bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of CD126 (IL-R alpha) on Plasma Cells in Monoclonal Gammopathies.
Authors: Mahmood Syed T. , Kumar Shaji , Kimlinger Teresa K. , Haug Jessica L. , Timm Michael , Wellik Linda , Kline Michael , Rajkumar S. Vincent 
Published: April 2020

Abstract
Background: IL-6 is important for proliferation and inhibition of apoptosis in malignant plasma cells. Understanding the role of IL-6 receptor alpha chain (CD126) in the pathogenesis of plasma cell disorders may help in developing future treatment therapies for these diseases. A previous study has shown that CD126 (alpha subunit of IL-6 receptor) is expressed distinctly in myeloma, monoclonal gammopathy of unknown significance (MGUS), and plasmacytomas when compared to normal. We performed this study in order to confirm and describe the expression of CD126 in different plasma cell disorders.
Design and Methods: Using flow cytometry we assessed CD126 expression on clonal plasma cells from patients with Primary Amyloidosis (n=7), monoclonal gammopathy of undetermined significance (MGUS) (n=13), smoldering Myeloma (SMM) (n=19) and active Myeloma (n=22), as well as normal plasma cells (n=9). Plasma cells were identified by their characteristic CD38/45 expression. The expression of CD126 was separately analyzed on the CD45 positive and negative plasma cells. CD 126 expression was considered significant when more than 20% of the cells had expression.
Results: CD126 expression was seen distinctly in plasma cell disorder plasma cells and not in normal plasma cells when all plasma cells were studied together. The highest expression percentages were found in Amyloid (28%) followed closely by MGUS 29(%), then SMM (23%), and Myeloma (12%) cells. The CD45 neg subset was similarly positive in the plasma cell disorder group. In this group, MGUS showed the highest expression percentage followed distantly by Amyloid, Myeloma, and SMM. The CD45 pos subset was uniformly positive in expression of CD126. If was found that this subset expressed higher levels of CD126 in all the studied plasma cell disorders and normal plasma cells when compared to the CD45 neg subset.
Conclusion: The findings of this study confirm the increased expression of CD126 in plasma cell disorders when compared to normal plasma cells. The higher expression of CD126 in the CD45 pos plasma cell subset has not been previously described. In addition, the CD45 pos subset expressed higher levels of CD126 in all study groups when compared to the CD45 pos subset. This data contributes to the understanding of IL-6 receptor physiology and confirms the important role of the CD45 pos subset in the proliferation of neoplastic plasma cells. The findings are in accordance with the increased proliferative rates seen in the CD45 fraction of malignant plasma cells.
Unusual Presentation of IgD Lambda Multiple Myeloma with Femoral Head Amyloidosis: A Case Report and Literature Review.
Authors: Pu Jeffrey J. , Yoe Joseph 
Published: April 2020

Abstract
IgD Multiple Myeloma accounts only for 2% of all Multiple Myeloma cases. It has been associated with various conditions and with complications involving many organs. The prognosis for IgD Multiple Myeloma is poor. This case report describes how a patient was diagnosed as IgD Lambda Multiple Myeloma complicated with left femoral head Amyloidosis. Initially, this 71 years old male patient presented with worsening left hip pain, reduced appetite, and weight loss for six months. Laboratory data showed chronic anemia, hypercalcemia, and acute renal failure. Bone marrow biopsy demonstrated sheets of plasma cells with abnormal nuclei. The initial routine serum immunofixation did not show any elevation of Immunoglobulins; and instead, noted decreased immunoglobulin level. Because of this unusual pattern of low Ig G, A, and M level, further work up on IgD investigation was pursued. Serum IgD workup showed a peak of 71 mg/dl and the urine immunofixation also demonstrated large amount of free monoclonal Lambda light chain. Finally, a left total hip arthroplasty was done. Congo Red stain of left femoral head biopsy revealed amyloidosis. This case illustrates association of IgD myeloma with amyloidosis. At the same time, it could easily be misdiagnosed as light chain disease if IgD abnormality was not carefully considered as a differential diagnosis. In addition, a concise review on IgD Multiple Myeloma is given.
Multiple Lung Nodules and a Pancreatic Mass at the Initial Presentation of Multiple Myeloma: A Rare Case.
Authors: Aribandi Lavanya , Makary Adel Z. 
Published: April 2020

Abstract
Extramedullary tumors are a rare manifestation of multiple myeloma. Approximately half of these are present at initial diagnosis and the rest occur during the course of the disease. Pancreas is rarely involved by multiple myeloma and the diagnosis is often made postmortem. Lung lesions are also rarely encountered. We present a rare case of multiple myeloma with asymptomatic extraosseous soft tissue lesions in the form of multiple lung nodules and a pancreatic mass at the initial presentation. Despite his multiple extraosseous lesions, he responded well to chemotherapy and radiation therapy with resolution of pulmonary nodules, pancreatic mass and orbital mass.
Response to Bortezomib in Combination after Relapse o Non-Response to First Treatment with Bortezomib Alone in Myeloma Multiple Patients.
Authors: Rubio-Martinez Araceli , Recasens Valle , Delgado Pilar , Garcia-Zueco Juan Carlos , Rubio-Felix Daniel , Giraldo Pilar 
Published: April 2020

Abstract
Background: Bortezomib has been shown to be effective in multiple myeloma (MM), but there is a limited experience in response to re-treatment.
Aims: To evaluate the efficacy of Bortezomib in refractory/relapsed MM.
Patients and methods: 41 patients treated with Bortezomib (1,3 mg/m2 on days 1,4,8,11 in a 21-day cycle) in second or more line as clinical practice protocol were included. The response was evaluated according EGBMT criteria (Bladé J, Samson D, Reece E et al). Patients that no have reached response after 4 courses or relapsed after CR or PR received a combination of: bortezomib+dexamethasone (group BD) or bortezomib+melphalan+prednisone (group BMP). Adverse effects were registered.
Results: 39 valuable patients (males 43.0%). Mean age 59.9 years (34–82), over 65 years (66.6%). Bortezomib was administered in second line: 10 (25.6%), in third or more: 29 (74.3%). Overall Response: 76.4%: (CR+PR 70.5%, MR 5.9%), (CR 41.1%/CR-IFE negative 14.7%), Mean courses to reached response: 4.7. No relation to response and presence or not chromosomal aberrations. At 32 months on follow-up 9 patients had dead (26.4%) and 15 (44.1%) maintained response without therapy. In 17 patients (43.5%), a combination of BD (10 patients) or BMP (7 patients) were administrated by relapse or progression. Responses: group BD 6 PR, 3 NR; 1NV group BM P 3 PR, 3 NR, 1NV. Adverse events: thrombocytopenia 38.4 (grade III: 17.9), fatigue 38.5%, peripheral neuropathy 33.3, constipation 35.8%, diarrhea 20.5%, ZHV 12.8%, infection 33.3, pyrexia 10.2%, hypotension 5.1%, grade 3 leucopenia 12.8%. In 3 patients (7.6%) the therapy was disrupted by toxicity. We haven’t found any differences in adverse events in patients treated with bortezomib in combination.
Conclusions: Related to the synergism of Bortezomib in combination, the re-treatment induces response (60%) in refractory MM without severe adverse effects. In spite of the scarce follow-up some patients could be benefit in re-treatment with Bortezomib. It is necessary to explore more combinations and to know the results of clinical trials. When there is not response after the 4th course of Bortezomib it is recommendable to use in combination
Use of Immunoglobulin Infusions in the Management of Bortezomib-Induced Peripheral Neuropathy in Multiple Myeloma.
Authors: Teoh Gerrard , Tan Daryl , Hwang William , Koh Liang Piu , Chuah Charles , Ng Heng Joo 
Published: April 2020

Abstract
Bortezomib (VELCADE) is a novel proteasome inhibitor that has shown tremendous clinical efficacy in Asian patients with multiple myeloma (MM). Prior studies have found that about a third (35%) of Caucasian patients develop bortezomib-induced peripheral neuropathy (PNY); and 12% and 5% of these patients require dose-reduction or discontinuation of bortezomib, respectively. Moreover, it has anecdotally been reported that a greater proportion of Asian patients receiving bortezomib develop PNY, and we are concerned that this unwanted effect of bortezomib would greatly limit the use of a drug that would otherwise be highly-effective for Asian MM patients. We therefore analyzed 20 Asian patients with MM who were treated with bortezomib, and found that up to 75% (15 out of 20) of patients developed bortezomib-induced PNY - sensory (75%) and/or motor (50%); confirming the observation that Asian patients are more prone to developing bortezomib-induced PNY. The majority of sensory PNY were mild. Grades 1 or 2 sensory PNY was seen in 45%, grade 3 in 15%, and grade 4 in another 15% of patients. Of these, 80% of patients reported painful neuropathies - 53% requiring dose reduction, and 27% requiring discontinuation of bortezomib. By contrast, motor PNY was more severe - 5% of patients reported grades 1 or 2, 15% with grade 3, and 30% with grade 4 motor PNY. In other words, if PNY develops in an Asian patient with MM, it is more likely to be a mild painful sensory PNY. However, if motor PNY occurs, it is more likely to be severe. For the treatment of PNY, all patients received gabapentin (600 mg to 1,400 mg per day), and 9 patients received L-carnitine (2 or 3 tablets a day). Gabapentin-treated patients reported only minimal effectiveness of this drug in relieving their symptoms, whereas no objective improvements were observed in all L-carnitine-treated patients. Similarly, amitriptyline was given to 3 patients with severe painful PNY and only a non-sustained modest improvement was reported in all these patients. In contrast, improvements of at least 1 grade in both symptoms and function were reported by all 9 patients who received intravenous immunoglobulins (IVIG). In the most significant of these, a patient who was bed-ridden because of grade 4 combined sensorimortor PNY, dramatically recovered (became pain-free, and improved to grade 2 motor weakness) within 2 days of completing IVIG 2.0 gm/kg divided over 4 days. In conclusion, Asian MM patients have indeed significantly higher rates of bortezomib-induced PNY, which unfortunately often leads to dose-reduction and/or discontinuation of bortezomib. Our data demonstrate that IVIG may be a useful agent for the management of these patients; and for facilitating the continued administration of bortezomib.
Bevacizumab Therapy for POEMS Syndrome.
Authors: Ramasamy Karthik , Lang Stephen , Chapell Jackie , Schey Stephen 
Published: April 2020

Abstract
41 yr old male presented with pain and weakness of upper and lower limbs. He was bed bound with ECOG score 4. Investigations confirmed the diagnosis of POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes) syndrome. He had typical features including glomerular hemangiomas on the skin, mild hepatosplenomegaly, sensorimotor polyneuropathy, IgG lambda paraprotein 3.3g/l, elevated FSH, LH and TSH. A course of cyclophosphamide and dexamethasone was given with no clinical response. He was also given a trial of plasma exchange and parenteral Immunoglobulins. Symptoms plateaued and he was followed up with rehabilitation support. He re-presented 18 months later with widespread low-grade lymphadenopathy, stable paraprotein, ascites, poor appetite and weight loss. Lymph node biopsy showed Castleman’s disease like changes along with osteosclerotic lesions in pelvis and raised CSF protein of 3.13g/l with rest of CSF analysis being normal. Bone marrow trephine showed paratrabecular deposits of lambda light chain restricted CD38 positive plasma cells. Ascitic fluid was sterile consistent with a transudate. Vascular endothelial growth factor (VEGF) level prior to treatment was elevated at 4587 pg/ml (Normal: 72–704 pg/ml). Large volume abdominal paracentesis ranging between 2–3 litres of clear fluid was performed weekly. In view of the raised VEGF, 4 doses of Bevacizumab (anti-VEGF) 2.5mg/kg were administered as an intravenous infusion over one hour fortnightly. VEGF level normalised after first dose of bevacizumab (131.2 pg/ml) and remained normal prior to the fourth dose (136.5 pg/ml). There were no infusional reactions or haematologic adverse effects. Frequency of paracentesis decreased to three weekly, his appetite and performance status improved with ECOG score 2. 3 weeks after the fourth dose he was readmitted with tense ascites, pleural effusion, diarrhoea, pyrexia and severe abdominal pain. Meropenem resistant pseudomonas was grown from ascitic fluid. After therapeutic paracentesis and antibiotics a Leveen shunt from abdomen to right internal jugular vein was performed to prevent reaccumulation. Despite shunting, he reaccumulated fluid in the third space and developed respiratory and pre renal failure and succumbed to it. At post mortem there were non-specific changes in the lungs and heart with no evidence of pulmonary embolism or bowel perforation and Leveen shunt remained patent. Bevacizumab promptly reduced VEGF levels with significant reduction in pleural and peripheral effusion with subjective improvement in neurological status. Bevacizumab appears to induce clinical response in a proportion of patients with POEMS syndrome. We suggest that a Phase I study should be considered to identify dose, duration of therapy and safety of Bevacizumab.
Final Results of a Prospective, Non-Interventional Study on Bortezomib (Velcade®, VEL) in the Treatment of Multiple Myeloma (MM) in Office-Based Hematology Units (OBH).
Authors: Knauf Wolfgang Ulrich , Otremba Burkhard , Overkamp Friedrich , Bammer Susanne , Angermund Ralf 
Published: April 2020

Abstract
Objectives
This study was performed to investigate efficacy and tolerability of VEL under routine conditions in patients (pts.) with MM, who have received at least 1 previous line of therapy and are refractory to or have relapsed after their last therapy.
Methods
Pts. were treated up to 24 weeks with the recommended dose of VEL (1.3 mg/m2 day 1, 4, 8, 11 q3weeks). Any further diagnostic and therapeutic instructions were not provided in the protocol. At baseline, demographical and medical history data were collected, including type and number of preceding therapies and concomitant diseases. Adverse events (AEs) were continuously documented. Final data analysis is presented here.
Results
A total of n=50 pts. (27 female, 23 male) were included in 14 German OBHs. Median age was 68 years (yrs.), whereby 19 pts. were &gt; 70 yrs. old. A median of 1295 days (d) (range: 49–6201 d) passed between initial diagnosis and start of VEL therapy. Pts. had received a median of 2 prior treatments.
Most frequently reported concomitant diseases were hypertension in 36.0% of the pts., renal failure in 28.0% and coronary heart disease in 14.0%, as well as heart failure in 8.0%. Overall, 10.0% of the pts. exhibited a PNP at the start of therapy (6.0% grade 1 without pain; 4.0% without indication of the degree of severity).
Up to now assessment of response is available in 39/50 pts., with 2 CR, 22 PR, 7 MR, 6 SD and 2 PD. The overall response rate (CR+PR+MR) was 79,4%. Time to best response (CR+PR+MR) was median 3 cycles (range 1–7), while in 3 pts. best response was achieved after 1 cycle.
At end of study, a total of 458 AEs were documented (9.6% classified grade 3; 2.6% grade 4). The investigators assessed 242 AEs (52.8%) as related to VEL and most frequently documented: thrombocytopenia (18.2%), anemia (16.9%), leukocytopenia (9.9%), neuropathy/paresthesia (9.1%), vomiting/nausea (6.6%), asthenia (5.0%) and diarrhea (4.1%).
A total of 34/458 AEs (5.5%) were classified as serious, with 14 (41.2%) of them related to the VEL therapy according to the investigator’s opinion. 2 pts. (4.0 %) died in the course of the trial (deaths not related to VEL). Safety data are under ongoing assessment.
Conclusion
VEL therapy in an unselected, pretreated group of MM pts. is effective and well tolerated. Findings of this non-interventional study confirm efficacy and safety results of large randomized clinical trials. Thus the use of VEL is also suitable under routine conditions in office-based hematology units.
Thalidomide and Dexamethasone in Newly Diagnosed Multiple Myeloma.
Authors: McHugh Johnny , O’Ceallaigh Cathal , Keane Colm , Otridge Brian W. , O’Gorman Peter 
Published: April 2020

Abstract
PURPOSE: The combination of thalidomide and dexamethasone has been shown to have excellent antimyeloma activity in both relapsed and newly diagnosed patients. This combination offers a potential oral, less toxic alternative to standard regimens. This single-centre retrospective study evaluates the activity of the combination of thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma attending the haematology department of the Mater Misericordiae University Hospital, Dublin.
METHODS: Forty-six patients with newly diagnosed multiple myeloma between April 2000 and April 2006 were treated with thalidomide and dexamethasone as first line treatment. The median age of the patients was 70 years (range 46 to 88 years). The median serum paraprotein level was 32g/l (range 2 to 99g/l). The median bone marrow plasma cell percentage was 40% (range 10% to 99%) The first twenty-two patients were commenced on thalidomide at 200mg od with the dose increased by 200mg every two weeks if tolerated to a maximum of 800mg od. The most recent twenty-four patients were commenced on thalidomide at 100mg od with the dose increased to a maximum of 200mg if tolerated. All patients received dexamethasone 40mg per day on days 1–4, 9–12 and 17–20 ot the first cycle and for a four day pulse every four weeks for subsequent cycles.
RESULTS: The response rate was 67.4% when assessed by Blade criteria (50% reduction in serum myeloma protein and 90% reduction of urine myeloma protein on at least two occasions for a minimum of 6 weeks). A complete response was observed in 10.9% of patients. There was no significant difference in response rates between the higher thalidomide dose group and the lower thalidomide dose group. The main toxicities included constipation in 57.8%, hyperglycaemia in 33.3%, peripheral neuropathy in 22.2%, drowsiness in 15.6%, peripheral oedema in 15.6%, venous thromboembolism in 11.1%, rash in 11.1% and proximal myopathy in 8.9%. Routine anticoagulation was not used although patients with additional risk factors for venous thromboembolism received prophylactic dose low molecular weight heparin and in total 53.3% of patients were receiving either aspirin, warfarin or low molecular weight heparin at the time of treatment. There was no significant difference between the two thalidomide dose groups in terms of frequency of toxicities. However 27.3% of patients in the higher thalidomide dose group had their treatment stopped within one month due to toxicities compared to 4.2% in the lower dose group.
CONCLUSION: The combination of thalidomide and dexamethasone is safe and effective in the treatment of newly diagnosed multiple myeloma. There is less treatment-limiting toxicity and no loss of efficacy with lower doses of thalidomide.
Efficacy of Rituximab in Anti-MAG Neuropathy.
Authors: Singh Jaswinder , Malani Ashok , Festoff Barry , Kambhampati Suman 
Published: April 2020

Abstract
Background: The majority of cases of peripheral neuropathy related to monoclonal gamopathy of unknown significance (MGUS) are of the IgM type. Neuropathy associated with antibodies to myelin-associated-glycoprotein (anti-MAG) accounts for 50% of IgM-related neuropathies. Anti-MAG related neuropathies often improve after treatment with human Ig (IVIG), or a combination of cyclophosphamide (cytoxan) and plasma exchange. But this improvement is often short-lived, expensive, and the repeated doses of cytoxan may predispose patients to an increased risk of infections and secondary malignancies. Therefore, efficacious and less toxic treatment approaches are needed in anti-MAG-related neuropathies. We postulated that Rituximab treatment would eradicate the autoantibody producing B-cell lymphocyte clone in patients with IgM antibody-related neuropathies and thereby reduce the titers of neurotoxic antibodies.
Methods: Two patients followed at the Kansas City Veterans Affair Medical Center neuromuscular clinic with diagnoses of MGUS and IgM antibody-related neuropathies were evaluated by history, physical examination, electrodiagnostic evaluation, and serum testing. Both patients had sensory-motor (mixed) neuropathies characterized by slowly progressive asymmetric weakness, muscle wasting, areflexia, and sensory loss. These patients also had elevated anti-MAG titers and were previously treated with plasma exchange, Cytoxan, IVIG, resulting in a good clinical improvement of their symptoms. The clinical remissions, however, were short lived (3–6 moths). Both the patients were then treated with four weekly IV infusions of Rituximab (375 mg/M2).
Results: During the ensuing 12 months after Rituximab treatment, both patients had subjective and objective sensory and motor neurological improvement, however, the degree of improvement was variable. We noticed no change in the titers of anti-MAG levels despite clinical improvement. Based on our experience we postulate that the clinical improvement may not correlate with changes in the anti-MAG titers. Moreover, it could be possible that the recovery of anti-MAG titers may lag behind the clinical improvement. Results for both the patients are formulated below in the table. The graph depicts the anti-MAG titers and physical strength of one of the treated patient in relationship to the Rituximab treatment.
Conclusion: Rituximab is a relatively safe and efficacious therapy for patients with IgM antibody-directed polyneuropathies. Additional large scale, prospective studies with a longer follow-up are needed to develop Rituximab as a targeted therapy against anti-MAG neuropathies.
Response to Rituximab Response to Rituximab