximab plus fludarabine regimens. Rituximab plus bendamustine therapy resulted in responses in 35 (78%) of 45 patients; 24 (53%) achieved complete response. Interestingly, these rates were still higher than observed in the original (2017) prospective trial, and we also found a shift toward deeper responses with time. This is explained by the prolonged time to response seen in many patients, probably related to long-lived plasma cells. In patients responding to rituximab-bendamustine, median response duration was not reached after 88 months, and estimated 5-year sustained remission was 77%. The regimen appeared safe regarding late-occurring malignancies. Rituximab plus fludarabine therapy seems to carry a higher risk of long-term adverse effects.

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Multiple Myeloma Stem Cells and Plasma Cells Display Distinct Drug Sensitivities.

Blood ◽

10.1182/blood.v104.11.2476.2476 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2476-2476 ◽

Cited By ~ 1

Author(s):

William Matsui ◽

Carol Ann Huff ◽

Qiuju Wang ◽

James P. Barber ◽

B. Douglas Smith ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Antitumor Agents ◽

Plasma Cells ◽

Clinical Symptoms ◽

Side Population ◽

Cell Surface Antigens ◽

Intracellular Enzyme ◽

Major Activity ◽

Rpmi 8226

Abstract We recently demonstrated that multiple myeloma (MM) is organized in a hierarchical manner in which clonogenic MM progenitors or stem cells resembling post-germinal B cells give rise to MM plasma cells (PC). To study the potential biologic differences between MM stem cells and MM PC, we examined each cellular subset for characteristics found in normal stem cells as well as their responses to various antitumor agents. The human MM cell lines RPMI 8226 and NCI-H929 were initially studied as we previously found that they recapitulate clinical MM specimens and consist of distinct cell populations based on the expression of the PC surface antigen CD138; CD138+ cells resemble typical MM PC, whereas CD138neg cells express B cell surface antigens and have greater clonogenic capacity. Examination of these cellular subpopulations by flow cytometry demonstrated that CD138neg cells were smaller and less granular by light scatter than CD138+ PC and expressed higher levels of the intracellular enzyme aldehyde dehydrogenase that is present in normal hematopoietic progenitors with self-renewal potential. Furthermore, cells expressing the side population phenotype after staining with the DNA binding dye Hoechst 33342 were exclusively CD138neg. We also investigated the effects of different clinically applicable agents on CD138+ and CD138neg cells. CD138+ and CD138neg cells isolated from RPMI 8226 and NCI-H929 cells by fluorescence activated cell sorting were treated with dexamethasone (dex, 100nM), bortezomib (velcade, 10nM), CC5013 (revlimid, 1μM), rituximab (10μg/ml) or alemtuzumab (campath,10μg/ml) for 72 hours followed by plating in methylcellulose to assess clonogenic capacity. CD138+ PC were significantly inhibited by dex (27 ± 11% recovery compared to untreated control cells), velcade (14 ± 6%) and revlimid (44 ± 27%), whereas rituximab (92 ± 25%) and campath (97 ± 18%) had little activity. In contrast, clonogenic growth of CD138neg cells was not significantly inhibited by dex (82 ± 19%), velcade (88 ± 29%), or revlimid (91 ± 14%), but was significantly decreased by rituximab (63 ± 22%) and campath (47 ± 27%). Similarly, clonogenic MM growth of CD138neg cells from 4 clinical MM samples was not affected by dex (84 ± 9%), velcade (82 ± 24%), or revlimid (93 ± 11%), but was significantly inhibited by rituximab (19 ± 7%) or campath (15 ± 11%). Clonogenic MM precursors may be distinguished from MM PC by a variety of biological parameters typically expressed by normal stem cells. Furthermore, these cellular subsets have different susceptibilities to a variety of clinical agents, and agents with activity against MM PC may be ineffective against MM stem cells. Moreover, agents without activity agasint MM PC may have major activity against MM stem cells. The divergent sensitivities of MM stem cells and PC may explain the dramatic, but transient, responses seen with many agents. Therapeutic strategies that result in long-term remissions may require the inhibition of both MM PC to reduce clinical symptoms and MM stem cells responsible for relapse.

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Phenotypic Analysis of Plasma Cells in Monoclonal Gammopathy and Multiple Myeloma Subjects.

Blood ◽

10.1182/blood.v110.11.4755.4755 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4755-4755

Author(s):

Lucie Kovarova ◽

Ivana Buresova ◽

Ludek Pour ◽

Renata Suska ◽

Zdenek Adam ◽

...

Keyword(s):

Multiple Myeloma ◽

Monoclonal Gammopathy ◽

Plasma Cells ◽

Concentration Level ◽

Newly Diagnosed ◽

Phenotypic Analysis ◽

Benign Monoclonal Gammopathy ◽

Unknown Significance ◽

Population Ratio

Abstract Introduction: Multiple myeloma (MM) is a B-cell neoplasia caused by the proliferation of clonal plasma cells (PCs). MM and benign monoclonal gammopathy of unknown significance (MGUS) are routinely distinguished on the basis of paraprotein concentration, level of PCs infiltration and the presence or absence of other clinical features. Flowcytometric detection of PCs according to the expression of CD38 and CD138 has limitation in discrimination between normal and abnormal PCs, but this is possible in multicolor phenotypic analysis. The aim of this study is to compare the numbers of normal and abnormal PCs in MGUS and MM subjects and to find some parameter useful for evaluation PCs distribution. Materials and methods: 51 newly diagnosed untreated MM patients (63,9±10,0 years old) and 31 non-treated MGUS subjects (64,2±13,8 years old) were analysed. Lysed whole bone marrows were analysed by flowcytometric immunophenotyping and PCs were indentified by expression of CD38, CD138, CD45 and also CD56 and CD19. Results: Discrimination between normal CD19+ PCs and abnormal CD56+ PCs was done on CD38+CD138+ population. Ratio of normal PCs count and abnormal PCs counts (normal/abnormal=N/A) was used to describe a distribution of PCs. Subjects with MGUS had 0,97±1,65% (average±SD) of CD38+CD138+ cells (median 0,45; range 0,03–7,47%) with average N/A ratio 2,91±3,94 (median 1,36; range 0,01–18,44). Newly diagnosed MM patients had 4,96±9,94% of CD38+CD138+ cells (median 0,85; range 0,02–41,80%) with average N/A ratio 1,70±3,03 (median 0,13; range 0–11,5). In 9,7% MGUS subjects evaluation of distibution of PCs showed transformation of MGUS into MM. In some newly diagnosed MM patients (31,4%) CD38+CD138+ plasma cells were positive for CD19 although they were aberrant and these PCs were mostly CD45+. In some patients (9,7% of MGUS; 17,6% of MM) PC did express neither CD19 nor CD56 and this fact may complicate further evaluation of PCs. Conclusions: Results confirmed that in MGUS subjects we can find lower numbers of PCs which are mostly CD45+CD19+. A majority of plasma cells in newly diagnosed MM patients are abnormal CD56+ PCs and these plasma cells are usually CD45−. Further follow-up of patients can confirm the N/A ratio as a predictive factor for transformation of MGUS into MM and its value for evidence of relapse or progression to active myeloma.

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Serum Free Light Chain Ratio in Distinguishing Smoldering Multiple Myeloma From Active Multiple Myeloma,

Blood ◽

10.1182/blood.v118.21.3948.3948 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3948-3948

Author(s):

Jeremy T Larsen ◽

Shaji Kumar ◽

S. Vincent Rajkumar

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Predictive Value ◽

Plasma Cells ◽

Organ Damage ◽

End Organ Damage ◽

Cut Point ◽

Smoldering Multiple Myeloma ◽

Bone Marrow Plasma

Abstract Abstract 3948 Background: Smoldering multiple myeloma (SMM) is an asymptomatic precursor disease of multiple myeloma, and is defined by excess bone marrow plasma cells and monoclonal protein without evidence of end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions [CRAB]). The identification of SMM patients with more aggressive underlying disease remains a challenge. We hypothesize that SMM is a clinical entity comprised of both premalignant, high-risk MGUS and early multiple myeloma in transition to malignant disease, which may be differentiated with the use of the serum FLC (FLC) ratio. Methods: This was a retrospective analysis of 586 patients with newly diagnosed SMM from 1970–2010 with available stored serum samples around the time of diagnosis to be utilized for quantification of FLC ratios. SMM was defined by the International Myeloma Working Group 2003 definition; serum M-protein ≥ 3 g/dL and/or ≥ 10% bone marrow plasma cells with no evidence of CRAB features. The immunoglobulin FLC assay (Binding Site, U.K.) was used for testing. The FLC ratio was calculated as κ/λ (reference range 0.26–1.65). The involved/uninvolved FLC ratio was recorded to simplify the reporting of data. Receiver Operating Characteristics (ROC) curves were created to assess the ability of the FLC ratio to discriminate patients who progressed to symptomatic multiple myeloma (MM) in the first 2 years or at any point during follow-up versus patients without evidence of progression. Patients with less than 24 months follow-up without progression were censored. The optimal diagnostic cut-point for FLC involved/uninvolved ratio to identify patients with progressive disease from the ROC curve was >88.6 (equivalent to <0.011 or >88.6). For ease of clinical application, the optimal value for involved/uninvolved FLC ratio was rounded to >100. Time to progression (TTP) from date of the initial FLC to active MM was calculated using Kaplan-Meier analysis and compared to patients with a high (>100) and low (<100) involved/uninvolved FLC ratio at time of SMM diagnosis. TTP within 24 months of the initial FLC was also calculated. Results: During the study period, 54% of patients progressed to active MM. On ROC analysis, a cut-point of >100 corresponded to a sensitivity of 25% (95% CI, 20.5–30.4) and specificity of 99.3% (97.3–99.9), with positive likelihood (+LR) ratio of 33.9 (38.1–41.0), negative likelihood ratio (−LR) of 0.75 (0.2–3.0), positive predictive value (PPV) of 97.6 (91.5–99.7) and negative predictive value of 53.0 (48.5–57.4). Using the ROC to assess progression to MM within 24 months (Figure 1), sensitivity was 29.6% (23.5–36.4), specificity 94.5% (91.7–96.5), +LR 5.36 (4.3–6.6), -LR 0.75 (0.5–1.1), PPV 85.8 (77.7–91.8), and NPV 54.3 (49.8–58.9). Median TTP to active MM in the FLC >100 group was 15 months (9–17) versus 52 months (44–60) in the FLC <100 group (p <.0001) [Figure 2]. In the FLC ratio >100 group, progression at 1 year was 47%, 76% at 2 years, and 90% at 3 years. Only 25% of the FLC <100 patients had progressed at 2 years. The most common progression event was bone disease (42%), followed by anemia (26%), renal impairment (23%), and hypercalcemia (5%). Conclusion: Elevation of the FLC ratio >100 (or <0.01) is highly specific for the future development of active MM, with 76% of these patients developing end-organ damage requiring therapy within 2 years. Risk of transformation to MM in the FLC <100 group was similar to previously reported rates of 10% per year for the first 5 years. Development of an FLC ratio >100 is associated with increasing disease burden and in this study behaved in a malignant fashion rather than a precursor state. The FLC is a simple and useful predictor of progression to MM in SMM, and patients with FLC ratios of <0.01 or >100 within the first 2 years of SMM diagnosis should be monitored especially closely. Future studies are needed to determine optimum cutoffs for FLC ratio to where a change in definition of MM could be considered. Disclosures: No relevant conflicts of interest to declare.

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Initial Presentation Of Multiple Myeloma As Intraparenchymal Brain Mass

Blood ◽

10.1182/blood.v122.21.5402.5402 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5402-5402

Author(s):

Ishan Malhotra ◽

Abhinav B. Chandra ◽

Yiwu Huang

Keyword(s):

Central Nervous System ◽

Multiple Myeloma ◽

Nervous System ◽

Ct Scan ◽

Plasma Cells ◽

Light Chains ◽

Left Lateral Ventricle ◽

Pet Ct ◽

M Spike ◽

Pet Ct Scan

Abstract Case presentation 38 year old African female presented with complaints of severe headache which had started couple of weeks prior to presentation and was progressively becoming worse. Patient underwent a CT scan of the head which revealed a 3.2 X 3.3 X 3.7 cm lobulated hyperdense periventricular mass in the left temporoparietal area with surrounding vasogenic edema with mass effect on the adjacent left lateral ventricle and 0.6 cm midline shift to the right with uncal herniation and effacement of left cerebral peduncle with dilatation of left temporal horn. MRI of the brain revealed a 3.1 X 2.6 X 3.6 cm lobulated mass in left lateral ventricle trigone. Radiologically, differential diagnoses included intraventricular meningioma, lymphoma, choroid plexus papilloma or metastasis. Patient underwent left craniotomy for tumor resection. Patient had an uneventful post-operative recovery and the resected tumor was high grade malignant neoplasm with plasmablastic features and immunohistochemical stains revealed that the tumor cells were positive for CD138, CD30, MUM-1, Bcl-2, vimentin and lambda light chains and were negative for kappa light chains, CD3, CD20, PAX-5, CD79a, GFAP, cytokeratin, AE1/AE3, synaptophysin, chromogranin, EMA, S-100, Melan-A, CD45, CD56 and EBV(EBER-ISH). Ki-67 was about 80%. Serum protein electrophoresis (SPEP) was sent that showed an M-spike of 3.3 g/dl that was IgG lambda. A bone marrow biopsy showed 100 % infiltration with plasma cells. Patient underwent a CT chest/abdomen/pelvis and a PET/CT scan which revealed multiple scattered subcutaneous masses throughout the body and an asymptomatic mass near spinal cord at C1. Patient was treated with VTD-PACE regimen (bortezomib, thalidomide, decadron, cisplatin, liposomal doxorubicin, cyclophosphamide, and etoposide). She received two cycles of VTD-PACE chemotherapy regimen with excellent response to the treatment. Her M-spike protein which prior to treatment was 3.3 g/dl disappeared after second cycle of chemotherapy and her subcutaneous lesion also dramatically improved on repeat PET/CT scan. The C1 dural lesion also had significant improvement after the chemotherapy. Her IgG also decreased from 5070 mg/dl to 791 mg/dl. She was referred for autologus stem cell transplant. She was subsequently started on weekly cyclophosphamide, bortezomib and decadron. Discussion Malignancies of plasma cells comprise 1% of malignant neoplasms which includes multiple myeloma, solitary plasmacytomas (including solitary bone plasmacytoma and extramedullary plasmacytomas) and immunoglobulin deposition syndromes. Central nervous system (CNS) involvement of multiple myeloma itself is not a common entity. Fassas et al. published data of 18 cases over a course of 10 years. Gozzetti et al. published their data of 50 patients in 2012. Of these 50 patients, 76% had osteo-dural or primary dural multiple myeloma (OD-DMM) and 24% had central nervous system myelomatosis. They found that patients treated with novel agents had better outcome than patients treated with conventional drugs. Cases with initial presentation of intracranial plasmacytomas are even rarer. Patients with CNS myeloma have poor prognosis with median survival being around 4- 5 months. Our patient had excellent response with two cycles of VTD-PACE regimen with negative M-spike, normalization of IgG and decrease in size of subcutaneous nodules and C1 spinal lesion. She has survived for 5 months without autologus transplant and is currently on weekly cyclophosphamide, bortezomib and decadron. Disclosures: No relevant conflicts of interest to declare.

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Incidence of Thromboembolic Events Is Increased in a Retrospective Analysis of a Large Cold Agglutinin Disease (CAD) Cohort

Blood ◽

10.1182/blood.v130.suppl_1.928.928 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 928-928

Author(s):

Catherine Broome ◽

Julia M Cunningham ◽

Megan Mullins ◽

Xiaohui Jiang ◽

Lauren Bylsma ◽

...

Keyword(s):

Clinical Manifestations ◽

Patient Characteristics ◽

Immunoglobulin M ◽

Cold Agglutinin ◽

Occurrence Rate ◽

Thromboembolic Events ◽

Cold Agglutinin Disease ◽

Medical Claim ◽

Complement Activity

Abstract Introduction: Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia (AIHA) with a prevalence of approximately 16 patients per million. CAD accounts for less than 20% of all AIHA and is characterized by immunoglobulin M (IgM) mediated agglutination of erythrocytes and subsequent activation of the classical complement pathway. In addition to hemolysis, which can vary from mild to severe, clinical manifestations of CAD have been reported to include livedo reticularis, acrocyanosis, circulatory symptoms and cutaneous necrosis (Swiecicki, P Et al Blood 2013). The rarity of this disease has resulted in a lack of data regarding its natural history. Thromboembolic events (TEs) are a known complication of other hemolytic disorders, however, little is known about its incidence and severity in CAD. We evaluated the largest cohort of CAD patients to date and compared them to a matched non-CAD cohort to evaluate clinical characteristics and occurrence rate of TEs. Methods: Patients were identified from the Optum-Humedica database, containing de-identified information on claims, medications, lab results, diagnoses, procedures and clinical notes for individuals from all 50 states. The presence of "cold agglutinin disease" must have appeared in their medical record on at least 3 separate dates from 2006-2016. Patients with "cold agglutinin disease" documented on 1 or 2 dates were included only after an independent review and agreement by 2 hematologists. A comparison cohort was identified from the database and matched on gender, race, region, overall follow-up time, age, and entry date into the health plan. Patient characteristics, TEs, treatment with rituximab, and lab parameters [hemoglobin (Hgb), bilirubin, lactate dehydrogenase (LDH)] were evaluated. LDH and bilirubin were included as they represent hemolysis and indirect measures of complement activity in CAD. TEs in both cohorts were identified from claims submitted. Results: 814 patients with CAD and 7,960 comparisons were identified. Median follow-up time for CAD patients was 75.6 months (0-125 months). Seventy percent of CAD patients were over 65 years of age, 62% were women and 84% were Caucasian. Forty-four percent of CAD patients reside in the midwest, 13% in the northeast, 29% in the south, 12% in the west, with 2% unknown. Thirty-one percent of CAD patients had a medical claim for any form of TE compared to 20% in the matched comparisons (p < 0.0001). Eighteen percent of CAD patients had 1 TE compared to 14% of the matched comparisons (p < 0.001). Thirteen percent of CAD patients had 2 or more types of TEs compared to 6% of matched comparisons (p < 0.001). Nearly 10% of all CAD patients had a venous TE compared to 3% of matched comparisons (p < 0.0001). Twenty five percent of all CAD patients had a cerebral TE compared to 16% of matched comparisons (p < 0.0001). Eight percent of all CAD patients had an arterial TE compared to 5% of matched comparisons (p < 0.0001). Of the 94 CAD patients that had available Hgb within a month prior to a medical claim for a TE, 47% had mild anemia (Hgb > 10 g/dL), 29% had moderate anemia (Hgb 8.1-10 g/dL) and 24% had severe anemia (Hgb < 8 g/dL). Forty-one of the 94 patients had LDH and bilirubin values documented within one month of a medical claim for TE. Ninety percent of these CAD patients had evidence of ongoing hemolysis, represented by an abnormal bilirubin or LDH. Seventy-nine percent of CAD patients treated with a rituximab-containing regimen had an abnormal bilirubin or LDH within 12 months of completion of therapy. Conclusion: Thromboembolic events have been an under-appreciated complication of CAD. Patients with CAD had a significantly higher overall incidence of TEs compared to matched comparisons including venous, arterial, and cerebral events. Furthermore, patients with CAD also had a higher incidence of more than one type of TE. The severity of anemia does not appear to predict TE risk, whereas markers of hemolysis (LDH/bilirubin) do. Standard therapy with rituximab did not result in sustained control of hemolysis, as demonstrated by abnormal bilirubin and LDH values in a majority of patients within 12 months of last dose. Therapeutic modalities that can quickly and completely inhibit complement activity in CAD may offer clinical benefits beyond correcting hemolysis and anemia, such as decreasing TE risk. Disclosures: This study was funded by True North Therapeutics, Inc., a Bioverativ Inc. company Disclosures Broome: TrueNorth Therapuetics: Honoraria; Alexion Pharmaceuticals: Honoraria. Cunningham: TrueNorth therapeutics: Honoraria. Rosenthal: Bioverativ Inc: Employment.

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The Prognostic Significance of Minimal Residual Disease Detection after Induction and ASCT to the Patients with Multiple Myeloma

Blood ◽

10.1182/blood-2018-99-118257 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4956-4956

Author(s):

Weiqin Yao ◽

Zhu Mingqing ◽

Yao Feirong ◽

Lingzhi Yan ◽

Song Jin ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Minimal Residual Disease ◽

Induction Therapy ◽

Plasma Cells ◽

Residual Disease ◽

Prognostic Significance ◽

Depth Of Response ◽

Minimal Residual

Abstract Objective: In the last decade the outcome in multiple myeloma in CHINA has greatly improved due to the new, effective therapies including PIs and Imids. But responses to treatment and survival remains heterogeneous because of patient characteristic, disease biology and mechanisms of drug resistance. More and more studies have established the link between depth of response and improved PFS and OS. multiparameter-flow cytometry (MFC) is a main method to detect minimal residual disease(MRD) in myeloma. Sensitivity will be at least at 10-4 to 10-5 by 10-color MFC. Imaging techniques such as PET-CT are important for EMD and bone MRD detection. whole body DWI-MRI is a new imaging technique by mean of the apparent diffusion coefficient(ADC) which can qualify the depth of response to antineoplastic treatment. This study was designed to evaluate the prognostic significance of MRD by 10-color MFC and imaging to the MM patients after induction.Methods: 102 patients with newly diagnosed MM were enrolled at the First Affiliated Hospital of Soochow University from July 2015 to July 2017. All patients were diagnosed and the response were assessed by IMWG criteria. The median of age was 58 (31-75).There were 46 patients with IgG type , 24 IgA , 14 light chain, 18 others. 34 Patients in ISS stageⅠ,34 in stage Ⅱ, 30 in stage Ⅲ. All patients received 4-6 cycles of triplet bortezomib based or lenalidomide based induction therapy. Transplantation available patients received APBSCT with BUCY condition followed by 4-6 cycles of bortezomib based or lenalidomide based consolidation which were given to transplantation unavailable patients too. Lenalidomide and thalidomide were used for over 2y of maintenance therapy. Bone marrow aspirates for MRD imaging MRD assessment were obtained at the end of induction and 1year after ASCT.The median of follow-up was 13 (2-29) months.Results: According to MRD by MFC and imaging after induction therapy and 1 year after ASCT, the patients were divided into different groups. MFC negativity was 33%(29/88) after induction therapy compared with 63%(32/51) after ASCT (X2=11.636,P=0.001). After induction therapy, the median PFS was 22 months for MRD positive group compared with not reached with MRD negative group by MFC (P=0.042) in patients with very good partial remission(VGPR) and above. The 2 years PFS was 100% for those with MRD negative compared with 60% for MRD positive by imaging. The 2 years PFS was 80% for those have multiclonal normal plasma cells compared with 52.6% for those without. The median PFS was not reached for MFC MRD negative patients 1 year after ASCT compared with 20 months for positive patients. (P=0.002). Multivariate analysis including high risk cytogenetics(17p-, t(4;14), t(14;16)), sex, age, ISS, chemotherapy, ASCT, CR/VGPR, normal PCs showed that the MFC MRD and ASCT were independent prognostic factor.Conclusions: Patients with MFC MRD negative after induction therapy or ASCT is a better prognostic marker than CR or even the best marker. Imaging MRD negativity and the appearance of normal plasma cells in the bone marrow suggests a better prognosis.We will have a try to do more research on overall survival(OS),include longer follow-up and a larger number of patients enrolled. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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