scholarly journals Preliminary Exploration of the Stimulating Effect of Pomalidomide on BCMA-CART in the Treatment of Multiple Myeloma Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4846-4846
Author(s):  
Yuelu Guo ◽  
Kai Hu
Keyword(s):  
Multiple Myeloma ◽  
Cell Expansion ◽  
Remission Rate ◽  
Early Stage ◽  
Gamma Interferon ◽  
Hematopoietic Stem ◽  
Soluble Cd25 ◽  
Number Of Patients ◽  
Tnf Α ◽  
Before And After

Abstract Research Background: BCMA-CART treatment can give patients with relapsed and refractory multiple myeloma a chance of remission, but because the patient's own lymphocytes are poor in number and function, poor autologous CART cell expansion or failure to expand will affect the efficacy of CART. It is necessary to explore ways to improve the curative effect of CART so as to increase the remission rate. Research purposes The purpose of the study was to observe the changes in symptoms, signs, and vital signs of patients with pomalidomide in the early stage after BCMA-CART reinfusion, analyze the changes in cytokines and CART expansion after oral pomalidomide, and summarize the symptoms of such patients Disease remission rate and survival status. Research methods Collect the clinical characteristics of patients who took pomalidomide orally within one month after BCMA-CART cell reinfusion in our hospital from January 2019 to July 2021, and count the symptoms and signs of patients with pomalidomide before and after CART. Compare the values of cytokine and CART cell expansion before and after CART reinfusion to explore the synergistic effect of pomalidomide with CART. Research result From January 2019 to July 2021, a total of 5 patients with multiple myeloma who took pomalidomide orally within 1 month after BCMA-CART cell reinfusion were treated in our department from January 2019 to July 2021. There were 2 male patients and 3 female patients. The median age is 63 years (35-70). The median number of patients' previous treatment lines is 7 (3-18), of which 3 patients(3/5) have had previous autologous hematopoietic stem cell transplantation. The number of reinfused BCMA-CART cells in 5 patients was 8.13 (0.11-16.5)*105/kg, the median time of oral pomalidomide was 14 (8-19) days of CART reinfusion, and the dose was 1 case (1/ 5) 4 mg 1/day for patients, 2 mg 1/day for 3 patients (3/5), 1 mg 1/5 for 1 patient (1/5); 3 patients (3/5) before pomalidomide treatment ). The number of CART cell expansion in patients was 0.00%, 0.40% in 1 case (1/5), and 7.03% in 1 case (1/5). None of them had fever. 4 patients (4/5) had fever after taking pomalidomide, the median maximum body temperature was 38.95 (38.3-40.2) ℃, and the fever occurred 1.5 (1-4) days after taking pomalidomide; The amplification of CART cells of all patients can be detected by PCR method after pomalidomide, and the start time of amplification is 5 (2-8) days after taking pomalidomide; the amplification of CART cells The highest peak occurred at 9 (4-19) days after taking pomalidomide. The peak of CART cell expansion increased by 3.86 (0.06-37.8)% compared to before treatment with pomalidomide; the CRS classification after taking pomalidomide of 4 cases (4/5) were grade 2 and 1 case (1/5) was grade 3, of which 2 cases (2/5) had ICANS. Cytokines were increased in all patients after pomalidomide. Among them, IL-6 of all cases (5/5) increased after pomalidomide, and the highest value of IL-6 appeared after pomalidomide. At 9 (5-22) days after pomalidomide administration, the increase value was 20.60 (16.16-380.23) pg/mL; among the 4 patients that can be counted, TNF-α level of 4 patients (4/4) were increased after pomalidomide administration, the highest value of TNF-α appeared at 7.5 (6-8) days after pomalidomide administration, and the increase value was 21.825 (11.60-32.81) pg/mL. All 4 countable patients had higher soluble CD25 after pomalidomide administration, and the highest value of soluble CD25 appeared 11 (6-14) days after pomalidomide administration, and the value of increase was 7987 (3765-26173) pg/Ml. Gamma interferon of all 4 countable patients increased after pomalidomide administration, and the highest value of gamma interferon appeared in 9.5 (2-14) days after pomalidomide use, the increase value was 18.49 (5.3-587.8) pg/ml. The efficacy of 5 patients evaluated after 1 month after BCMA-CART was 2 cases (2/5) with stable disease, 2 cases (2/5) with partial remission, and 1 case (2/5) with disease progression. As of the deadline for submission, 5 patients are currently alive, and the median OS is 113 (42-236) days after CART reinfusion. Analysis conclusion Pomalidomide can promote the expansion and activation of CART and stimulate the release of cytokines in the early stage after BCMA-CART treatment. Whether it can enhance the anti-tumor effect of CART remains to be further studied. Disclosures No relevant conflicts of interest to declare.

Hypocalcemia during Autologous Stem Cell Transplant with Concurrent Biphosphonate Use in Patients with Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4335-4335
Author(s):  
Kitsada Wudhikarn ◽  
Gregory M. Vercellotti ◽  
Mukta Arora
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Serum Calcium ◽  
Plasma Cells ◽  
Remission Rate ◽  
Calcium Supplementation ◽  
Normal Serum ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Autologous Hsct

Abstract Autologous hematopoietic stem cell transplantation (HSCT) is one of the treatment options which has been shown to enhance remission rate and survival in patients with multiple myeloma. Biphosphonates are used in conjunction with standard therapy and can ameliorate and prevent bony complications, i.e. bone pain, hypercalcemia or fracture, via direct inhibition of osteoclasts and possible anti-tumor effects on malignant plasma cells. With more frequent use of biphosphonates, there are increasing reports of noticeable adverse effects such as osteonecrosis of the mandible, renal failure and hypocalcemia. In this study we report three patients with multiple myeloma who received autologous HSCT accompanied with monthly administration of bisphosphonates and developed significant hypocalcemia post HSCT. All three patients had normal serum calcium levels at diagnosis and prior to transplant. The maximum drop in serum calcium was noted four to ten days post HSCT, and corrected by five to 13 days post HSCT. All three patients received biphosphonates eight to 20 days prior to the episode of hypocalcemia. All patients noted resolution of hypocalcemia with oral and intravenous calcium supplementation over three to ten days. Two patients required ongoing oral calcium supplementation for approximately one month after resolution of hypocalcemia. Multiple potential mechanisms can be postulated for the hypocalcemia in these patients undergoing HSCT such as chronic nutritional deficiency, GI losses, renal losses, vitamin D deficiency in addition to bisphosphonate use. Potentially melphalan, IV fluids, and furosemide may also play roles. Osteoclasts, bone marrow stromal cells and myeloma cells all can modulate calcium levels directly or indirectly through cytokine production. Future laboratory and clinical studies will focus on biochemical marker of complication and attention is needed while using bisphosphonates during autologous HSCT in myeloma patients.

Comparison of Autologous and Allogeneic Transplantation As Therapy of First Relapse in Patients with Multiple Myeloma - Long-Term Follow up Analysis,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4124-4124
Author(s):  
Ute Hegenbart ◽  
Stefan O Schonland ◽  
Axel Benner ◽  
Christina Wunder ◽  
Thomas M. Moehler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Chronic Gvhd ◽  
High Dose ◽  
Two Stage ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
First Relapse ◽  
First Diagnosis

Abstract Abstract 4124 BACKGROUND: Most patients (pts) undergoing high-dose therapy with melphalan 200 mg/m2 (HDM) and autologous transplant for multiple myeloma (MM) develop disease recurrence. The optimal salvage treatment including autologous (auto-) and allogeneic (allo-) hematopoietic stem cell transplantation (SCT) as consolidation therapy for these patients is not yet defined. METHODS: We performed a retrospective analysis of 116 pts with MM treated in our institution between 1999 and 2005. Inclusion criteria were relapse after auto-SCT (n=88) or failure of induction treatment (n=28) and age ≤ 65 years. Re-induction was performed with TCED (thalidomide, cyclophosphamide, etoposide and dexamethasone (Möhler et al, Blood 2001). Seventy-one pts (median age, 59 yrs) received auto-SCT (auto-group) after HDM followed by maintenance therapy with thalidomide or interferon-alpha in 42 pts. Forty-five pts (allo-group, median age, 53 yrs) underwent a reduced-intensity allo-SCT (related in 24 pts), mostly using conditioning with 2 Gy total body irradiation and fludarabine. Thirty-eight pts received an auto-allo-tandem-SCT (Maloney, Blood 2003) and 7 pts have been directly transplanted after TCED. Statistical analysis was done using the two-stage test of Qiu & Sheng (JRSS Ser. B 2008) to compare two possibly crossing survival curves. Extended Cox proportional hazards regression models were applied to allow for time-varying differences between the two SCT groups. RESULTS: Estimated median follow-up after start of TCED was 95 months. All pts received a median number of 3 TCED cycles for re-induction therapy. 64 of 116 pts (55%) showed at least a PR after TCED chemotherapy (CR in 3 pts). TRM was 17% after 2 years in the allo-group and differed significantly from the auto-group (3%, p=0.02). More CR were achieved after allo-SCT compared to auto-SCT (17 vs. 4 pts., p<0.001). Median overall survival (OS) was 26 months for the auto group and 23 months for the allo group (Figure 1, p=0.16). Median progression-free survival (PFS) was 12 months for both groups but crossing hazards were observed (Figure 2, p=0.03, two-stage test of Qiu & Sheng). The results of multivariate regression analysis for OS and PFS including age at relapse-SCT, response to TCED, time between first diagnosis until first relapse-SCT and primary progression are shown in table 1. In the allo group, there was no OS or PFS difference between related and unrelated donors (multivariate analysis). Cumulative incidence of chronic GvHD was 73% (53% extensive). Patients with chronic GvHD showed a better OS and PFS than pts without (univariate analysis, both p<0.01). CONCLUSIONS: To our knowledge, this is the first analysis in a large number of patients with a long follow-up comparing allo with auto SCT in 1st myeloma relapse which were treated uniformly with TCED therapy for re-induction. Main problem was MM recurrence. However, younger pts with disease response after TCED and longer time from first diagnosis to first SCT after relapse profit best from TCED and this transplant approach. Most interestingly, disease control is better after allo compared to auto SCT in univariate and multivariate analysis leading to a PFS of about 20% after 4 years. In our opinion, allo SCT is a valuable clinical option for patients with 1st relapse after HDM and auto SCT. Disclosures: No relevant conflicts of interest to declare.

Graft-Versus-Host Disease Following Myeloablative Busulfan Plus Fludarabine and Busulfan Plus Cyclophosphamide For Allogeneic Hematopoietic Stem Cell Transplantation In Acute Myeloid Leukemia In First Complete Remission

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3290-3290
Author(s):  
Qifa Liu ◽  
Hui Liu ◽  
Daihong Liu ◽  
Yongrong Lai ◽  
Jing Sun ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Tnf Α ◽  
Before And After ◽  
First Complete Remission

Abstract Background Results from single institutions had shown that compared with busulfan plus cyclophosphamide (BuCy) conditioning, limiting tissue damage by myeloablative busulfan plus fludarabine (BuFlu) conditioning might decrease cytokines release, leading a lower incidence of the graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In our prospective, multicenter and parallel-group study, further comparison was made of the incidences and severities of GVHD following BuCy and BuFlu myeloablative conditioning regimens in patients undergoing allo-HSCT for AML in first complete remission (CR1), and analyzed plasma cytokines before and after the conditioning. Methods A total of 148 patients with AML-CR1 undergoing allo-HSCT were enrolled into BuCy (busulfan1.6mg/kg, iv q12 hours, -7 ∼ -4d; cyclophosphamide 60 mg/kg.d, -3 ∼ -2d) or BuFlu (busulfan 1.6 mg/kg, iv q12 hours, -5 ∼ -2d; fludarabine 30 mg/m2.d, -6 ∼ -2d) group between January 2007 and January 2013. For patients enrolled between January 2012 and January 2013, plasma concentrations of IL-6, IL-1β, TNF-α, CXCL-10 and IL-17A before and after conditioning were measured by Enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. Regimen-related toxicity (RRT), incidences and severities of acute and chronic GVHD, and overall survival were compared between the two groups. Results Of the 148 patients enrolled in the study, the data of 142 cases were used to determine the endpoints in the intent-to-treat population (72 in BuFlu group and 76 in BuCy group). The levels of TNF-α and IL-6 were significantly higher after the conditioning (5.60±4.40 vs 8.94±5.50 and 2.19±1.24 vs 6.06±12.16 pg/ml, P <0.001 and P =0.045 ), however, there were no significant differences on these cytokines between the two groups. The levels of CXCL-10 in BuCy group was significantly higher than that in BuFlu group (P =0.012). The incidence of I-II° and III-IV° acute GVHD were 42.1% and 6.8%, and 36.1% and 5.7%, respectively, in BuCy and BuFlu group (P=0.363 and P=0.770, respectively). Chronic GVHD occurred in 29 of 69 (41.7%) and 30 of 72 (41.7%) patients, respectively, in BuCy and BuFlu group (P= 1.000). And the incidence of extensive chronic GVHD were 14.3% and 16.7%, respectively, in BuCy and BuFlu group (P= 0.670). The median follow up duration was 824 (range, 3–2345) days. The 5 year overall survival were 79.2 ± 4.4% and 78.6 ± 76.1% (P= 0.555), respectively in BuCy and BuFlu group Conclusion In this report, the incidences and severities of acute GVHD as well as chronic GVHD were similar between BuFlu and BuCy regimen in AML-CR1 patients undergoing allo-HSCT. Disclosures: Liu: National Natural Science Foundation of China (Grant No.81000231, No.81270647) and Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding; It was supported by 863 Program (No. 2011AA020105), National Public Health Grand Research Foundation (Grant No. 201202017): Research Funding.

scholarly journals Bortezomib-Based Regimens for Newly Diagnosed Multiple Myeloma in China: A Report of 12-Year Real-World Data

2020 ◽  
Vol 11 ◽  
Author(s):  
Jingsong He ◽  
Donghua He ◽  
Xiaoyan Han ◽  
Gaofeng Zheng ◽  
Guoqing Wei ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Treatment Regimen ◽  
Remission Rate ◽  
Progression Free Survival ◽  
Treatment Quality ◽  
Real World Data ◽  
Free Survival ◽  
Treatment Regimens ◽  
Before And After

Background: Improve the treatment quality might affect patients’ efficacy and survival.Methods: Five hundred thirty multiple myeloma patients treated in four hematological centers in China from February 2006 to August 2018 were enrolled. General characteristics, treatment regimens and cycles, efficacy, survival and adverse events of the patients treated before and after August 2013 (later refer to as the before-2013 and after-2013 group) were analyzed and compared.Results: The results suggested that patients who received optimized treatment regimen and route of administration completed more cycles of treatment in the after-2013 group. Although the overall response rate was similar between the two groups (88.6 vs. 90.5%), patients in the after-2013 group had higher complete remission rate (39.1 vs. 28.6%) and better progression-free survival. Subgroup analysis suggested that patients aged 65 years and older, with non-high-risk D-S, ISS, and R-ISS stages, had a significant benefit in progression-free survival.Conclusion: Therefore, in clinical practice in China, by reducing the economic burden brought by the treatment on patients and optimizing the treatment regimen, more patients can be treated with better regimens in a prolonged duration to achieve better efficacy and survival, especially in elderly and non-high-risk patients.

scholarly journals Oral changes in patients before and after transplantation of solid organs and hematopoietic stem cells

2020 ◽  
pp. 106-106
Author(s):  
Olivera Jovicic ◽  
Jelena Mandic ◽  
Zoran Mandinic ◽  
Aleksandra Colovic
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Oral Epithelium ◽  
Solid Organ ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Dental Tissues ◽  
Number Of Patients ◽  
Gingival Enlargement ◽  
Before And After

Introduction/Objective. The aim of this paper is to point out the prevalence and severity of oral diseases in patients in the period before and after the transplantation of solid organs and hematopoietic stem cells. Methods. MEDLINE literature search was done via PubMed. Results. The development and improvement of transplantation medicine in specialized centers lead to an increasing number of patients, both adults and children, with transplanted solid organs and hematopoietic stem cells. Despite the success of therapy, numerous changes and complications can be observed on other organs in patients undergoing transplantation of solid organs and hematopoietic stem cells in the pre and post-transplant phase. Systemic diseases and conditions related to organ and cell transplantation, which are accompanied by numerous oral manifestations. The most common oral changes are gingival enlargement, desquamation of the oral epithelium, very painful ulcerations, polypoid and granulomatous changes in the oral mucosa, hard dental tissues with frequent complications, developmental anomalies of teeth in younger children, and in the later stage also the occurrence of oral cancer. After transplantation of solid organs and hematopoietic changes in the oral cavity and other organs occur depending on the patient?s post- transplantation period as well as on the applied immunosuppressive therapy. Conclusion. Oral changes development pre and post transplantation of solid organ and hematopoietic stem cells points to the importance of timely and good cooperation between the dentist and the doctor who treats the underlying disease.

Statins use and peripheral blood progenitor cells mobilization in patients with multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17007-e17007
Author(s):  
Ioannis Voutsadakis ◽  
Athina Stravodimou
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Blood ◽  
Statistical Significance ◽  
Median Number ◽  
Control Group ◽  
High Dose ◽  
Target Number ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
Cd34 Cells

e17007 Background: Statin drugs have beneficial effects in patients after myocardial infarction and at least part of the benefit is believed to result from mobilization of marrow endothelial progenitors to repopulate damage myocardial tissues. This study examines if statins may have the same effect in mobilizing marrow progenitors to be harvested and subsequently used in high dose chemotherapy with progenitor cell rescue in patients with multiple myeloma. Methods: From 2006 to 2009, 22 consecutive patients with multiple myeloma were mobilized with the use of G-CSF and were retrospectively analyzed. Patients with other malignancies or mobilized with the use of chemotherapy or with plerixafor were excluded from this analysis. Results: The median age of the patients was 60 years-old. Fifteen patients had received one line of chemotherapy, six patients two lines and one patient three lines of chemotherapy. Thirteen patients were taking statins at the time of the harvest while nine patients were not. In the group of patients taking statins in only two of 13 (15%) the target number of 4x106 CD34+ cells /kg could not be obtained with a single apheresis session while in the group not taking statins four of nine patients (44.5%) required more than one session to obtain this target (including one patient in whom the target number could not be obtained even with the additional sessions). Nevertheless due to the low number of patients in the study this difference did not attain statistical significance (x2=0.13). The median number of cells harvested was 8x106 CD34+ cells /kg in the group taking statins and 6.3x106 CD34+ cells /kg in the control group. Conclusions: This retrospective analysis of 22 patients discloses a numerically important difference in the success of peripheral blood progenitors harvest in patients taking statins which did not attain statistical significance. Larger studies would be required to clarify the issue. If their effectiveness is confirmed statins could be a safe and cheaper addition to chemotherapy and plerixafor for peripheral hematopoietic stem cell mobilization.

Erythropoietin Treatment in Advanced Multiple Myeloma Is Associated with Improved Immunological Functions: Could It Be Beneficial in Early Disease?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3499-3499
Author(s):  
Sara Prutchi-Sagiv ◽  
Nataliya Golishevski ◽  
Howard S. Oster ◽  
Odelia Katz ◽  
Naparstek Elizabeth ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Early Stage ◽  
Healthy Controls ◽  
Immune Functions ◽  
Immunological Parameters ◽  
Number Of Patients ◽  
Erythropoietin Treatment ◽  
Cd8 Cell ◽  
Stage 1 ◽  
Immunological Abnormalities

Abstract Erythropoietin (Epo), the main growth regulator of erythropoiesis, is being used to treat anemias associated with renal disease and malignancies. We have previously observed prolonged survival of patients with advanced multiple myeloma (MM) who were treated with recombinant human Epo (rHuEpo) (Mittelman et al, Eur J Haematol2004:72:155). Further studies on murine MM models confirmed this observation and suggested that Epo has an anti-MM immunomodulatory effect (Mittelman et al. Proc Natl Acad Sci USA2001:98:5181; Katz et al. Acta Haematol2005:114:177). We have reported (ASH 2004) preliminary results showing that the rHuEpo-treated MM patients acquired improved immunological functions. We have since then extended the numbers of patients and the range of immunological functions tested. Here, we show that rHuEpo, prescribed for anemia in patients with advanced MM (Durie and Salmon Stage 2–3), is associated with effects on a variety of immunological parameters and functions, as presented in the table. Compared with non rHuEpo-treated MM patients, who demonstrated immunological abnormalities, rHuEpo-treated MM patients resumed normalization of the CD4:CD8 cell ratio, enhanced T-cell (both CD8 and CD4) PHA-mediated activation, improved mononuclear proliferation potential, higher expression of the co-stimulatory molecule CD28, lower values of the inhibitory CTLA-4 molecule and decreased levels of serum IL-6. The immunological parameters in the rHuEpo-treated MM patients were close to the normal healthy controls. Results are presented in the table below (mean +/− SE). We also found similar immunological abnormalities in patients at an early stage (Durie and Salmon stage 1, smoldering) MM (n=8). Our findings a) confirm and extend reports by others regarding immunological abnormalities in patients with advanced MM; b) show that patients with advanced MM treated with rHuEpo for their anemia benefit from improved immunological functions; c) show that patients with early-stage MM already manifest similar immunological abnormalities. Our data thus indicate that patients with early-stage MM might benefit from rHuEpo with improved immune functions, even prior to the development of anemia in later stages of the disease. Taken together, our study suggests rHuEpo as a potential immunomodulatory agent in the treatment of MM. Parameter Normal Healthy Controls MM Patients rHuEpo-treated Advanced MM Patients Early MM Advanced MM a. p<0.05 advanced MM compared to healthy controls. b. p<0.05 early MM compared to health controls. c. p<0.05 rHuEpo treated advanced MM compared to non-treated advanced MM patients Number of Patients N=14 N=8 N=21 N=13 CD4:CD8 2.4±0.3 1.2±0.2b 1.2±0.1a 1.9±0.3c PHA act- CD8+CD69+ (%) 60±4.4 45±4.4b 46.3±3a 63.3±3.8c PHA act-CD4+CD69+ (%) 57.1±3.8 42±4.6b 43.3±3a 59.9±3.6c Proliferation (%) 232.5±10.3 161±7.1b 146.5±15.1a 218.1±22.5c CD8+CD28+ (%) 73.2±5.2 53.7±8.2 38.8±2a 55.6±2.9c CD8+CTLA-4+ (%) 2.4±0.6 12.5±3.6 10.1±1.5a 4.6±0.9c sIL-6 (pg/ml) 2.6±0.4 5.4±1 10±2.1a 5.7±0.9c

A Staged Approach to the Use of Bortezomib/Thalidomide/Dexamethasone (VTD) in Multiple Myeloma Patients with Suboptimal Initial Cytoreduction Led to a High Complete Remission Rate

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5202-5202
Author(s):  
Chor Sang James Chim ◽  
Raymond Liang
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Remission Rate ◽  
Staging System ◽  
Hematopoietic Stem ◽  
Stage Disease ◽  
Tumor Load ◽  
International Staging System ◽  
Staged Approach

Abstract Autologous hematopoietic stem cell transplantation (AHSCT) and bortezomib are the two most important advances in the treatment of multiple myeloma (MM) in the last decade. Autologous HSC harvest is preferably performed at complete remission (CR) or after maximal reduction of myeloma tumor load. Owing to the high cost of bortezomib, we devised a total therapy incorporating VAD (vincristine, adriamycin, dexamethasone), followed by VTD in those with inadequate cytoreduction (i.e. &lt;75% reduction in paraprotein) to maximize eradication of myeloma cells in the marrow prior to HSC harvest. Those achieving &gt;75% paraprotein reduction proceeded to AHSCT directly. Those with measurable disease after the first AHSCT proceeded to second AHSCT. Response was based on the EBMT criteria (Blade et al, 1998). There were 16 patients with a median age of 50 years (33–64). Majority had advanced stage disease by International staging system. After VAD, 6 patients had &gt;75% response (&gt;90% response, n=3; 75%–90% response, n=3) and hence proceeded to first AHSCT directly. The other 10 patients had VTD salvage therapy, which upgraded response in 9 cases. After VAD and VTD treatments, there were 2, 6,7 and 1 patients achieving CR, &gt;90% response, 75%–90% response and no response respectively. Thirteen patients proceeded to the first AHSCT, which rendered upgrading of response in 9 patients (69%) with CR/near CR in 7 cases (54%) and &gt;90% response in 4 cases (31%). The latter 4 patients proceeded to second AHSCT, resulting in CR/near CR in 9 cases (70%) and &gt;90% in 2 cases (15%). Of the 11 patients with &gt;90% response after first and/or second AHSCT, 5 patients had maintained response with continual CR in 4 cases, whereas 6 patients relapsed (with asymptomatic disease in 4 cases and fatality in 2 cases). Therefore, this strategy of employing bortezomib only in those with insufficient cytoreduction achieved a high CR/near CR rate comparable to that with upfront bortezomib use. However, the frequent relapse implied that the quality of CR is equally important. Moreover, the aggressive fatal relapse in CR patients demonstrated a biologically aggressive subgroup in which CR might be inadequate.

scholarly journals Evaluation of a routine screening program with tuberculin skin testing on rates of detection of latent tuberculosis infection and prevention of active tuberculosis in patients with multiple myeloma at a Canadian cancer centre

2020 ◽  
Vol 27 (3) ◽  
Author(s):  
M. Gitman ◽  
J. Vu ◽  
T. Nguyen ◽  
C. Chen ◽  
C. Rotstein
Keyword(s):  
Multiple Myeloma ◽  
Screening Program ◽  
Skin Testing ◽  
Routine Screening ◽  
Screening Tests ◽  
Tuberculous Infection ◽  
Tuberculin Skin Testing ◽  
Hematopoietic Stem ◽  
Cancer Centre ◽  
Number Of Patients

Background Chemotherapy-induced T cell dysfunction, resulting from treatment of multiple myeloma (mm), enhances the risk for reactivation of latent tuberculous infection (ltbi). However, routine screening for ltbi has its limitations. The objective of the present study was to assess the number of patients treated for ltbi both before and after the introduction of a consistent tuberculin skin test (tst) screening program for patients with mm at our cancer centre. Methods This retrospective observational study analyzed adult patients with mm treated with autologous hematopoietic stem-cell transplantation from 1 January 2013 to 31 December 2014, for whom tst was consistently performed at our cancer facility. Baseline demographic characteristics of patients who received tst testing and ltbi therapy were compared with those of a pre intervention cohort of patients (1 January 2008 to 31 December 2009) who were not tested. Results During the post-intervention period, 170 patients with mm had a tst. In 14 patients (8.2%) results were positive, and 11 of the 14 received ltbi therapy. Of another 12 patients with radiographic imaging changes consist with prior granulomatous disease and negative tst results, 2 were treated. No cases of tuberculosis (tb) reactivation were noted in individuals who completed ltbi therapy. One case of active tb was diagnosed in a patient with a negative tst. In contrast, in the pre-intervention matched cohort of 170 patients, no tsts were performed, and no cases of active tb were documented. Conclusions Patients with mm could benefit from a consistent tst testing policy coupled with subsequent ltbi therapy. However, universal testing might not be required. A targeted program combining evaluation of host risk factors, imaging findings, and screening tests might optimize ltbi diagnosis and management, and thus be effective in preventing the development of active tb in at-risk patients with mm.

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