Cases Of Plasma Cell Dyscrasia Research Articles

A profile of hematological malignancies diagnosed in a tertiary care center of Assam: Highlighting the experience from a resource constraint perspective

Background: Hematological disorders require a systematic approach, from clinical examination to a complete blood count, followed by a bone marrow study for diagnosis. To effectively plan, treat, and prognosticate, immunophenotyping and molecular studies are essential to incorporate. Aims and Objectives: The aim of our study is to understand the pattern of neoplastic hematological conditions encountered in Assam and share our experience during the diagnosis. Materials and Methods: This was a single-centered, observational study carried out for 18 months (January 2022–June 2023). A thorough hematological workout was done, including cytochemical staining and conventional polymerase chain reaction for the BCR-ABL transcript, after satisfying inclusion and exclusion criteria. The data were analyzed and correlated before arriving at the final diagnosis. Results: The total of 38 neoplastic cases confirmed by bone marrow study. Out of 38 cases, 14 were chronic myeloid leukemia, 10 were chronic, 4 were in the blastic phase, and BCR-ABL was positive in 13 cases. Two cases were pediatric, of which 1 was in the blastic phase. All 8 cases of plasma cell dyscrasia presented with anemia, bone lesions, and hypercalcemia. The acute leukemia category consisted of 4 acute myeloid leukemia cases, of which 1 was acute promyelocytic leukemia. A total of 10 acute lymphoblastic leukemia (ALL) cases, where 1 case was T-ALL and the rest was B-ALL. Two cases showed a subleukemic presentation in peripheral blood. Conclusion: The experience of pathologists and their meticulous approach can greatly aid in accurate diagnosis, but the immunophenotyping facility and molecular hematology setup can provide most of the relevant information for the best decision-making.

Reactive bone marrow plasmacytosis: A common denominator with diverse etiology

Background and Aims: Reactive plasmacytosis (RP) is characterised by the diffuse distribution of mature polyclonal plasma cells in the bone marrow (BM) and it is known to occur in various disorders. These need to be differentiated from the clonal plasma cell dyscrasias (PCD). We aim to study the morphological features of RP and to help differentiate them better from PCD. Materials and Methods: We analysed 1409 consecutive BM aspirates for the percentage of plasma cells along with the associated clinical findings. The study group included cases with BM RP and the polyclonality being supported by serum protein electrophoresis or by kappa/lambda immunohistochemistry on BM biopsy. The clinical records, haemogram and BM aspiration findings were retrieved and reviewed in all cases. Morphological features of RP cases were analysed in detail. Further, these cases were compared with 10 confirmed cases of PCD in an attempt to distinguish between the two on morphology. Results: A total of 210 BM aspirates showed increased plasma cells (>3.5%). Clonality could be proven in 135 cases, of which 98 cases were polyclonal and 37 were PCD. Majority of RP cases were >40 years with male predominance. The plasma cell concentration in RP ranged from 4% to 25%. The associated diseases included infections followed by autoimmune diseases. On the morphology, RP unveiled scattered, non-aggregated mature plasma cells while in PCDs, there was a mixture of both immature and mature forms including plasmablasts with frequent clustering. Conclusion: A number of diseases show increased percentage of plasma cells in BM raising suspicion of PCD. It may be difficult to distinguish reactive from neoplastic conditions as there is an overlap both in cell counts and morphology. Assessment of subtle morphological features along with associated clinical and laboratory findings are cardinal for making a correct diagnosis.

Evolution of Monoclonal Gammopathy of Undetermined Significance in Kidney Transplant Recipients at the CHUM (Centre Hospitalier de l'Université de Montréal) — a Single-Institution Retrospective Study

IntroductionRecommendations guiding the care of patients with monoclonal gammopathy of undetermined significance (MGUS) in the setting of kidney transplant are scarce. Nevertheless, monoclonal gammopathies carry a risk of neoplastic progression to hematologic malignancies and may induce renal injury from their deposition in the kidney (monoclonal gammopathy of renal significance - MGRS). However, it remains largely uncertain if these considerations translate into adverse outcomes in the setting of transplantation, as immunosuppression might favor malignant evolution of MGUS or, alternatively, a nephrotoxic paraprotein could lead to graft loss.MethodsWe conducted a retrospective review of the medical records of patients who received a kidney transplant at our institution between Jan 1, 2000 and Jan 1, 2016. We included patients with at least one available serum protein electrophoresis at any time before or after transplantation. Exclusion criteria consisted of age < 18 years at the time of transplant, no follow-up at our center, multiorgan transplant (liver, lung, pancreas, heart), as well as first transplant prior to study period or presence of any plasma cell malignancy before transplant. Outcomes of interest included paraprotein evolution, appearance of hematologic malignancy, graft rejection and loss. Chi-square tests and Fischer's exact probability test for categorical data and Student's t test for continuous variables were used to assess statistical significance.ResultsOut of 1009 eligible transplant recipients, 755 patients were included in our study based on our inclusion and exclusion criteria. Thirteen patients were found to have MGUS prior to transplant and a monoclonal gammopathy appeared in 43 patients after transplant corresponding to a 5-year incidence rate of 2.7%. Median patient follow-up was 7.5 years. Of the patients with MGUS prior to transplant, 2 developed light chain deposition disease (LCDD) after a follow-up of 1 and 2 years and 2 evolved to smoldering multiple myeloma (SMM) at 1 month and 4 years post-transplant. Of the 43 patients who developed MGUS after transplant, 1 transformed into multiple myeloma (MM) 8 years later and 1 progressed to LCDD 2 months after transplant. None of the 6 patients who evolved to malignancy after transplantation had a systematic hematologic workup prior to allograft implantation questioning whether SMM or MGRS may have already been present before transplant. Figure 1 summarizes the evolution of monoclonal gammopathies in our study population. Of monoclonal gammopathies appearing after transplantation, most remained stable (n=26, 60%) and 9 (21%) were found to be transient. Median size was 0.76 g/L (range 0.1 - 21.6 g/L). Twenty-two (74%) were of IgG isotype and an abnormal kappa/lambda ratio was present in 6 cases (14%). We conducted a univariate analysis to compare allograft outcomes between patients who developed post-transplant MGUS (n=43) and patients who did not (n=699). No differences in induction immunosuppression, occurrence of graft loss (18% and 11%, p=0.14) and acute rejection rates (26% and 27%, p=0.866) were observed between these two groups, respectively. However, the former were found to have an increased risk of CMV (26% and 12%, p=0.01) and polyoma BK virus (26% and 14%, p=0.04). Of note, 7 cases of post-transplant lymphoproliferative disorder (PTLD) were identified in our study population and none was preceded by MGUS.ConclusionOur study suggests a reassuring evolution of true MGUS in the setting of renal transplantation. Indeed, the cases of plasma cell malignancies diagnosed in transplant recipients may have already been present before transplant, yet undetected from lack of systematic investigation. We therefore highlight the importance of identifying and diligently investigating monoclonal immunoglobulins in transplant candidates. If a paraprotein is found before transplant, further investigations with bone marrow biopsy and review of native kidney biopsy appear warranted in order to identify cases of plasma cell dyscrasias (such as SMM) and MGRS prior to transplant. Additionally, MGUS arising after transplant appear to carry a favorable evolution. They also tend to be transient and their appearance may be related to prior CMV and BK virus infections. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Role of serum protein electrophoresis in clinically suspected cases of plasma cell dyscrasia

Background: Serum protein electrophoresis (SPE) and its pattern recognition is an excellent screening technique for the detection of paraproteinemias or monoclonal gammopathies. In this study, we assessed SPE patterns in all clinically suspected cases of plasma cell dyscrasia with usual and unusual clinical presentations and correlated with ancillary investigations. Method: We analysed serum protein electrophoresis (SPE) patterns in clinically suspected cases of plasma cell dyscrasia in 2 year duration. Based on SPE pattern these cases were divided into two groups: Group I, with M-component and Group II, without M-component. These cases were reviewed with respect to clinical presentation and correlated with immunofixation electrophoresis and bone marrow aspiration/biopsy findings wherever available, especially in the M band positive cases to differentiate multiple myeloma (MM) from the other conditions. Result: A total of 80 samples were received for SPE, out of these, 56.3% were clinically suspected to have plasma cell dyscrasia. Among these cases 60% were in group I and 40% were in group II. In group II, 39% cases were essentially non neoplastic after relevant investigations. In group I, M-band was observed in 88.9% cases in γ-region and 11.1% cases in β-region. The mean fraction of the M protein was 4.7g/dl with a range of 2.0g/dl to 9.8g/dl. In group II 72.2% showed polyclonal hypergammaglobulinemia, 22.2% showed normal electrophoretic pattern and 5.6% showed hypogammaglobulinemia. Bone marrow aspiration and biopsy were available in 88.9% of all suspected cases. Various haematological neoplasms observed in both the groups, their clinical presentations with interesting facets of the cases have been discussed. Conclusion: Serum protein electrophoresis is one of the most important diagnostic modality in clinical chemistry. It helps to resolve cases with bone marrow plasmacytosis particularly in differentiating between reactive non-neoplastic plasmacytic proliferations from clonal plasma cell disorders. Moreover, it also facilitates the work-up of cases with atypical presentations and thereby paves way to clinch the diagnosis in these ambiguous cases.

MIELOMA MULTIPEL NONSECRETORY (Nonsecretory Multiple Myeloma)

The incidence of non-secretory multiple myeloma ranged between 1−5% cases of plasma cell dyscrasia (PCD). In the developedcountries like in Europe, cases of MM ranged from 4.5 up to 6.0/100.000 population/year with a median age at diagnosis between63 and 70 years. A very rare disease with difficulties in diagnosis in the clinical practice is the main reason for reporting this case.A nonsecretory MM (MMNS) case was reported in a 36–year-old male with multiple osteolytic lesions and bone pain; whereas renalinsufficiency as well as anemia was not found. The protein electrophoresis result showed a presence of hypoglobulinemia. On bone marrowaspiration (BMA) there was an infiltration of about 40% of plasma cells. Nonsecretory was due to a disruption of immunoglobulinsecretion, so M protein was not found in immuno-fixation electrophoresis. Epidemiological data showed that the incidence of MM inyoung age is very low. The diagnosis of MMNS is established when a plasmocyte neoplasm is not accompanied by renal insufficiency,hypercalcemia and decreased levels of normal immunoglobulin.

Correlation of prothrombin time and activated partial thromboplastin time with serum immunoglobulins in newly diagnosed patients with plasma cell dyscrasias: an experience from tertiary care centre

Background: Plasma cell dyscrasia (PCD) is the term used to describe the disorders characterized by neoplastic proliferation of plasma cells with the abnormal production of immunoglobulins (Ig). Patients with multiple myeloma frequently have abnormal coagulation tests. Aim of the present study were to correlate prothrombin time (PT) and Activated Partial Thromboplastin time (aPTT) with Ig concentrations in patients with newly diagnosed with PCD and to compare PT and aPTT values in untreated and treated patients diagnosed with PCDMethods: This study was conducted in the department of clinical hematology of SKIMS, a tertiary care hospital in northern India from 2015 to 2016. Patients diagnosed with PCD were advised for coagulogram (PT, aPTT) as a base line investigation. A total of 72 patients were included in the study.Results: 37% of multiple myeloma cases (newly diagnosed) and 22% of light chain disease patients presented with prolonged PT whereas none of the patients in treated cases of PCD had prolonged PT. The mean Ig concentration was significantly higher in patients with prolonged PT and aPTT compared to that of patients with normal PT and aPTT values. In IgA myeloma, the mean immunoglobulin concentration was 3643 mg/dL with a mean PT and aPTT values of 18.8s and 36.6 (p value: 0.006). The mean free light chain concentration in kappa (k) light chain myeloma was 1727 mg/L with a mean PT value of 20.5 s, mean aPTT value of 37.4 s (p-value: 0.026).Conclusions: Patients with newly diagnosed myeloma presented with prolonged PT as compared to the treated cases. Also, mean Ig concentration was significantly higher in patients with prolonged PT and aPTT compared to that of patients with normal PT and aPTT values.

Genetic abnormality in 101 cases of plasma cell dyscrasias by FISH technology and cytogenetic examination

To investigate several abnormal genes by the fluorescence in situ hybridization (FISH) in multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS) and reactive plasmacytosis (RP), and to increase the diagnosis and differential diagnosis levels for these common plasma diseases. The clinical manifestations, image and laboratory tests and the FISH detection were retrospectively analyzed in 61 cases of newly diagnosed MM, 20 cases of MGUS and 20 cases of RP from August, 2012 to February, 2015 in the Xiangya Hospital of Central South University. Fifty cases among 61 MM patients showed genetic abnormality by FISH technology. The total positive rate was 81.9%. Among them, 19 cases (31.1%) had 1q21 amplification, 18 cases (29.5%) lacked D13S319, 10 cases (16.4%) missed RB1, 10 cases (16.4%) had IGH translocation and 7 cases (11.4%) lacked p53 gene. The positive rate for two or more genes abnormal was 19.8% in 12 cases. However, in 20 cases of MGUS patients, the positive detection rate was 25%, including 4 cases (20%) of 1q21 augmentation and 2 cases (10%) of IGH translocation. There were not two or more abnormal genes in one case. While in RP cases, only 1 case of patients had D13S319 abnormal gene, and the positive rate was only 5%. There was significant difference (P<0.05) among the 3 groups. The positive detection rate is 81.9% in MM patients by FISH, which is significantly higher than that in patients with MGUS or RP. FISH technology can detect a variety of abnormal genes in MM. It is useful for the differential diagnosis and prognosis for MM, MGUS and RP.

Acute Abdominal Pain Revealing a Primary Plasma Cell Leukemia: A Rare and Aggressive Case of Plasma Cell Dyscrasia

Primary plasma cell leukemia is a rare and aggressive form of plasma cell neoplasm characterized by the presence of circulating plasma cells in peripheral blood. Here, we report an interesting case of a patient with primary plasma cell leukemia, who was diagnosed during postoperative period after surgery for acute appendicitis. After the appendectomy, the patient developed leukocytosis of 41.2×109/L with a high number of circulating plasma cells (32.5×109/L). The immunophenotypic analysis of leukemic plasma cells indicated the following antigen profile: CD138âoâoâo, CD38âoâoâo, IgMcâo, CD56¯ and CD20⁻. Electrophoresis showed a monoclonal IgG component of 5810 mg/dL, and diagnosis of primary plasma cell leukemia was established. After the induction chemotherapy with cyclophosphamide, bortezomib and dexamethasone, the patient achieved partial response with regression of hepatomegaly and decreased pleural effusion. Nevertheless, the patient died of sepsis. Therapy with proteasome inhibitors and stem cell transplantation may also provide increased survival and improve the prognosis of patients with primary plasma cell leukemia.

Primary Plasma Cell Leukaemia with Unusual Presentations: A Case Series

We present here three cases of plasma cell dyscrasias; first case presenting as primary plasma cell leukemia showing unusual morphology and aberrant expression of myeloid markers; the second case presenting as plasma cell leukaemia with atypical plasma cells in peripheral blood and the third case presenting as myelomatous pleural effusion after treatment for myeloma.

Two Cases of Plasma Cell Dyscrasias With Systemic Involvement of Breast

At times we encounter clinical problems for which there are no directly applicable evidence-based solutions, but we are compelled by circumstances to act. When doing so we rely on related evidence, general principles of best medical practice, and our experience. Each “Current Clinical Practice” feature article in Seminars in Oncology describes such a challenging presentation and offers treatment approaches from selected specialists. We invite readers' comments and questions, which, with your approval, will be published in subsequent issues of the Journal. It is hoped that sharing our views and experiences will better inform our management decisions when we next encounter similar challenging patients. Please send your comments on the articles, your challenging cases, and your treatment successes to me at dr.gjmor ris@gmail.com. I look forward to a lively discussion. Gloria J. Morris, MD, PhD Current Clinical Practice Feature Editor

Induction Therapy for Gamma-Heavy Chain Disease with Bortezomib and Dexamethasone: A Case Report

Abstract 5051Heavy chain diseases (HCD) are rare B-cell lymphoproliferative disorders characterized by production of a monoclonal immunoglobulin without a light chain. Three subtypes are known based on the type of monoclonal immunoglobulin produced ie. alpha-heavy chain, gamma-heavy chain and mu-heavy chain disease in order of decreasing frequency. Here we report a case of gamma-heavy chain disease in a previously healthy 48 year old African American man, which demonstrated clinical and pathologic response to treatment with bortezomib and dexamethasone.The patient was transferred to our institution for work-up of persistent high fever, hypotension and eosinophilia after a thorough negative infectious and rheumatologic work-up spanning two outside hospital admissions. The patient had originally presented with two months of constitutional symptoms and cough refractory to antibiotics and prednisone. His outside hospital admissions were notable for an RCA NSTEMI (an unexpectedly large thrombus was noted on cardiac catheterization), eosinophilia and persistent fevers to 105 degrees Fahrenheit. Imaging studies included a CT torso and tagged WBC scan which were unrevealing but for mild splenomegaly of 15 cm and notably did not show lymphadenopathy, masses or evidence for infection. The fevers transiently abated with an empiric course of steroids but recurred accompanied by shock, which responded to a pulse of high dose methylprednisolone. Ultimately he was felt to have primary adrenal insufficiency without evidence of infiltrative disease on dedicated CT. On presentation to our hospital, his initial labs showed WBC 5. 3 K/uL (83% neutrophils, 10% lymphocytes, 3% monocytes, 4% eosinophils), Hb 11. 2 g/dL, platelets 173 K/uL. Comprehensive chemistry profile was unremarkable. SPEP/IFE of the serum and urine revealed a monoclonal gamma-heavy chain without associated light chain. The total IgG was elevated at 2522 mg/dL, IgA was mildly depressed at 57 mg/dL and IgM was normal at 147 mg/dL; the monoclonal protein itself could not be quantitated; hence, total serum IgG was followed. The patient underwent a bone marrow biopsy and aspiration which showed trilineage hematopoiesis, marked esosinophilia, no evidence of leukemia or lymphoma, 10% CD138+ plasma cells, with the overwhelming majority staining for IgG but not for kappa or lambda. A skeletal survey was negative for lytic lesions. The findings were felt to be consistent with a plasma cell dyscrasia associated gamma-heavy chain disease. The observed eosinophilia was felt to be reactive to the gamma-heavy chain disease as has been previously described.In the literature, gamma heavy chain disease is reported to most commonly present as a lymphoplasmacytic process and the finding of a plasma cell dyscrasia appears to be an unusual presentation of what is already a rare disease. We decided to tailor the treatment to the finding of a plasma cell dyscrasia. Therefore the patient was started on bortezomib 1. 3 mg/m2 SC D1, 4, 8, 11 and dexamethasone 20 mg PO D1, 2, 4, 5, 8, 9, 11, 12 of a 21 day cycle. His treatment was complicated by paroxysmal atrial tachycardia; a cardiac MRI did not reveal evidence of infiltrative cardiomyopathy. After 4 cycles of bortezomib and dexamethasone, the patient's total IgG had normalized at 1265 mg/dL and though a monoclonal gamma heavy chain was still detected by IFE of the serum and urine, a repeat bone marrow biopsy and aspiration was without morphologic evidence of the heavy chain plasma cell dyscrasia. The patient reported feeling subjectively improved with abatement of his malaise and fatigue and without further episodes of fever. Interestingly, the parameter that most seemed to correlate with his clinical status was eosinophilia which also decreased from a peak of 61% (absolute eosinophil count of 5063/uL) to 8–19% after 4 cycles with bortezomib and dexamethasone. Secondary eosinophilia has been reported in the literature in a subset of gamma HCD patients. The patient further underwent stem-cell mobilization in preparation for auto stem cell transplant with high dose Cytoxan, after which the eosinophilia completely resolved.There are only approximately 120 cases of gamma HCD described in the literature. To our knowledge, this is the first reported case of plasma cell dyscrasia associated gamma HCD responding to treatment with bortezomib and dexamethasone. Disclosures:No relevant conflicts of interest to declare.

A new form of myeloma “kidney”: shortened hemofilter survival and implications for membrane filtration plasmapheresis

Despite rigorous focus on extracorporeal CRRT parameters such as access, blood flow, hemoconcentration, and anticoagulation, some patients have unexpected repetitive hemofilter clotting. We instead explored patient or disease-related factors that could be responsible, and present a case of plasma cell dyscrasia in which paraproteins caused hollow fiber failure. A patient with IgG kappa chain multiple myeloma complicated by sepsis and acute renal failure was started on CVVH with a regional citrate anticoagulation protocol that typically yields filter life of >50 h. Polysulfone hemofilters repetitively clotted every 2-4 h, even after excluding circuit-related problems. Failed filters were examined by light, electron (EM), and immunofluorescence (IF) microscopy. Imaging of the hemofilters revealed several ultrastructural features typical for myeloma-associated alterations in native human tissue. Red cell rouleaux formation occurred within the hollow fibers. There was extensive protein layering on the luminal surface of the fibers with some extension into their walls: these deposits were IF+ for IgG kappa, and had a fibrillary substructure on EM. Extracorporeal hollow fiber phenomena recapitulate many intra-corporeal paraprotein effects such as those described in the kidney with plasma cell dyscrasias. Rapid protein layering suggests fouling of the membrane, decreased solute clearance before total device failure, and raises the theoretical concern that this might also occur during filtration plasmapheresis: we thus suggest serial serum free light chain levels to confirm their removal when using that technique. These findings emphasize the importance of disease rather than circuit-related factors that are under-appreciated causes of premature hemofilter failure.

The prolyl‐hydroxylase EGLN3 and not EGLN1 is inactivated by methylation in plasma cell neoplasia

EGLN1 and EGLN3 are members of the egg-laying-defective 9 (EglN) prolyl-hydroxylases which during normoxia catalyse hydroxylation of the hypoxia-inducible factor (HIF)-1alpha, thereby promoting its ubiquitination by a complex containing the von Hippel-Lindau (VHL) tumour suppressor. EGLN3 also has pro-apoptotic activity in some cell types. Analyses of a well-characterised series of cases of plasma cell dyscrasias, including multiple myeloma (MM), Waldenström's macroglobulinaemia (WM) and monoclonal gammopathy of undetermined significance (MGUS) surprisingly demonstrated that the CpG island of EGLN3, and not EGLN1, is frequently methylated in these disorders. Multiple myeloma patients with a methylated EGLN3 promoter showed trends towards an increased risk of death, bone lytic lesions, anaemia, advanced stage of disease and the presence of extramedullary disease. Those individuals with methylation in the EGLN3 CpG island also had significantly lower albumin levels. These data suggest that the prolyl-hydroxylases may be a novel class of potential tumour suppressors in plasma cell neoplasia that warrant further investigation with regard to their potential utility as biomarkers. Moreover, we observed that EGLN3 is also methylated at high frequency in B-cell lymphoma subtypes, implying that loss of EGLN3 is an important epigenetic event not only in plasma cell neoplasias but also in B-cell neoplasias.

Adverse Factors in Clinical Outcomes of T-Cell Large Granular Lymphocyte Leukemia.

Abstract 1086Poster Board I-108T-cell large granular lymphocyte (LGL) leukemia is a rare clonal lymphoproliferative disorder derived from cytotoxic T-lymphocytes (CTL) associated mostly with lineage-restricted cytopenias. While the clinical course is often indolent, some patients exhibit severe morbidities due to transfusion dependence, infections or thrombocytopenia. Intuitively, the level of the aberrant CTL clone as expressed by high LGL count or TCR Vβ clonal expansion by flow cytometry, the severity of neutropenia, pancytopenia, or the association with clonal myeloid disorders such as myelodysplastic syndromes (MDS) should herald a worse clinical outcome. Moreover, expression of CD56 has been established as an adverse marker for morbidity and mortality in number of hematological malignancies. In addition, rare cases of aggressive T-cell LGL leukemia were reported to display a CD3+/CD56+ immunophenotype.Based on the availability of a large, well characterized cohort of patients with T-cell LGL leukemia (n=86), we studied features associated with a poor clinical outcome and perceived need for aggressive therapy, including histomorphologic parameters, immunophenotype (CD56 expression). Both clinical response and overall survival (OS) were analyzed by means of categorical and survival statistical methods.The median patient age was 64 years (range, 15–80), and 55% were males. Rheumatoid arthritis was present in 14% of patients, 47% of patients had splenomegaly and 43% of those underwent splenectomy. Concomitant hematologic malignancies (5 cases of plasma cell dyscrasia, 8 with B-cell malignancies, and 3 with MDS/sAML) were found in 18% of patients, whereas solid cancers accounted for 15%. Neutropenia, anemia, and thrombocytopenia were seen in 63%, 50%, and 24%, respectively. Overall clinical response to a variety of therapies given was observed in 60% of patients. CD56 expression on the LGL clone was found in 15 patients (21%). Cases expressing CD56 were enriched among females (p=.005). CD56-positive cases were less likely to have neutropenia (p=.03) or thrombocytopenia (p=.03). In contrast to aggressive NK-cell lymphoma, the CD56 phenotype in T-cell LGL leukemia did not negatively impact OS (p=.85). However, increasing number of cytopenias (p=.006) were associated with poor survival. A dose-response pattern of association with OS was detected for pancytopenia (hazard ratio [HR]=9.9, p=.002) vs. bicytopenia (HR=4, p=.06) vs. single/none (reference) cytopenia. Similar results were obtained from logistic regression of factors associated with clinical response to therapeutic intervention. Neutropenia (p=.004) and thrombocytopenia (p=.02), but not anemia were associated with poorer clinical responses. All 5 patients with plasma cell dyscrasia had a complete response to the therapies targeting LGL (p=.01). Similarly, patients who underwent splenectomy tended to have a more favorable clinical response (p=.045).Multiple lineage cytopenias adversely affect both clinical outcomes and OS of T-cell LGL leukemia. In contrast to other diseases (T-cell acute lymphoblastic leukemia, AML, and multiple myeloma) a CD56+ immunophenotype was not associated with poor outcome in our cohort. Thus, as opposed to other studies, we would not suggest aggressive systemic chemotherapy in management of patients with T-cell LGL leukemia based purely on CD56 expression. DisclosuresNo relevant conflicts of interest to declare.

Activity of bortezomib (B) in plasma cell dyscrasia (PCD) with POEMS-like syndrome

e19564 Background: POEMS (polyneuropathy, organomegaly, endocrinopathy, m-protein, and skin changes) syndrome is a rare multi-system disorder associated with PCD. Although several reports revealed significant clinical benefit of IMIDs in POEMS syndrome cases that are not transplant candidates, no such published reports of B in this disease were found. Methods: We report the first case of PCD with POEMS like syndrome in addition to pulmonary hypertension, secondary right heart failure, and membranoproliferative glomerulonephritis that was successfully treated with single agent B. After presenting with the aforementioned signs and symptoms, a 64 year old white man, was diagnosed with PCD (bone marrow plasma cells 15%, IgG-λ, mild-moderate anemia, normal PET/CT, normal Cr and Ca) with ISS stage III. Due to being high risk for thromboembolic events, he was started on single agent B at 1.3mg/m2 days 1,4,8,11 Q21 days (cycles 1–4) which was reduced to 1.0mg/m2 days 1,4,8,11 Q21 days (cycles 5–6) due to grade 1 thrombocytopenia and neuropathy. This was followed by 3 maintenance cycles of 4 out of 5 weekly 1.0mg/m2. Results: Patient's breathing was subjectively better after cycle#1 despite experiencing side-effects from his pulmonary hypertension medications which had to be held and subsequently improved back to his baseline by cycle#4. By cycle#2, he was found to be in nCR with complete normalization of his bone marrow and serum electrophoresis by the end of therapy. He has been in nCR for almost 12 months so far. By cycle#3 his Raynaud's syndrome was significantly better with less dysesthesia which completely resolved by cycle#6. Conclusions: This case demonstrates for the first time the significant activity of B as a single agent in PCD with POEMS like syndrome. Further evaluation of the role of B as a first line agent in this disease, whether as single agent or in combination, is warranted. [Table: see text]

Polyneuropathyおよび内分泌症状を伴うplasma cell dyscrasiaの1例

Polyneuropathyおよび内分泌症状を伴うplasma cell dyscrasiaの1例

Plasma Cell Dyscrasia in Human Immunodefficiency Disease.

Plasmacytosis is commonly seen in the bone marrow biopsies of patients with acquired immunodefficiency disease AIDS and human HIV virus infection. Polyclonal increase of immunoglobulin is very common. However few cases of plasma cell dyscrasia are reported. The purpose of this abstract is to show our institution experience with plasma cell dyscrasia and HIV infection. For the last ten years ten patients were identified based on bone marrow biopsy, immunoelectophoresis and immunofixation, twenty four hours urine collection and urine electrophoresis and immunofixation. Immuno staining for kappa and lambda light chain to check for clonality were done on four cases. Mean age of patients is 49 years (range 33 to 59 years). Seven were black, two hispanic and one white. Nine were males and one female. All patients had plasmacytosis on bone marrow more than 30% and protiurea of more than one gram. five patients had nephrotic range protien urea. one patient had IgA lambda, one patient had Ig G kappa All patients had low CD4 counts except two patients with CD4 above 200 and have long standing HIV infection. One patient presented with hepatosplenomegally and increased IgM level and waldnestrome looking plasmacytoid lymphocytes. One patient had plasmablast and plasma cells syncitia who had rapidly fatal disease. one patient expired of respiratory failure before treatment. One patient, a female presented with plasma cell leukemia and did respond to Doxil, vincristine and dexamethasone therapy. She is alife. Two other patients with long standing HIV infection and CD4 count above 200 are still alife both patients were treated initially with Thalidomide and dexamethasone with excellent response. one of them failed Thalidomide after more than one year response and currently on his fourth cycle of velcaid (proteosome inhibitor). All patients were not on HIV therapy at time of diagnosis. In conclusion plasma cell dyscrasia with HIV infection do respond to treatment with durable response. Repetetive antigenic stimulation with HIV-1 p24 antigen are the proposed mechnism of oncogenesis.

Nephrotic syndrome in a patient with IgM myeloma with associated neutrophilia

An unusual case having IgM monoclonal gammopathy with clinical and pathologic features of multiple myeloma (MM) in association with neutrophilia and nephrotic syndrome is reported. The patient showed lytic bone lesions, decreased IgG and IgA levels, Bence-Jones proteinuria, nephrotic proteinuria with edema, and histological plasma cell infiltration typical of MM. Moreover, mature neutrophilic leukocytosis, hepatomegaly, high leukocyte alkaline phosphatase score (LAP), absence of Philadelphia (Ph) chromosome and bcr gene rearrangement were also evidenced, all these features representing findings typical of the recently described plasma cell dyscrasia-associated neutrophilia. After the diagnosis, the patient was treated with melphalan and prednisone, with an excellent response to the treatment. Different from the 30 cases so far reported, this is the first case of plasma-cell dyscrasia with associated neutrophilia due to IgM-producing monoclonal gammopathy. At the same time, this is the first reported case of nephrotic syndrome secondary to IgM myeloma.

Antigenic transformation in plasma cell dyscrasia

The WHO immunophenotype for plasma cell myeloma is deletion of CD19 and CD20, usual expression of CD38, CD138, and CD56, and occasional expression of CD10. Of the 39 cases of plasma cell dyscrasia in our study, the mean fluorescence intensities (MFI) of CD38, CD138, CD56, and CD19 were quantified in 30 cases. CD19 was absent in 38 of the cases (97.4%), whereas CD138 and CD38 were expressed in all 39 cases (100%). Most cases expressed CD38 and CD138 brightly with MFI values greater than 501, whereas all other marker expression was moderate with MFI greater than 301. Whereas CD38/CD56 dual expression was observed in 25 cases (64.1%), 14 failed to express CD56 (35.9%). CD56 expression was bright in 16 cases (53.3%), moderate in 2 cases (6.7%), and negative in the remaining 12 cases (40%) with MFI values of 200 or less. CD117 expression was positive in 9 of 24 cases (37.5%). In 32 of 39 cases, 27 were negative for CD20 (84.4%) and 28 were negative for CD10 (87.5%). Our results point to the value of quantitative fluorescence intensity in the flow cytometric evaluation of CD molecular expression or deletion in the diagnosis of hematopathologic disorders, such as plasma cell dyscrasia.

Deletion (20q) as the sole abnormality in Waldenström macroglobulinemia suggests distinct pathogenesis of 20q11 anomaly

The deletion of the long arm of chromosome 20, or del(20q), is a common cytogenetic abnormality in various myeloid disorders but is less commonly seen in lymphoid neoplasms. Here we report a case of Waldenström macroglobulinemia with del(20q) as the sole cytogenetic anomaly. No translocation including immunoglobulin genes was identified by spectral karyotyping (SKY) analysis. Reviewing all 11 reported cases of plasma cell dyscrasia possessing sole del(20q), including our case, none of 4 cases with del(20q) as an initial anomaly developed myelodysplastic syndrome–acute myeloid leukemia (MDS/AML), but at least 3 cases with del(20q) appearing after chemotherapy developed MDS/AML at or after the time of del(20q). We propose that the del(20q) may have different clinical significance in plasma cell dyscrasia: one is when del(20q) appears at diagnosis and may involve the initial event of oncogenesis, and the other is when del(20q) appears after treatment and is associated with therapy-related and potential MDS/AML risk.