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

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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1577. 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 Center

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1405 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S492-S493

Author(s):

Melissa Gitman ◽

James Vu ◽

Tram Nguyen ◽

Coleman Rotstein ◽

Christine Chen

Keyword(s):

Multiple Myeloma ◽

Latent Tuberculosis Infection ◽

Screening Program ◽

Skin Testing ◽

Latent Tuberculosis ◽

Active Tuberculosis ◽

Tuberculosis Infection ◽

Cancer Center ◽

Tuberculin Skin Testing ◽

Routine Screening Program

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

Blood ◽

10.1182/blood.v118.21.4124.4124 ◽

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.

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Natural History of Post-Allogeneic HSCT EBV-Reactivation: A Single Center Retrospective Survey.

Blood ◽

10.1182/blood.v106.11.3232.3232 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3232-3232

Author(s):

Helene M. Schoemans ◽

Koen Theunissen ◽

Marc Boogaerts ◽

Johan Maertens

Keyword(s):

Opportunistic Infections ◽

Screening Tests ◽

Rt Pcr ◽

Post Transplantation ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

Ebv Reactivation ◽

Number Of Patients ◽

Significant Difference

Abstract Epstein Barr Virus (EBV) reactivation occurs in about 50% of the allogeneic hematopoietic stem cell transplantation (HSCT) population in the first year post-transplantation. About 1-7% of these patients run the risk of developing a post-transplant lymphoproliferative disorder (PTLD). Several authors have thus advocated systematic screening by EBV real time PCR (RT-PCR) to initiate pre-emptive treatment of reactivations using Rituximab (van Esser 2002). However, the positive predictive value of EBV RT-PCR is only of 40% (van Esser 2001), implying that this algorithm overtreats a number of patients. Methods: We have retrospectively analyzed 60 consecutive allogeneic HSCT patients transplanted in our center between 1/1/2004 and 31/3/2005. Four patients were excluded because of absence of EBV follow-up (n=2) or autologous reconstitution (n=2). EBV reactivation (EBV (+)) was defined by at least two consecutive episodes of EBV RT-PCR above 1000 copies/ml of whole blood. Any other result was considered as negative (EBV (−)). Results: 1175 EBV RT-PCR samples were collected over a median follow up of 215 days (range: 21–511). The population observed was essentially adults (median age 42 years, range: 1–65) with leukemia (29 leukemia, 11 lymphomas, 16 other diseases), mixed graft types (26 matched sibling donors, 26 matched unrelated donors, 4 haploidentical donors; 77% peripheral blood stem cells; 20% CD34+ selection) and mixed conditioning (52% non-myeloablative conditioning containing ATG, and 48% full conditioning). The EBV(+) and EBV(−) cohorts were similar for all characteristics analyzed. We observed a median of 18 EBV RT-PCR per patient (range: 4–105), with a median interval between two tests of 7 days (range: 3–45). There were 30 true reactivations, 2 intermittent reactivations (non consecutive EBV titer rises above threshold), 8 isolated reactivations and 16 patients with no reactivation episode. EBV RT-PCR was first performed at a median of 6 days post HSCT (range: 0–245), and reactivation was noted at a median of 44 days post HSCT (range: 6–375). There were no significant difference in PCR follow up (first day of screening, median test interval and length of biological follow up) except for the total number of screening tests per patient, which was higher in the EBV(+) group (p= 0.01). There was only one case of biopsy-proven PTLD in the EBV(+) cohort. No patient was administered Rituximab post- HSCT. Survival curves of the two cohorts were similar regardless of EBV reactivation (log-rank, p= 0.201). Discussion: The incidence of EBV reactivation (n= 30; 54%) and of PTLD (n=1;1.7%) were standard compared to previous studies, resulting in a standard specificity of 47% for EBV screening. However, within our limited group of patients, we could not show any significant differences in mortality between the EBV(+) and EBV (−) cohorts. Therefore, absence of preventive treatment for EBV reactivation did not result in an increase in mortality in our EBV reactivating cohort. This suggests that systematic prophylactic use of Rituximab may not affect overall mortality, whilst potentially increasing the risk of other opportunistic infections. Conclusion: Further prospective studies are needed to better define the patients at risk for developing EBV-related PTLD, within the EBV reactivating allogeneic transplant patients group, before prophylactic treatment of reactivation becomes a routine procedure.

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

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e17007 ◽

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.

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

Blood ◽

10.1182/blood-2021-154489 ◽

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.

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