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In the present research work, ultrasound-assisted synthesis of a series of novel azomethine derivatives of 1-phenylimidazo[1,5-a]pyridine has been achieved. The synthetic route involves the conversion of ethyl-1-phenylimidazo-[1,5-a]pyridine-3-carboxylate to 1-phenylimidazo[1,5-a]pyridine-3-carbohydrazide followed by nucleophilic addition-elimination reaction with diverse aromatic aldehydes. The developed clean and simple protocol offers a set of advantages such as mild reaction conditions, environment friendliness, and high atom economy apart from excellent yields (70–92%). All compounds were found to be stable in atmospheric conditions for a long period of time and were soluble in polar solvents. [ABSTRACT FROM AUTHOR]

Background: Female foeticide is the abortion of a female foetus outside of legal methods. Subsequent studies have provided evidence that it is excessive female mortality before birth; at birth, in infancy and childhood which mainly accounts for imbalance in sex ratio and missing of large number of female children in India. The Preconception and Prenatal Diagnostic Techniques (PCPNDT) Act was passed in 1994, making sex-selective abortion illegal. Objectives: i) To assess awareness about female foeticide, ii) To study knowledge, attitude and perception about female foeticide amongst adults of Kolhapur city. Material & methods: i) Study design - An observational - cross sectional, knowledge; attitude & perception study. ii) Tools used - Predesigned, pretested, structured questionnaire based survey in adults of Kolhapur city. iii) Study population -- Male & female Adults residing in defined study area of Kolhapur city during study period, iv) Statistical tests -- mean, percentage and other statistical analysis was conducted by using Microsoft- Excel. Results: Total 150 (85 females & 65 males) adults participated in this study. 142 subjects had knowledge about female foeticide. 81 felt son preference was main reason for female foeticide. Amongst participants, 95 heard about female foeticide prevention act. Conclusion: Results of study revealed that majority participants had knowledge about female foeticide but there was need to increase awareness regarding female foeticide prevention act. [ABSTRACT FROM AUTHOR]

Numerous illnesses can result in brief, asymptomatic syncopal episodes. Establishing ECG evidence of sinus node dysfunction/sick sinus syndrome is therefore essential before beginning treatment. Detailed laboratory findings in a 40 years old Female patient correlated with the clinical observation of cardiac rhythm disturbances in the sinus node, atria and atrioventricular (A-V) junction. Removal of a suppressive factor is necessary for the treatment of extrinsic causes of sinus node dysfunction. Full recovery was observed once metabolic parameters were eliminated. [ABSTRACT FROM AUTHOR]

Introduction: Symptoms of alcoholic peripheral neuropathy include impairments in sensory, motor, autonomic, and gait functioning that develop over a period of months. The primary and most common sign of alcoholic neuropathy is pain, either searing or dull. Materials and methods: The present study was conducted in the Department of Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, from August 2019 to September 2021. Total 100 chronic alcoholic heavy drinkers were chosen after a detailed history and clinical examination. The study protocol was reviewed by the concerned Ethical Committee and was granted ethical clearance. After explaining the purpose and details of the study, a written informed consent was obtained from the patients. Results: In our study the major autonomic symptoms reported by the patients were erectile dysfunction (27%), sweating disturbances (17%), postural giddiness (9%) and bladder disturbances (3%). In the autonomic function tests, H reflex was observed in 43%, Heart Rate Variability in 30% and Sympathetic Skin response in 27%. There was no association between the severity of alcoholic somatic neuropathy and the presence of autonomic neuropathy Conclusion: The present study concluded that a longer duration of alcohol use as well as increased age were shown to be related with a more severe type of peripheral neuropathy. Autonomic characteristics were seen in one-fourth of individuals with alcoholic neuropathic disease. In patients with alcoholic neuropathy, erectile dysfunction was the most prevalent autonomic symptom. In the case of alcoholic neuropathy, there was no evidence of a simultaneous involvement of somatic and autonomic fibres. [ABSTRACT FROM AUTHOR]

Acute Pancreatitis (AP) is a prevalent and rapidly progressive inflammatory disorder of the pancreas, often presenting with abdominal pain and elevated serum pancreatic enzymes. The present case report emphasises the crucial need for accurately diagnosing the underlying cause of Hypertriglyceridemic Pancreatitis (HTGP) in patients who present without any pre-existing co-morbidities. A 16-year-old female presented with a three-day history of generalised abdominal pain, vomiting and low-grade fever, with no comorbidities. Initial clinical assessment revealed signs of dehydration, tachypnoea, tachycardia and diffuse abdominal tenderness. Laboratory workups indicated a significant rise in amylase and lipase, hyperglycaemia, metabolic acidosis and pronounced Hypertriglyceridemia (HTG). Imaging studies corroborated the diagnosis of AP, revealing necrotic fluid collections. The patient was immediately started on plasmapheresis, aggressive intravenous fluid resuscitation, insulin infusion and supportive care, which included electrolyte correction, pain management and vigilant monitoring of vital signs. The autoantibody panel for type 1 diabetes, Antiglutamic Acid Decarboxylase antibodies (GAD) returned positive. Over the following days, the patient exhibited marked clinical improvement, with decreased abdominal tenderness, stabilisation of vital parameters and normalisation of biochemical abnormalities. Subsequent imaging confirmed the resolution of pancreatitis. Upon discharge, the patient was prescribed a regimen of insulin, statins, fenofibrate and saroglitazar for ongoing management of her lipid levels and diabetes. This case underscores that HTG may present as the first clinical manifestation of Type 1 Diabetes Mellitus. It also emphasises the critical importance of prompt and coordinated therapeutic interventions in managing HTGP, where early and effective treatment is crucial for optimising patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Acute ischemic stroke result of sudden impairement of the supply of blood to part of brain, and demonstrated commonly by focal neurological deficits.1 Acute Ischemic stroke constitute 85 to 87 percent of all the cases. Materials and methods: This was a Prospective Observational Study conducted at Dr. D.Y. Patil Medical College and hospital and Research Centre, Pimpri Pune. Subject diagnosed first time with stroke in the medicine OPD or Ward of a tertiary care hospital in the city of Pune were included in this study. Blood samples drawn in 24 to 72 hrs following stroke. Fibrinogen levels, hs-CRP levels, white blood cell counts, lipid profile and Erythrocyte Sedimentation Rate was calculated. Patients reviewed after four weeks following the time of the onset of stroke and compared using Glasgow Outcome Scale. Results : There was significantly high value for CRP among poor outcome group (P<0.05) but there was no much difference for mean value of age and Random Blood Sugar (RBS) for good and poor outcome groups (P>0.05). Among various risk factors found in study subjects only hypertension found significantly high level of Hs-CRP (p<0.05). Conclusion: Cerebral ischemia could provoke an acute response monitored by significant increase in levels of hs-CRP in AIS patients especially during early days of stroke. Study demonstrated that elevated levels of hs-CRP was prevalent in ischemic strokes. [ABSTRACT FROM AUTHOR]

Introduction: Globally stroke becomes important common cause of mortalities after coronary artery disease (CAD). It is the leading condition of chronic adult disability. Overall risk of stroke in a lifetime over the age of 55 is one in five for women and one in six for men. More than eighty percent of all strokes cases occur in developing nations. Material and methods: This was Prospective Observational Study carried out at Dr. D.Y. Patil Medical College and hospital and Research Centre, Pimpri Pune. Subject diagnosed first time with stroke in the medicine OPD or Ward of a tertiary care hospital in the city of Pune were included in this study. The sample size was estimated based on MRD data for last year admission rate for acute ischemic stroke in hospital. Results: Among various risk factors found in study subjects only hypertension found significantly high level of Hs-CRP (p<0.05). Conclusion: Cerebral ischemia could provoke an acute response monitored by significant increase in levels of hs-CRP in AIS patients especially during early days of stroke. [ABSTRACT FROM AUTHOR]

The His274→Tyr (H274Y) oseltamivir (Tamiflu) resistance mutation causes a substantial decrease in the total levels of surface-expressed neuraminidase protein and activity in early isolates of human seasonal H1N1 influenza, and in the swineorigin pandemic H1N1. In seasonal H1N1, H274Y only became widespread after the occurrence of secondary mutations that counteracted this decrease. H274Y is currently rare in pandemic H1N1, and it remains unclear whether secondary mutations exist that might similarly counteract the decreased neuraminidase surface expression associated with this resistance mutation in pandemic H1N1. Here we investigate the possibility of predicting such secondary mutations. We first test the ability of several computational approaches to retrospectively identify the secondary mutations that enhanced levels of surface-expressed neuraminidase protein and activity in seasonal H1N1 shortly before the emergence of oseltamivir resistance. We then use the most successful computational approach to predict a set of candidate secondary mutations to the pandemic H1N1 neuraminidase. We experimentally screen these mutations, and find that several of them do indeed partially counteract the decrease in neuraminidase surface expression caused by H274Y. Two of the secondary mutations together restore surface-expressed neuraminidase activity to wildtype levels, and also eliminate the very slight decrease in viral growth in tissue-culture caused by H274Y. Our work therefore demonstrates a combined computational-experimental approach for identifying mutations that enhance neuraminidase surface expression, and describes several specific mutations with the potential to be of relevance to the spread of oseltamivir resistance in pandemic H1N1. [ABSTRACT FROM AUTHOR]

In multiple myeloma, deletion of chromosome 13 (del(13)) is associated with poor prognosis regardless of treatment. This study analyzed the impact of del(13) status on response and survival following treatment with either bortezomib or high-dose dexamethasone in patients in the SUMMIT and APEX trials. Additionally, matched-pairs subset analyses were conducted of patients with and without del(13), balanced for age and International Staging System parameters. In both SUMMIT and APEX, prognosis appeared to be poorer in bortezomib-treated patients with del(13) compared with patients with no del(13) by metaphase cytogenetics. In the SUMMIT and APEX matched-pairs analysis, response and survival appeared comparable in bortezomib-treated patients with or without del(13) by metaphase cytogenetics. However, patients with del(13) receiving dexamethasone in APEX appeared to have markedly decreased survival compared with those without del(13) by metaphase cytogenetics. These matched-pairs analyses suggest that bortezomib may overcome some of the poor impact of del(13) as an independent prognostic factor. However, sample sizes were very small; these findings require confirmation from further studies.Leukemia (2007) 21, 151–157. doi:10.1038/sj.leu.2404442; published online 9 November 2006 [ABSTRACT FROM AUTHOR]

In a phase 2 open-label study of the novel proteasome inhibitor bortezomib, 54 patients with multiple myeloma who had relapsed after or were refractory to frontline therapy were randomized to receive intravenous 1·0 or 1·3 mg/m2 bortezomib twice weekly for 2 weeks, every 3 weeks for a maximum of eight cycles. Dexamethasone was permitted in patients with progressive or stable disease after two or four cycles respectively. Responses were determined using modified European Group for Blood and Marrow Transplantation criteria. The complete response (CR) + partial response (PR) rate for bortezomib alone was 30% [90% confidence interval (CI), 15·7–47·1] and 38% (90% CI, 22·6–56·4) in the 1·0 mg/m2 (8 of 27 patients) and 1·3 mg/m2 (10 of 26 patients) groups respectively. The CR + PR rate for patients who received bortezomib alone or in combination with dexamethasone was 37% and 50% for the 1·0 and 1·3 mg/m2 cohorts respectively. The most common grade 3 adverse events were thrombocytopenia (24%), neutropenia (17%), lymphopenia (11%) and peripheral neuropathy (9%). Grade 4 events were observed in 9% (five of 54 patients). Bortezomib alone or in combination with dexamethasone demonstrated therapeutic activity in patients with multiple myeloma who relapsed after frontline therapy. [ABSTRACT FROM AUTHOR]

Between 1985 and 1990, 133 patients with advanced multiple myeloma (MM) (74% resistance; 41% resistant relapse, RR) were treated with five high-dose therapy (HDT) regimens including: melphalan ≤100 mg/m² (MEL 100) (46 patients); MEL 100 plus GM-CSF (24 patients); MEL 140 plus autologous bone marrow transplantation (ABMT) (eight patients); MEL 140 plus TBI 850 cGy plus ABMT (37 patients); and thiotepa 750 mg/m² (THIO 750) + TBI 850 cGy plus ABMT (18 patients). The median follow-up of alive patients as of December 1997 was 9 years. Overall, 17% experienced treatment-related mortality within 60 days (TRM) and 12% achieved stringently defined complete remission (CR) with a median duration of 16 months; four of 16 patients (25%) remain in CR at 10 years. The median durations of event-free survival (EFS)/overall survival (OS) were 6/15 months. Superior EFS/OS were noted with MEL 100 plus GM-CSF and the two TBI-containing regimens (9/24 months among 79 patients) compared to the remaining 54 patients receiving MEL ≤100 or MEL 140 plus ABMT (3/5 months) (P = 0.0001/0.0001, respectively). Multivariate regression analyses (MVA) were performed so that, despite patient heterogeneity among the five treatment groups, potentially relevant disease, host, treatment, and supportive care variables could be identified that were associated with TRM, CR, EFS and OS. TRM was higher with creatinine >2.0 mg/dl, absence of ABMT/GM-CSF support and age >50 years; CR was superior with TBI-containing regimens and ≤12 months of prior therapy; EFS and OS both were longer with B2M ≤2.5 mg/l, age ≤50 years, absence of RR and with ABMT/GM-CSF support. In the presence of >2 favorable variables (32% of patients), median EFS/OS durations of 18/48 months were observed which progressively declined with 2 and <2... [ABSTRACT FROM AUTHOR]

This report summarizes 2 years experience in performing 336 autotransplant procedures in 251 consecutive patients with multiple myeloma, using high-dose melphalan at 200 mg/m2 in the context of a tandem transplant program. A total of 91 patients received 118 transplants as outpatients while the remaining 160 patients received 218 transplants as inpatients. Outpatients were more often younger, with better stem cell products, normal serum albumin and β-2-microglobulin levels as well as chemotherapy-sensitive disease compared to inpatients. There were no differences in hematopoietic recovery and non-hematologic toxicities between outpatient and inpatient transplant recipients. Post-transplant febrile neutropenia and most other post-transplant toxicities were managed successfully in an ambulatory setting. Although liberal criteria were developed for hospitalization of outpatients, including clinical parameters as well as patient desire and physician/nurse judgment, only 21% of outpatients required admission after transplantation. Median hospital stay for these outpatients was 9 days, while inpatients were hospitalized for a median of 15 days (P = 0.0001). After adjusting for differences in disease and host features, our study showed outpatient management resulted in significant financial savings due to lower pharmacy (42%), hospitalization (50%) and pathology/laboratory charges (36%). We conclude that outpatient transplants should facilitate access to myeloablative therapy, thereby improving complete remission rates and survival of myeloma patients. [ABSTRACT FROM AUTHOR]

This paper describes experimental procedures to relate multiaxial mechanical and ultrasonic responses of a cemented sand toward a study of stress-induced anisotropy due to microstructural changes under loading, unloading, and reloading. It is shown that the ultrasonic velocities and attenuation can provide indirect measures of microcracking and resulting induced anisotropy. The procedures proposed can lead to development of correlation between mechanical and ultrasonic characteristic and toward determination of material parameters based on laboratory and field measurements. [ABSTRACT FROM AUTHOR]

Investigates large volume leukapheresis (LVL) after mobilization with hematopoietic growth factors with or without high dose cyclophosphamide. Differential mobilization of hematopoietic progenitors and myeloma cells in patients with the diagnosis of multiple myeloma; Detection of myeloma cells in all peripheral blood stem cell products.

• Kabbe multi-component cyclocondensation. • Spiro[ chromane -2,4′- piperidine ]-4(3 H)-one functionalized building units. • Excellent docking profile. • Broad spectrum potent inhibitory activity against variety of pathogen. The spiro[ chromane -2,4′- piperidine ]-4(3 H)-one is an important pharmacophore. It is a structural component in many drugs, drug candidates (or lead compounds) and various biochemical reagents. This review demonstrated an impressive progress in syntheses of spiro[ chromane -2,4′- piperidine ]-4(3 H)-one-derived compoundsin the recent years and focuses on features of their biological relevance's. The prospects for the development of new biologically active substances containing a spiro[ chromane -2,4′- piperidine ]-4(3 H)-one pharmacophore are analyzed and briefly discussed in terms of its structure, reaction, mechanism, scope and potential utility. [ABSTRACT FROM AUTHOR]

Lymphomatoid granulomatosis (LYG) is a rare angiodestructive lymphoproliferative disorder (LPD) of uncertain etiology, with prominent pulmonary involvement. Recent studies indicate that LYG is an Epstein–Barr virus (EBV)-associated B cell LPD with large numbers of background reactive T lymphocytes (T cell-rich B cell lymphoma). Although the disease frequently, but not exclusively, occurs in various immunodeficiency states, it has not been reported in association with the transient immunosuppression following autologous bone marrow/peripheral stem cell transplantation (ABM/PSCT). We describe a patient who developed lymphomatoid granulomatosis of the lung approximately 2 weeks after high-dose chemotherapy and autologous peripheral stem cell transplantation for multiple myeloma. Although molecular studies showed no evidence of EBV genome in the biopsy material, the serologic profile with high IgM titers was suggestive of primary EBV infection. Complete radiologic remission occurred following reconstitution of the patient’s immune response after a 2-week course of ganciclovir treatment. Despite the apparently low frequency of LPD (both LYG and EBV-associated post-transplant lymphoma) in the ABMT setting, we believe that it should be considered in the differential diagnosis of patients whose clinical course following ABMT is complicated by fevers, in the absence of an identifiable infectious process. [ABSTRACT FROM AUTHOR]

The research article reports the synthesis and structural study of the optimized geometry of selenium (Se) bearing 24- and 28- membered macrocyclic Schiff bases, LaH2, LbH2 and their reactions with zinc metal ion. The reactions of the macrocyclic Schiff bases with ZnCl2 in 1:2 molar ratios result in the formation of bimetallic Zn(II) complexes having molecular composition [Se{(CH2)2N = CPh(4-CH3-C6H2O) PhC = O}2 · Zn2Cl2], (1) and [Se{(CH2)3N = CPh(4-CH3-C6H2O)PhC = O}2 · Zn2Cl2], (2). Moreover, as confirmed by various physico-chemical techniques such as elemental analysis, UV–Vis, FTIR,1H NMR, and mass spectrometry, the proligands underwent partial hydrolytic cleavage at one of the C = N positions and behave like hexadentate (N2O4) ligands binding to two Zn(II) ions via bridging through the Ophenolic atoms, which results in a square pyramidal geometry around Zn(II) with the chlorine atom occupying axial positions. Further, following density functional study, the stable optimized configuration of the Schiff bases LaH2 and LbH2 is found to adopt bowl shape geometry. Conversely, in molecular docking studies, the synthesized complex 1 exhibits a significantly stronger binding affinity (−8.7 kcal/mol) to the spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as compared to the common coronavirus disease 2019 (COVID-19) treatment drugs such as chloroquine, hydroxychloroquine, and remdesivir with activity percentage showing more than 20% overall effectiveness than remdesivir and thus indicating its potential for COVID-19 therapeutics. [ABSTRACT FROM AUTHOR]

Focuses on Neovastat, a naturally occurring extract that is derived from shark cartilage and used for the prevention of angiogenesis. Mechanism of action of Neovastat; Effects of Neovastat on angiogenesis, tumor growth and metastasis.

The article discusses the use of plasma exchange for the prevention of renal insufficiency or failure after autologous hematopoietic stem cell transplantation (AHSCT). It presents the cases of two patients with multiple myeloma who underwent the treatment and evaluates the usefulness of the preventative measure.

Background: The peroral transgastric endoscopic approach for intraabdominal procedures appears to be feasible, although multiple aspects of this approach remain unclear. This study aimed to measure intraperitoneal pressure in a porcine model during the peroral transgastric endoscopic approach, comparing an endoscopic on-demand insufflator/light source with a standard autoregulated laparoscopic insufflator.Methods: All experiments were performed with 50-kg female pigs under general anesthesia. A standard upper endoscope was advanced perorally through a gastric wall incision into the peritoneal cavity. The peritoneal cavity was insufflated with operating room air from an endoscopic light source/insufflator. Intraperitoneal pressure was measured by three routes: (1) through the endoscope biopsy channel, (2) through a 5-mm transabdominal laparoscopic port, and (3) through a 16-gauge Veress needle inserted into the peritoneal cavity through the anterior abdominal wall. The source of insufflation alternated between on-demand manual insufflation through the endoscopic light source/insufflator using room air and a standard autoregulated laparoscopic insufflator using carbon dioxide (CO(2)).Results: Six acute experiments were performed. Intraperitoneal pressure measurements showed good correlation regardless of measurement route and were independent of the type of insufflation gas, whether room air or CO(2). On-demand insufflation with the endoscopic light source/insufflator resulted in a wide variation in pressures (range, 4-32 mmHg; mean, 16.0 +/- 11.7). Intraabdominal pressures using a standard autoregulated laparoscopic insufflator demonstrated minimal fluctuation (range, 8-15 mmHg; mean, 11.0 +/- 2.2 mmHg) around a predetermined value.Conclusion: Use of an on-demand unregulated endoscopic light source/insufflator for translumenal surgery can cause large variation in intraperitoneal pressures and intraabdominal hypertension, leading to the risk of hemodynamic and respiratory compromise. Safety may favor well-controlled intraabdominal pressures achieved with a standard autoregulated laparoscopic insufflator. [ABSTRACT FROM AUTHOR]

Background: We have previously reported the feasibility of diagnostic and therapeutic peritoneoscopy including liver biopsy, gastrojejunostomy, and tubal ligation by an oral transgastric approach. We present results of per-oral transgastric splenectomy in a porcine model. The goal of this study was to determine the technical feasibility of per-oral transgastric splenectomy using a flexible endoscope.Methods: We performed acute experiments on 50-kg pigs. All animals were fed liquids for 3 days prior to procedure. The procedures were performed under general anesthesia with endotracheal intubation. The flexible endoscope was passed per orally into the stomach and puncture of the gastric wall was performed with a needle knife. The puncture was extended to create a 1.5-cm incision using a pull-type sphincterotome, and a double-channel endoscope was advanced into the peritoneal cavity. The peritoneal cavity was insufflated with air through the endoscope. The spleen was visualized. The splenic vessels were ligated with endoscopic loops and clips, and then mesentery was dissected using electrocautery.Results: Endoscopic splenectomy was performed on six pigs. There were no complications during gastric incision and entrance into the peritoneal cavity. Visualization of the spleen and other intraperitoneal organs was very good. Ligation of the splenic vessels and mobilization of the spleen were achieved using commercially available devices and endoscopic accessories.Conclusions: Transgastric endoscopic splenectomy in a porcine model appears technically feasible. Additional long-term survival experiments are planned. [ABSTRACT FROM AUTHOR]

Background: We have previously reported the feasibility of diagnostic and therapeutic peritoneoscopy including liver biopsy, gastrojejunostomy, and tubal ligation by an oral transgastric approach. We present results of per-oral transgastric splenectomy in a porcine model. The goal of this study was to determine the technical feasibility of per-oral transgastric splenectomy using a flexible endoscope. Methods: We performed acute experiments on 50-kg pigs. All animals were fed liquids for 3 days prior to procedure. The procedures were performed under general anesthesia with endotracheal intubation. The flexible endoscope was passed per orally into the stomach and puncture of the gastric wall was performed with a needle knife. The puncture was extended to create a 1.5-cm incision using a pull-type sphincterotome, and a double-channel endoscope was advanced into the peritoneal cavity. The peritoneal cavity was insufflated with air through the endoscope. The spleen was visualized. The splenic vessels were ligated with endoscopic loops and clips, and then mesentery was dissected using electrocautery. Results: Endoscopic splenectomy was performed on six pigs. There were no complications during gastric incision and entrance into the peritoneal cavity. Visualization of the spleen and other intraperitoneal organs was very good. Ligation of the splenic vessels and mobilization of the spleen were achieved using commercially available devices and endoscopic accessories. Conclusion: Transgastric endoscopic splenectomy in a porcine model appears technically feasible. Additional long-term survival experiments are planned. Laparoscopic procedures have many advantages over traditional surgery: they reduce the postoperative pain and risk of ventral hernias, shorten hospital stay and recovery period, and allow early return to regular physical activity [5–7, 15, 16]. We have previously reported the feasibility of transgastric diagnostic and therapeutic peritoneoscopy, including liver biopsy, gastrojejunostomy, and tubal ligation [10, 11, 13]. Here, we present results of transgastric splenectomy in a porcine model. [ABSTRACT FROM AUTHOR]

Summary:The unique antigenic determinants (idiotype (Id)) of the immunoglobulin secreted by myeloma tumor can serve as a tumor-specific antigen for active immunotherapy. Our objective was to induce tumor-specific T-cell immunity in bone marrow transplant (BMT) donors to enhance antitumor effects of allografts. We vaccinated five HLA-matched sibling donors with myeloma Id proteins isolated from recipient plasma before bone marrow harvest. Recipients were administered booster Id immunizations following transplantation. Vaccination induced donor Id and carrier-specific cellular and/or humoral immune responses. Two recipients died within 30 days of BMT from transplant-related complications. Id and carrier-specific T-cell responses were detected in all three remaining patients post-, but not pre-BMT and persisted for 18 months. All three surviving patients converted from partial to complete responses following BMT. Two of the three patients remain disease-free 7 years and 8 years after BMT, and the third died of renal failure after 5.5 years while in complete remission from myeloma. Our results suggest that myeloma Id vaccination induces specific T-cell immunity in healthy donors which may be transferable by BMT, is associated with prolonged disease-free survival of recipients, and may represent a general strategy to enhance graft-versus-tumor effect in other malignancies for which defined tumor-specific antigens exist.Bone Marrow Transplantation (2005) 36, 315–323. doi:10.1038/sj.bmt.1705057; published online 20 June 2005 [ABSTRACT FROM AUTHOR]

Objectives: To determine the progression-free survival at 12 weeks, to evaluate the toxic effects, and to analyze the biological activity of thalidomide in patients with relapsed multiple myeloma (MM) after high-dose chemotherapy and stem cell transplantation.Patients and Methods: From 1999 to 2001, we performed a multicenter prospective phase 2 study in patients with MM that relapsed after high-dose chemotherapy and stem cell transplantation to evaluate the efficacy of oral thalidomide, with dose escalation from 200 to 600 mg/d over 12 weeks and a subsequent maintenance phase of 200 mg/d for up to 1 year. Outcome was correlated with serum and plasma levels of vascular endothelial growth factor and serum levels of tumor necrosis factor alpha, soluble intercellular adhesion molecule 1, interferon gamma, interleukin (IL) 2, and IL-6 during treatment.Results: Thirty patients were treated (19 men and 11 women; median age, 58 years). The median number of prior therapies was 5, and the median duration from diagnosis of MM to study enrollment was 4.3 years. The 12-week progression-free survival rate was 67% (95% confidence interval [CI], 48%-86%). The observed response rate (partial response plus minor response) was 43% (95% CI, 28%-60%) with a median duration of 6 months. Attributable toxicities included constipation, fatigue, rash, and neuropathy, which was dose limiting in 8 patients (27%). Dose escalation from 200 to 600 mg/d was achieved in 50% of patients. Although responses were observed with lower doses, possibly eliminating the need to escalate the dose, responses were also seen in patients who completed the dose escalation. Some patients had disease progression while receiving the maintenance dose of 200 mg/d. Analysis of biomarker assays did not identify any biomarker associated with greater response, but a significant increase in levels of soluble intercellular adhesion molecule 1, IL-2, and interferon gamma was seen with thalidomide therapy.Conclusion: The optimal thalidomide dose varies, and adverse effects can be dose limiting. The dose of thalidomide therapy should be based on the individual patient to ensure that it is well tolerated and that a response is achieved. [ABSTRACT FROM AUTHOR]

Waldenström's macroglobulinaemia is a rare B-cell malignancy. It is prevalent in the sixth and seventh decades, the median age at diagnosis being 63 years. Conventional treatment has involved alkylator therapy, especially chlorambucil given daily at a low dose or intermittently at a higher dose. Purine analogues, used initially as salvage therapy in refractory disease, are increasingly used for initial therapy. However, purine analogue therapy entails significant complications, including immunosuppression, pancytopenia and autoimmune haemolysis. Moreover, it is unclear whether purine analogues extend survival. All of these need to be considered before initiation of therapy. More recently, anti-CD20 monoclonal antibody and thalidomide have been used with a 30% response in treated patients. High-dose therapy with stem cell support achieves a partial response in a majority of patients receiving this modality of therapy. The median survival of 5 years has not improved considerably since the introduction of purine analogues. Complete response is still uncommon; using all available modalities of therapy may increase the complete response rate and improve survival. Great strides in understanding the malignant cell, the microenvironment and the potential interactions have identified potential targets for therapy in multiple myeloma. These agents may also be useful in Waldenström's macroglobulinaemia. Since this is a rare malignancy, all patients should be treated with well-designed clinical protocols to achieve improvement in outcome. [ABSTRACT FROM AUTHOR]

Forty-two patients allografted for multiple myeloma after not having attained at least a partial remission (n = 19) or after having experienced disease progression (n = 23) following one autograft were compared with 42 pair-matched controls who underwent salvage autotransplantation under identical conditions. Autografted controls were matched closely for albumin, C-reactive protein, creatinine, disease sensitivity, duration of standard therapy prior to the first transplant, Ig isotype, karyotype, LDH, and response to the first transplant, but, in comparison to allografted patients, were older, had higher Β2-microglobulin, and had a shorter interval between the two transplants. The complete remission rate was 41% after allogeneic and 33% after autologous transplantation (P = NS). The 3-year probability of event-free survival was comparable for the two groups (25 ± 8% after autografting and 20 ± 8% after allografting). The 3-year probability of survival was significantly higher after autologous transplantation (54 ± 8% vs 29 ± 9%; P = 0.01). Twenty-one patients in the autograft group were alive 11-59 months (median 32) following the second transplant, while 15 patients in the allograft group were alive at 10-53 months (median 20). The 3-year probability of disease progression was significantly lower after allogeneic transplantation (31 ± 10% vs 72 ± 9%, P = 0.03). The 1-year probability of transplant-related mortality was significantly higher after allografting (43 ± 8% vs 10 ± 5%; P= 0.0001). We conclude that while autografting appears to be superior to allografting for salvage therapy of myeloma persisting or relapsing after one previous autotransplant in terms of overall survival, event-free... [ABSTRACT FROM AUTHOR]

Eighteen extensively pre-treated patients (35–73 years, median 46) with relapsed multiple myeloma received salvage chemotherapy with 6 g/m2 cyclophosphamide, 800 mg/m2 carboplatin, and 1800 mg/m2 etoposide (CCV) as a 96-h continuous infusion followed by autologous peripheral blood stem cells. The median number of prior chemotherapy regimens was five (range 4–10), including at least one autograft. Four patients died of toxicity, and one developed dialysis-dependent renal failure, while the others tolerated CCV well. Three of six patients with pre-transplant creatinine of >1 mg/dl died of toxicity compared with one of 12 with creatinine 1 mg/dl (P = 0.083, Fisher’s exact test). Three of four patients treated with four previous regimens showed >50% reduction in tumor compared with one of 14 treated with >4 regimens (P = 0.02, Fisher’s exact test). At the last follow-up, five patients were alive at 8–24 months (median 13) with stable (n = 1) or progressive (n = 4) disease, and nine had died of progressive disease at 2.5–15 months (median 7). We conclude that CCV chemotherapy with autografting is tolerated well by extensively pre-treated myeloma patients provided the pre-transplant creatinine is normal, but toxicity in patients with abnormal renal function is high. The efficacy in multiply relapsed disease is poor, with response in only 22% of patients. CCV may deserve further evaluation early in the course of myeloma in patients with normal renal function. [ABSTRACT FROM AUTHOR]

Background: Very little is known about the risk that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection poses to cancer patients, many of whom are immune compromised causing them to be more susceptible to a host of infections. As a precautionary measure, many clinical studies halted enrollment during the initial surge of the global Novel Coronavirus Disease (COVID-19) pandemic. In this case report, we detail the successful treatment of a relapsed and refractory multiple myeloma (MM) patient treated with an anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy immediately following clinical recovery from COVID-19. Case presentation: The 57 year old Caucasian male patient had a 4-year history of MM and was considered penta-refractory upon presentation for CAR T cell therapy. He had a history of immunosuppression and received one dose of lymphodepleting chemotherapy (LDC) the day prior to COVID-19 diagnosis; this patient was able to mount a substantial immune response against the SARS-CoV-2 virus, and antiviral antibodies remain detectable 2 months after receiving anti-BCMA CAR T cell therapy. The recent SARS-CoV-2 infection in this patient did not exacerbate CAR T-associated cytokine release syndrome (CRS) and conversely the CAR T cell therapy did not result in COVID-19-related complications. One month after CAR T cell infusion, the patient was assessed to have an unconfirmed partial response per International Myeloma Working Group (IMWG) criteria. Conclusion: Our case adds important context around treatment choice for MM patients in the era of COVID-19 and whether CAR T therapy can be administered to patients who have recovered from COVID-19. As the COVID-19 global pandemic continues, the decision of whether to proceed with CAR T cell therapy will require extensive discussion weighing the potential risks and benefits of therapy. This case suggests that it is possible to successfully complete anti-BCMA CAR T cell therapy after recovery from COVID-19. CRB-402 study registered 6 September 2017 at clinicaltrials.gov (NCT03274219). [ABSTRACT FROM AUTHOR]

Data from 225 multiple myeloma (MM) patients, undergoing peripheral stem cell (PBSC) mobilization with high-dose cyclophosphamide and hematopoietic growth factors, were analyzed for median CD34+ cell count and median time to post-transplant neutrophil (ANC > 500/μ l) and platelet (> 50 000/μ l) recovery according to age groups (20–49, 50–59 and 60 years) and duration of prior therapy (12, 13–24 or >24 months). Fifty-seven of the 225 patients were 60 years. No difference in either the median number of CD34+ cells collected or time to engraftment occurred between age groups, when adjusted for duration of prior therapy. These data support the concept that autotransplants can be performed safely in patients 60 years and that these patients should not be excluded from the most effective treatment modalities. [ABSTRACT FROM AUTHOR]

RT is an important therapeutic modality utilized at various stages along the treatment continuum in MM. However, there has been no national study of RT utilization and data on the factors that influence use are lacking due to its palliative nature and the fact that RT can be used multiple times over the course of MM treatment. The Connect® MM Registry is a largely community-based registry that provides a unique opportunity to evaluate real-world use and factors that influence RT use in MM treatment. The Connect MM Registry is a large, US, multicenter, prospective observational cohort study of patients (pts) aged ≥ 18 y with newly diagnosed MM from 250 community, academic, and government sites. This analysis investigated Registry pts who received RT. RT utilization was captured quarterly over the entire course of pt treatment, in the first 6 months from study enrollment and in the last 6 months prior to death. Data from 9/28/2009 — 2/4/2021 were used in this analysis. The Connect MM Registry included 3011 pts of whom 903 (30%) received RT at any time. Twenty-one percent (636/3011) received RT within the first 6 months of study enrollment and 16% (241/1526) within the last 6 months before death (among all death pts). Overall, pts were predominantly white (83%), male (57%), with a median age of 67 y (range 24 – 94) and received a triplet anti-MM regimen (55%). At baseline, most common indications for RT were pain (65%), impending fracture (13%), or neurologic compression (12%). On multivariable analysis, overall RT use was significantly less common in pts with Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 – 1 vs 2+ (odds ratio [OR], 0.58; P = 0.0014) and more common in ISS stage I + II vs III pts (OR, 1.61; P = 0.0009). We observed no statistically significant difference regarding pt age, sex, race/ethnicity, insurance status, geographic region, intent to transplant, or use of novel anti-MM agents in first line of treatment. In the first 6 months after study enrollment, there was more than double the odds of RT use in pts with ISS I+II vs III (OR, 2.07; P < 0.001) and in pts with ECOG PS 0–1 vs 2+ (OR, 0.46; P < 0.001). No other sociodemographic or clinical factors studied were significant. In the 6 months before death, the only factor associated with increased RT use was increasing lines of MM therapy (OR, 1.19; P < 0.001). These results from the CONNECT MM Registry, representative of real-world practice, show that even in the era of novel anti-MM agents, RT is used frequently for pt care. RT use is dictated by clinical factors, including PS and disease stage, rather than sociodemographic factors. Earlier in MM diagnosis, RT may be used as an adjunct to palliate symptoms (poor PS) or to delay systemic therapy (early stage). Toward the end of life, RT is more frequently used for palliation, with limited systemic options after multiple lines of therapy. [ABSTRACT FROM AUTHOR]

Change in tumor size estimated using longitudinal tumor growth inhibition (TGI) modeling is an early predictive biomarker of clinical outcomes for multiple cancer types. We present the application of TGI modeling for subjects with multiple myeloma (MM). Longitudinal time course changes in M-protein data from relapsed and/or refractory MM subjects who received single-agent carfilzomib in phase II studies ( n = 456) were fit to a TGI model. The tumor growth rate estimate was similar to that of other anti-myeloma agents, indicating that the model is robust and treatment-independent. An overall survival model was subsequently developed, which showed that early change in tumor size (ECTS) at week 4, Eastern Cooperative Oncology Group performance status (ECOG PS), hemoglobin, sex, percent bone marrow cell involvement, and number of prior regimens were significant independent predictors for overall survival ( P < 0.001). ECTS based on M-protein modeling could be an early biomarker for survival in MM following exposure to single-agent carfilzomib. [ABSTRACT FROM AUTHOR]

Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T0). The median age at diagnosis was 58 years, and time from diagnosis to T0 was 3.3 years. Following T0, 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (44%) including partial response in 69 (32%). The median overall survival and event-free survival from T0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs. [ABSTRACT FROM AUTHOR]

Multiple myeloma is the most common indication for high-dose chemotherapy with autologous stem cell support (ASCT) in North America today. Stem cell procurement for ASCT has most commonly been performed with stem cell mobilization using colony-stimulating factors with or without prior chemotherapy. The target CD34+ cell dose to be collected as well as the number of apheresis performed varies throughout the country, but a minimum of 2 million CD34+ cells/kg has been traditionally used for the support of one cycle of high-dose therapy. With the advent of plerixafor (AMD3100) (a novel stem cell mobilization agent), it is pertinent to review the current status of stem cell mobilization for myeloma as well as the role of autologous stem cell transplantation in this disease. On June 1, 2008, a panel of experts was convened by the International Myeloma Foundation to address issues regarding stem cell mobilization and autologous transplantation in myeloma in the context of new therapies. The panel was asked to discuss a variety of issues regarding stem cell collection and transplantation in myeloma especially with the arrival of plerixafor. Herein, is a summary of their deliberations and conclusions. [ABSTRACT FROM AUTHOR]

The serum immunoglobulin-free light chain (FLC) assay measures levels of free κ and λ immunoglobulin light chains. There are three major indications for the FLC assay in the evaluation and management of multiple myeloma and related plasma cell disorders (PCD). In the context of screening, the serum FLC assay in combination with serum protein electrophoresis (PEL) and immunofixation yields high sensitivity, and negates the need for 24-h urine studies for diagnoses other than light chain amyloidosis (AL). Second, the baseline FLC measurement is of major prognostic value in virtually every PCD. Third, the FLC assay allows for quantitative monitoring of patients with oligosecretory PCD, including AL, oligosecretory myeloma and nearly two-thirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial FLC measurements outperform PEL and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial FLC measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using FLC assay in place of 24-h urine PEL for monitoring or for serial measurements in PCD with measurable disease by serum or urine PEL. This paper provides consensus guidelines for the use of this important assay, in the diagnosis and management of clonal PCD.Leukemia (2009) 23, 215–224; doi:10.1038/leu.2008.307; published online 20 November 2008 [ABSTRACT FROM AUTHOR]

The article focuses on the role of vertebral augmentation in the treatment of multiple myeloma. The study shows that vertebral augmentation is most likely to benefit those myeloma patients with mechanical pain and can be used for both acute and chronic fractures. However, it is not recommended for asymptomatic fractures unless there is documented increased collapse and deformity progression. A consensus statement from the International Myeloma Working Group is also presented.

Summary:The role of autologous stem cell transplantation (AuSCT) in older multiple myeloma patients is unclear. Using data from the Autologous Blood and Marrow Transplant Registry, we compared the outcome of 110 patients ?the age of 60 (median 63; range 60-73) years, undergoing AuSCT with that of 382 patients <60 (median 52; range 30-59) years. The two groups were similar except that older patients had a higher ß2-microglobulin level at diagnosis (P=0.016) and fewer had lytic lesions (P=0.007). Day 100 mortality was 6% (95% confidence interval 4-9) and 1-year treatment-related mortality (TRM) was 9% (6-13) in patients <60 years, compared with 5% (2-10) and 8% (4-14), respectively, in patients ?60 years. The relapse rate, progression-free survival (PFS) and overall survival (OS) in the two groups were also similar. Multivariate analysis of all patients identified only an interval from diagnosis to AuSCT >12 months and the use of two prior chemotherapy regimens within 6 months of AuSCT as adverse prognostic factors. Our results indicate that AuSCT can be safely performed in selected older patients: the best results were observed in patients undergoing AuSCT relatively early in their disease course.Bone Marrow Transplantation (2003) 32, 1135-1143. doi:10.1038/sj.bmt.1704288 [ABSTRACT FROM AUTHOR]

Haematopoietic growth factors, especially granulocyte colony-stimulating factor (G-CSF), are frequently utilized alone for peripheral blood stem cell (PBSC) procurement to avoid the morbidity associated with high-dose chemotherapy (HDT). Moreover, the cytotoxic agents used may not be the most optimal therapy for the malignancy. It also makes scheduling of apheresis easier. Factors having an impact on PBSC procurement and engraftment after HDT were analysed in 117 multiple myeloma patients mobilized with G-CSF (10–16 µg/kg, median 12 µg/kg) alone using Cox regression analysis. A median of 6·2 × 106 CD34 cells/kg (range 0·6–34·1) were procured during leukapheresis and a median of 2·5 × 106 CD34 cells was infused after the first HDT (range 0·3–23·9). The only factor significantly affecting optimal PBSC procurement was duration of preceding conventional chemotherapy (P = 0·002). Granulocyte recovery was prompt in almost all patients, 75% of whom attained a granulocyte count of 0·5 × 109/l by day 13 (median 11, range 7–19). However, platelet recovery to both 20 × 109/l (median 12 d, range 8–50+) and 50 × 109/l (median 20 d, range 7–205+) varied widely. On univariate analysis, factors influencing platelet recovery were the number of CD34 cells/kg infused, age, β2-microglobulin levels, response to preceding therapy, bone marrow plasmacytosis and duration of prior therapy. Factors attaining significance on multivariate analysis included number of CD34 cells/kg infused (P = 0·007), β2-microglobulin levels (P = 0·0001), most probably representing disease load, and age (P = 0·002). Patients with high tumour burden, i.e. β2-microglobulin levels > 2·5 mg/l, probably benefit from chemotherapy for mobilization both in terms of... [ABSTRACT FROM AUTHOR]

The role of more intense conditioning for second transplant was evaluated in myeloma patients achieving at least partial remission (PR) after first transplant with melphalan at 200 mg/m2. Forty-three patients received more intensive conditioning for the second transplant. Nineteen patients received cyclophosphamide 120 mg/kg along with melphalan 200 g/m2 (MEL-CY; group 1) while 24 patients received total body irradiation (1125 cGy) in conjunction with melphalan 140 mg/m2 (MEL-TBI; group 2). Forty-three matched control patients were identified from 450 patients receiving melphalan alone for second transplant (MEL200; group 3). Engraftment and toxicities were comparable among the groups with the exception of increased treatment-related mortality of 8% in group 2 compared to none in groups 1 and 3 (P = 0.07). Despite identical CR rates of 74, 71 and 70%, respectively, in groups 1, 2 and 3 (P = 1.0), event-free survival (median: 27, 15 and 61; P < 0.0001) and overall survival (median: 39, 25 and 76 months; P = 0.003) were significantly decreased in patients receiving more intensive conditioning (groups 1 and 2). Lymphocyte recovery, evaluated as a surrogate for immune recovery, was inferior in more intensively treated patients (groups 1 and 2 compared to group 3). Our findings suggest that more intense conditioning appears to have no benefit in patients responding to their first cycle of high-dose therapy and may even be detrimental in this setting. Bone Marrow Transplantation (2000) 25, 483–487. [ABSTRACT FROM AUTHOR]

The net impact of malignancy and anti-tumor therapy on bone resorption in myeloma is poorly understood because conventional skeletal radiographs are relatively insensitive for the diagnosis and monitoring of bone disease. We performed determinations of bone mineral density (BMD) at the lumbar spine, femoral neck and radial diaphysis by dual energy X ray absorptiometry (DEXA) in 168 consecutive patients with myeloma seen at our institution. Follow up studies were performed in 41 of these patients. A detailed analysis of patient and disease characteristics was performed to identify the determinants of BMD. Compared to normal age and sex matched controls, mean (± SE) BMD was significantly decreased at the lumbar spine (Z score −0.4 ± 0.10) and femoral neck (Z score −1.0 ± 0, 10), but was surprisingly above normal at the radial diaphysis (Z score + 0.35 ± 0.10), a cortical bone site devoid of hematopoietic marrow, suggesting a differential bone preserving effect at this site. Lack of correlation between the BMD findings and the presence or extent of radiographically evident osteolytic lesions suggested the presence of a systemic bone disease. On multivariate analysis, duration of disease >12 months (p = 0.003) and female sex (p = 0.01) were independently associated with a lower BMD at the femoral neck/lumbar spine. On follow up DEXA (n = 41), BMD increased at ≥ 1 site in 9 of 20 patients receiving bisphosphonates and in only 2 of 21 patients not receiving such therapy (p = 0.02). Similarly a decline in BMD at ≥ 1 site was seen in 9 of 21 patients not receiving bisphosphonates, irrespective of the disease response status. Interval pamidronate therapy (p = 0.0007) and a low serum beta-2-microglobulin (< 2.5 mg/l) (p = 0.04) were the two most significant variables associated with an increase in BMD on multivariate analysis. These data suggest that myeloma is associated with a systemic bone disease with progressive... [ABSTRACT FROM AUTHOR]

Standard doses of alkylating agents or purine analogues effect response rates of up to 50% in Waldenström's macroglobulinaemia (WM); however, complete responses are infrequent and there are no cures. We have evaluated the feasibility, safety and efficacy of high-dose chemotherapy with peripheral blood stem cell support in six patients aged 45–69 years (median 51.5) with WM; four patients relapsed after prior therapy inclusive of purine analogues and two patients proceeded with transplant after minimal therapy. Four patients mobilized adequate numbers of stem cells; however, two patients with more extensive fludarabine therapy failed to mobilize and required a second attempt at stem cell collection. Five patients were treated with melphalan 200 mg/m2, including one patient who received tandem transplants and one patient who received melphalan 140 mg/m2 with added total body irradiation (TBI). There was no treatment-related mortality and non-haematological toxicities were manageable. Engraftment was prompt except in one patient with extensive prior use of fludarabine. All the six patients achieved at least partial response (PR), including one who achieved complete response (CR). Five patients are alive and four are event-free at 52+, 15+, 12+ and 2+ months post transplant. This pilot study suggests safety and efficacy of high-dose therapy in WM and suggests that the peripheral blood stem cells should preferably be procured prior to extensive use of purine analogues. [ABSTRACT FROM AUTHOR]

The Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) was developed as a disease-specific, patient-reported outcome measure for the assessment of health-related quality of life (HRQoL) in patients with MM, as part of the FACT measurement system. The FACT-MM combines the General version of the FACT (FACT-G) with a MM-specific subscale (14 items). While minimal clinically important differences (MCID) have been established for other FACT scales, there is no known, validated definition of MCID for the FACT-MM. [Extracted from the article]

Despite significant advances in therapy, prognosis for patients with multiple myeloma (MM) remains relatively poor, with a highly refractory disease course. MCID analyses demonstrated that most patients did not experience decline in the early cycles of treatment; this pattern was consistent with MCID defined either as 10% of the instrument range (Ringash 2007), or as an ECOG-based anchor. [Extracted from the article]

A response by P. G. Richardson, J. F. San Miguel, S. Lonial, D. Reece, A. Jakubowiak, and M. Hussein to a letter to the editor regarding their article "The Research Mission in Myeloma" in the previous issue is presented.