scholarly journals 1741. Invasive Fungal Infections in Patients with Multiple Myeloma in the Era of Novel Therapies

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S637-S638
Author(s):  
Emily Baneman ◽  
Ajai Chari ◽  
Meenakshi Rana ◽  
Dallas Dunn ◽  
Timothy Sullivan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progressive Disease ◽  
Fungal Infections ◽  
Checkpoint Inhibitors ◽  
Univariate Analysis ◽  
Retrospective Chart Review ◽  
Disease Status ◽  
Antifungal Prophylaxis ◽  
Cell Transplant ◽  
The Impact

Abstract Background Rapid advances in multiple myeloma (MM) therapy have led to improved survival, yet the impact of novel agents on the risk of invasive fungal infection (IFI) is largely unknown. We aim to describe the epidemiology of IFIs in MM patients in the current era of chemotherapy. Methods We performed a retrospective chart review of MM patients at Mount Sinai Hospital in New York, NY who entered care between December 2009 and October 2016 and had proven or probable IFI between January 2011 and October 2017. Probable and proven IFIs were defined by revised EORTC/MSG criteria. Descriptive statistics are reported as median (range). We evaluated factors associated with mortality by univariate analysis using Fisher’s exact and Mann–Whitney U tests. Results 2,960 MM patients entered care during the study period. We identified 30 episodes of IFI among 29 patients. Median age was 59 (42–80) years and 21 (70%) were men. IFI occurred at a median of 3.7 (0.3–18) years from MM diagnosis. At the time of IFI diagnosis, patients had received a median of 4 (1–12) lines of chemotherapy, 18 (60%) had undergone autologous stem cell transplant (ASCT), and 21 (70%) had progressive disease status. Agents received immediately prior to IFI were immunomodulators (n = 14), proteasome inhibitors (n = 14), conventional chemotherapy (n = 11), monoclonal antibodies (n = 6), checkpoint inhibitors (n = 3) and other (n = 3). Twenty-two (73%) patients received corticosteroids in the prior 30 days. Neutropenia and lymphopenia were present in 12 (40%) and 13 (43%) patients, respectively. There were 9 proven and 21 probable IFIs: invasive aspergillosis (n = 19), candidemia (n = 5), cryptococcosis (n = 3), talaromycosis (n = 1), mucormycosis (n = 1) and other (n = 2). Bacterial and viral respiratory co-infections occurred in 7 and 4 patients, respectively. Eight (27%) patients required ICU admission and 9 (30%) died within 30 days of IFI diagnosis. In univariate analysis, number of lines of chemotherapy (P = 0.05), progressive disease status (P = 0.03), and prior ASCT (P = 0.004) were associated with 30-day mortality. Conclusion IFIs are uncommon in MM patients receiving newer agents but are associated with significant morbidity and mortality. Further study is needed to identify high-risk subgroups that may benefit from antifungal prophylaxis or increased surveillance. Disclosures All authors: No reported disclosures.

scholarly journals The Use of Voriconazole as Primary Prophylaxis for Invasive Fungal Infections in Patients Undergoing Allogeneic Stem Cell Transplantation: A Single Center’s Experience

2021 ◽  
Vol 7 (11) ◽  
pp. 925
Author(s):  
Ali Atoui ◽  
Nadine Omeirat ◽  
Omar Fakhreddine ◽  
Raquelle El El Alam ◽  
Zeina Kanafani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Invasive Aspergillosis ◽  
Fungal Infections ◽  
Univariate Analysis ◽  
Disease Status ◽  
Primary Prophylaxis ◽  
Invasive Fungal Infections ◽  
High Morbidity ◽  
Cell Transplant ◽  
Free Survival

Background: Invasive fungal infections (IFI) following allogeneic stem cell transplant (allo-HCT) are associated with high morbidity and mortality. Primary prophylaxis using voriconazole has been shown to decrease the incidence of IFI. Methods: We conducted a retrospective analysis at the Bone Marrow Transplant (BMT) unit of the American University of Beirut including 195 patients who underwent allo-HCT for hematological malignancies and received voriconazole as primary prophylaxis for IFI. The primary endpoints were based on the incidence of IFI at day 100 and day 180, and the secondary endpoint based on fungal-free survival. Results: For the study, 195 patients who underwent allo-HCT between January 2015 and March 2021 were included. The median age at transplant was 43 years. Of the patients, 63% were male, and the majority of patients were diagnosed with acute myeloid leukemia (AML) (60%). Voriconazole was given for a median of 90 days and was interrupted in 20 patients. The majority of IFI cases were probable invasive aspergillosis (8%). The incidence of IFI including proven, probable and possible IFI was 34%. The incidence of proven and probable IFI was 5% were 8%, respectively. The incidence of proven-probable (PP-IFI) was 5.1% at day 100 and 6.6% at day 180. The majority of PP-IFI cases were invasive aspergillosis (8%). A univariate analysis of patients, transplant characteristics and IFI showed a significant correlation between the type of donor, disease status before transplant, graft-versus-host disease prophylaxis used and incidence of IFI. Only disease status post-transplant showed a significant correlation with fungal-free survival in the multivariate analysis. Conclusion: Primary prophylaxis with voriconazole in allo-HCT is associated with a low incidence of IFI. More studies are required to compare various antifungal agents in this setting.

scholarly journals 962. Linkage to Care Outcomes among Known HIV-Positive Patients at a High Prevalence Urban Hospital Emergency Department

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S511-S511
Author(s):  
Alexander W Sudyn ◽  
Jeffrey M Paer ◽  
Swetha Kodali ◽  
Samuel Maldonado ◽  
Amesika Nyaku ◽  
...  
Keyword(s):  
Hiv Risk ◽  
Hiv Transmission ◽  
Univariate Analysis ◽  
Linkage To Care ◽  
Retrospective Chart Review ◽  
Retention In Care ◽  
Patient Navigator ◽  
Urban Hospital ◽  
Opt Out ◽  
The Impact

Abstract Background Retention in care of persons with HIV (PWH) is essential for achieving viral suppression and decreasing community transmission. CDC estimates that the 23% of known PWH not retained in care account for 43% of all new transmissions. This study seeks to describe the impact of an opt-out ED screening with navigator-assisted linkage to care (LTC) protocol for out of care PWH. Methods An IRB-approved retrospective chart review was conducted among PWH (prior positive) inadvertently retested in the ED between 2015 and 2018. Univariate and multivariate logistic regression was used to identify factors associated with LTC with patient navigator (PN) support. Factors with p ≤ 0.1 were included in the multivariate analysis as were age and sex at birth. Patients who died were excluded from statistical analyses. Results Among 464 patients who tested positive, 338 (73%) were known positive with 120 (35%) of those out of care at the time of screening. Mean age for this group was 47 (SD 11.9); 57% male, 81% non-Hispanic black, 10% Hispanic, and 6% non-Hispanic white. Fifty-five (46%) patients were successfully LTC, 54 (45%) referred to the state for linkage, and 11 (9%) died. A total of 109 patients were included in the analysis. Univariate analysis was performed for age (F(1, 107) = 0.98, p = 0.324) and female sex at birth (OR = 1.42 [95% CI 0.66, 3.05], p = 0.373) as well as Hispanic race (OR = 3.33 [95% CI 0.84, 13.04], p = 0.085), heterosexual HIV risk (OR = 2.76 [95% CI 1.27, 5.99], p = 0.011), IDU (OR = 0.49 [95% CI 0.21, 1.11], p = 0.088), and other SUD (OR = 0.42 [95% CI 0.19, 0.94], p = 0.035). Only heterosexual HIV risk (OR = 3.01 [95% CI 1.23, 7.32], p = 0.015) maintained significance in the final multivariate model. Conclusion Opt-out ED screening revealed >30% of known positive PWH were out of care at the time of testing; of whom nearly 50% were LTC with PN support. It is possible that persons reporting heterosexual HIV risk may feel less stigmatized and therefore are more likely to LTC. Similarly, the association with SUD, albeit non-significant, may reflect underrepresentation of individuals with SUD in remission among patient navigators. Future opt-out ED screening protocols should build upon diverse care teams to further engage patients with SUD and those at risk for non-heterosexual HIV transmission. Disclosures All Authors: No reported disclosures

scholarly journals Impact of Amotosalen/UVA Pathogen Inactivated Platelet Components on Outcomes after Allogeneic Hematopoetic Stem Cell Transplantation: A Single Center Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1167-1167
Author(s):  
Andreas S. Buser ◽  
Laura Infanti ◽  
Andreas Holbro ◽  
Joerg Halter ◽  
Sabine Gerull ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Risk Scores ◽  
Employment Equity ◽  
Stem Cell Source ◽  
Equity Ownership ◽  
The Impact

Background: Platelet component (PC) transfusion is required for allogeneic hematopoietic stem cell transplantation (HCT) recipients. Contamination with infectious pathogens (bacteria, viruses, or protozoa) and T-cells is a risk factor for transfusion-transmitted infection (TTI) and transfusion associated graft-versus-host disease (TA-GVHD). Pathogen inactivation (PI) treatment of PC with amotosalen-UVA (PI-PC, INTERCEPT Blood System, Cerus Corp) in platelet additive solution (PAS) without bacterial screening, gamma irradiation, CMV serology, and with 7-day storage has been the standard of care in Switzerland since 2011 to manage risk of TTI and TA-GVHD. PI-PC have replaced conventional PC (C-PC) prepared in PAS with gamma irradiation and 5 day storage. We previously reported platelet usage in two consecutive five year periods at the University Hospital of Basel. Mean PI-PC dose was higher (3.0 vs. 2.8 x 1011, p=0.001) and mean storage duration longer (4.2 vs. 3.4 days: p=0.001) than with C-PC. PC expiration wastage was reduced with 7-day PI-PC storage vs. 5-day storage (1.5% vs. 8.7%). For HCT recipients, days of PC support; PC use per patient; and RBC use per patient were similar, despite 24.3% lower corrected count increments (CCI) with PI-PC. Now, we report the impact of these observations on treatment related mortality (TRM) and overall survival (OS) 100 days after HCT. Patients and Methods: A two-period retrospective cohort study was conducted to evaluate PI-PC impact on outcomes of consecutive first allogeneic HCT recipients from January 2006 to December 2010 (Period 1, P1), when gamma-irradiated apheresis C-PC were used, and Period 2 (P2) from January 2011 to December 2017, when apheresis and whole blood-derived PI-PC were used. The review utilized 100-day OS and 100-day TRM to determine the impact of PI-PC on HCT outcomes. Descriptive statistics were used for continuous variables and log-rank analysis for survival outcomes. Univariate analysis was performed using Pearson χ2 statistics. Multivariate Cox regression modelling analyses included: PC period (P1, P2), donor match (HLA identical/twin, matched related, matched unrelated), disease state (early, intermediate, late), and conditioning regimen (reduced intensity, myeloablative) with TRM as the outcome. This was an IRB approved single-center analysis. Results: In P1 and P2, 256 and 557 consecutive first-time allogeneic HCT recipients were included, respectively. By univariate analysis, the distribution of European Group for Bone Marrow Transplantation (EBMT) risk scores (grouped 0-2, 3-4, 5-7) and mean patient age were higher during P2 (p = 0.001 and p <0.001, respectively). Primary disease status (p = 0.039); stem cell source (p <0.001); GVHD prophylaxis with ATG (p <0.001); total body irradiation (p <0.001); and conditioning regimen (p <0.001) were different between P1 and P2. Donor match (p=0.084) and disease status (p = 0.628) were similar in P1 and P2. TRM at day 100 post HCT was significantly less (31/557, 5.5%) for PI-PC recipients in P2 vs. C-PC recipients in P1 (37/256, 14.5%, p<0.001). Overall proportion of survivors at day 100 post HCT was significantly greater for PI-PC recipients (507/557, 91.0 %) compared to C-PC recipients (209/256, 81.6%, p <0.001). By multivariate Cox regression analysis, P2 with PI-PC component support was associated with improved TRM (p = 0.001; adjusted hazard ratio 0.433; 95% confidence interval: 0.262, 0.716). Donor match (p = 0.019), disease state (p = 0.022), and myeloablative conditioning (p = 0.034) were associated with significantly poorer TRM (Table). Stem cell source was not significant (p=0.157) in the model. Hemorrhage was reported as cause of death in 1/50 (2.0%) patients during P2 with PI-PC and 4/47 (8.5%) patients during P1 with C-PCs. Conclusions: Universal implementation of PI-PC in routine with extended storage to 7 days in P2 was associated with reduced TRM and better overall survival 100 days post HCT, despite transplantation of older patients with higher EBMT risk scores. Multivariate analysis revealed an adjusted hazard ratio of 0.433 (95% C.I. 0.262, 0.716) for TRM by 100 days, suggesting better outcomes in P2. This retrospective analysis at a single site indicated that PI-PC treated with amotosalen /UVA stored up to 7 days did not have a negative impact on TRM and OS in HCT recipients, and was an integral part of improving clinical outcomes at our institution. . Table. Disclosures Heim: Novartis: Research Funding. Irsch:Cerus Corporation: Employment, Equity Ownership. Lin:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership. Corash:Cerus Corporation: Employment, Equity Ownership.

Treatment response among patients with multiple myeloma initiating daratumumab across different lines of therapy: A real-world chart review study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18737-e18737
Author(s):  
Shebli Atrash ◽  
Philippe Thompson-Leduc ◽  
Ming-Hui Tai ◽  
Shuchita Kaila ◽  
Kathleen Gray ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Treatment Response ◽  
Real World ◽  
Chart Review ◽  
Response Rate ◽  
Retrospective Chart Review ◽  
Case Report Form ◽  
Combination Regimen ◽  
Cell Transplant ◽  
Effective Treatment Option

e18737 Background: Daratumumab (DARA), a CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma (MM) among previously-treated patients since 2015, and among newly-diagnosed patients since 2018. This study aimed to describe real-world treatment response among patients initiating DARA across different lines of therapy since 2018. Methods: A retrospective chart review of adult patients with MM initiating DARA (monotherapy or as part of a combination regimen) between 1/2018 and 5/2020 was conducted at two clinical sites in the US (Levine Cancer Institute & Weill Cornell Medical College). De-identified patient-level data were abstracted in an electronic case report form. Treatment patterns, overall response rate (ORR) and proportion of patients with very good partial response (VGPR) or better were reported using descriptive statistics and stratified by line of therapy (first line [1L], second line [2L] or third line or later [3L+]). Results: A total of 202 patient charts were extracted. Patients were, on average, 65.3 years old at MM diagnosis and 68.1 years old at DARA initiation; 109 (54.0%) were male; 104 (51.5%) were White and 65 (32.2%) were Black or African American; 64 (31.7%) received a stem cell transplant (SCT) prior to the line of DARA initiation. Twenty-one (10.4%), 53 (26.2%) and 128 (63.4%) patients initiated DARA in 1L, 2L and 3L+, respectively. Median follow-up time was 6.2 months for 1L patients and 13.8 months for 2L+ patients. The most common 1L regimen was DARA with bortezomib, lenalidomide ± dexamethasone (DVRd; n=10, 47.6%) followed by DARA with lenalidomide ± dexamethasone (DRd; n=8, 38.1%). The most common 2L regimen was DRd (n=15, 28.3%) followed by DARA with pomalidomide ± dexamethasone (DPd, n=13, 24.5%) and DARA with bortezomib ± dexamethasone (DVd, n=13, 24.5%). The most common regimen in 3L+ was DPd (n=62, 48.4%). Among patients initiating DARA in 1L, 2L or 3L+ the ORR was 100.0%, 81.6% and 76.0%, and the proportion of patients achieving VGPR or better was 73.3%, 65.8% and 51.0%, respectively (Table 1). Median time to treatment response ranged between 2.6 and 2.8 months post-initiation. Conclusions: In this study, patients initiated on DARA had high ORR and rates of VGPR or better, including an ORR of 100% among 1L DARA users. These findings suggest that DARA-based regimens are an effective treatment option across all lines of therapy, with highest response rate in 1L. [Table: see text]

scholarly journals 240. The Clinical Utility of Molecular Testing in the Diagnosis and Management of Infectious Diseases: Plasma-based Next-Generation Sequencing (PNGS)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S136-S136
Author(s):  
Jim H Nomura ◽  
Townson Tsai
Keyword(s):  
Fungal Infections ◽  
Retrospective Chart Review ◽  
Blood Cultures ◽  
Common Reason ◽  
Clinical Indication ◽  
Molecular Diagnostic ◽  
Cns Infection ◽  
Molecular Testing ◽  
Disseminated Disease ◽  
The Impact

Abstract Background Molecular diagnostic tests can provide microbiologic results rapidly and with greater sensitivity than traditional methods. However, these tests come with considerable costs, so thoughtful diagnostic stewardship is essential to ensure that resources and outcomes are optimized. We sought to evaluate the impact of PNGS testing on patient management. Methods From February 2017 to January 2019, physicians in our group ordered 164 PNGS tests (Karius, Redwood City CA) on 125 patients. A retrospective chart review was performed to determine the clinical indication and utility of the test. Results The assay failure rate was 4.9% (8/164). Positive (pos) results were noted in 34% (53/156), of which 23 (43.4%) represented false pos results; 28 were true pos (52.8%) but 2 were unnecessary (also had pos blood cultures). The most common reason for testing was to assess for Mycobacterium chimera (Mc) infection, representing 94 of 156 (60.3%) tests. Of the 21 patients with known Mc, only 10/21 had pos initial tests (47.6%); if patients with Mc localized to the sternum were excluded (8 patients), 76.9% with deep organ involvement had pos initial tests. Five patients with deep Mc infection had persistently pos results while on therapy; 4 of these had not had surgery; 1 was 6 months s/p valve replacement for Mc. The next most common indication was to r/o endocarditis in 18/156 (11.5%) and had an impact in 8/18 (44.4%), including 4 patients whose PNGS result identified a likely pathogen in culture negative endocarditis (CNE). Of the 62 tests done for non-Mc patients, 33.9% (21/62) were useful for management decisions. Among patients who eventually had a diagnosis made but had negative PNGS results included patients with Whipple’s (1), CNS infection (2), and fungal infections (5). Conclusion Overall, only 17.9% (28/156) of tests yielded true pos results. The most common reason was to evaluate for Mc infection. PNGS did not detect Mc in patients with proven local disease and was pos in >75% with deep/disseminated disease. However, a negative result did not exclude significant Mc infection. Repeat testing can be considered if clinical suspicion is high but should not be done before standard blood cultures are negative. While more than 60% of the non-Mc tests were not clinically useful, there was modest added utility where infection is high on the differential especially patients with CNE. Disclosures All authors: No reported disclosures.

Second Autologous or Allogeneic Transplantation after the Failure of First Autograft in Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3329-3329
Author(s):  
Muzaffar H. Qazilbash ◽  
Rima Saliba ◽  
Marcos de Lima ◽  
Daniel Couriel ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
Albumin Level ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Common Causes

Abstract Background: Most patients undergoing high-dose therapy and autologous transplant for multiple myeloma eventually relapse. The optimal salvage treatment for these patients is not very well defined. Both autologous and allogeneic hematopoietic stem cell transplantations have been used for salvage. We analyzed the outcomes of second autologous or allogeneic transplants, performed as salvage in patients relapsing after an autograft. Methods: Fourteen patients received a second autograft for salvage, while thirty-four patients underwent allogeneic transplantation (related 24, unrelated 10). The median age at transplant was 52 years in the autologous group, and 51 years in the allogeneic group. The median interval between the first and the second transplant was 25 months in the autologous group and 17 months in the allogeneic group. The disease characteristics were similar in both autologous and allogeneic groups. Results: With a median follow-up of 10 months among survivors in each group, both autologous and allogeneic transplant groups had a response rate (complete + partial) of 64%. One hundred day nonrelapse mortality was 7% in the autologous group and 12% in the allogeneic group. Median disease-free survival (DFS) was 11 months in the autologous and 6 months in the allogeneic group. Median overall survival (OS) was 29 moths in the autologous and 14 months in the allogeneic group. 1-year DFS was 40% in the autologous group and 22% in the allogeneic group (p = 0.2). 1-year overall survival was 70% in the autologous and 53% in the allogeneic group (p = 0.3). The most common causes of non-relapse mortality were graft vs. host disease (62%) in the allogeneic group, and infections (100%) in the autologous group. On univariate analysis for DFS in allogeneic group, an interval of >1 year between the first and the salvage transplant was the only factor associated with a significantly better outcome (p = 0.01). Disease status at transplant, type of donor, tumor mass, β2 microglobulin level, and serum albumin level did not show any impact on the outcome. Conclusions: Both autografting and allografting are feasible as salvage for myeloma patients relapsing after the first autograft. A slightly better outcome with salvage autografting may be due to decreased toxicity.

Second Autologous Stem Cell Transplant (ASCT) as Salvage Therapy for Relapsed Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1170-1170
Author(s):  
Rebecca L. Olin ◽  
David L. Porter ◽  
Selina M. Luger ◽  
Stephen J. Schuster ◽  
Donald Tsai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Treatment Options ◽  
Univariate Analysis ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Response To Therapy ◽  
Cell Transplant ◽  
Significant Difference

Abstract Introduction: Autologous stem cell transplant (ASCT) as part of initial therapy has been shown to prolong survival of patients with multiple myeloma, with some achieving durable complete remission. However, the majority of patients ultimately relapse after ASCT and require salvage treatment. Options for the treatment of such patients have increased significantly over recent years, including not only novel chemotherapeutic and biological agents but also additional ASCTs. We performed a retrospective analysis of our experience with salvage ASCT for multiple myeloma to determine which clinical variables influence outcome. Methods: Between October 1992 and February 2005, we performed 342 ASCTs for multiple myeloma. Twenty-six of these were salvage transplants for relapsed disease after prior ASCT, and all were included in the analysis. Patients who received two planned (tandem) ASCTs were not included. Results: The median age at diagnosis was 47 (range 25–66), and median ISS and DS stages at diagnosis were 1 and 2, respectively. The initial ASCT was melphalan-based in 21/26; six (23%) achieved a complete response (CR) to the initial transplant, and fifteen (58%) achieved a partial response (PR). The median event-free survival (EFS) after the initial transplant was 19.5 months (range 2–60). The median time between initial and salvage ASCT was 2.6 years (range 0.3–7.6). Twenty-two patients (85%) received non-transplant therapy between ASCTs, and the median number of lines of therapy prior to salvage ASCT was 3. At the time of salvage ASCT, the median age was 52.5 (range 28–69). Fourteen patients received melphalan alone, eight received melphalan/TBI, and four received other regimens. Eleven patients (42%) achieved a response to therapy (1 CR, 10 PR). One patient (4%) died of transplant-related toxicity. The median follow-up after salvage ASCT is 12 months (range 0.2–58). Median EFS is 9 months, and median overall survival (OS) is 36 months. The 2-year EFS is 14%, and 2-year OS is 52%. On univariate analysis, both response to and EFS after initial transplant significantly predict improved EFS after salvage transplant (p=0.0008 and p=0.0065 respectively). Both also predict improved OS (p=0.03 and 0.0005 respectively). A greater than 12 month interval between first and second transplant also correlated with OS (p=0.04). There was no significant difference in EFS or OS by preparative regimen. Interestingly, type of response to the salvage transplant (CR/PR or less than PR) did not predict improved EFS or OS. Conclusion: This study suggests that salvage ASCT after relapse from initial ASCT is a feasible therapy for patients with heavily treated multiple myeloma, particularly those with a prolonged response to the first transplant.

Early Lymphocyte Recovery Predicts Superior Survival after Autologous Peripheral Blood Stem Cell Transplantation (ASCT) in Patients with Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5487-5487
Author(s):  
Devendra K. Hiwase ◽  
Anthony P. Schwarer ◽  
Geraldine M. Bollard ◽  
Smita D. Hiwase ◽  
Michael Bailey
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Prognostic Marker ◽  
Lymphocyte Count ◽  
Progressive Disease ◽  
Prognostic Indicator ◽  
Cell Transplant ◽  
The Difference

Abstract Aim: ASCT has improved survival in patients with multiple myeloma although most patients develop progressive disease. Absolute lymphocyte count recovery at day 15 (ALC-15) following ASCT has been reported as an independent prognostic indicator of overall survival (OS) and progression free survival (PFS) for patients with multiple myeloma. It is not only a good prognostic marker but may also have therapeutic significance. We evaluated absolute lymphocyte recovery on day 15 (ALC-15), day 30 (ALC-30), day 60 (ALC-60) as a prognostic marker following ASCT in patients with multiple myeloma. Method: Between 1992 and 2004, 119 consecutive patients underwent ASCT. ALC-15, ALC-30, ALC-60 were evaluated for impact on OS and PFS following ASCT. Information on known prognostic factors for multiple myeloma including age, BM plasma cells (PC), paraprotein (PP), international staging system (ISS staging) and disease response following stem cell transplant were also evaluated. Result: There were 119 (M/F, 79/43) patients and median age was 57 (30–70) years. Most patients (N=100) received melphalan 200 mg/m2 as conditioning chemotherapy. The median CD34 dose infused was 3.95 x 106/kg (1.30–33.7). Median ALC-15 was 190 (0–254) cells/ul, median ALC-30 was 1000 (60 to 5590) cells/ul and ALC-60 was 1290 (50–6570). There were 28% of patients in complete remission (CR) & 67% in partial remission (PR) following ASCT. On Multivariate analysis: ALC-30 was significantly associated with OS. Although there was higher PFS with higher lymphocyte count, the difference was not statistically significant. Other known prognostic factors such as ISS staging, PC at diagnosis, age at transplant and CR response following ASCT were also significantly correlated with OS & PFS. Survival analysis: Median OS was 64 (0.2 to 175) months and PFS 32 (1.7 to 175) months following PBSCT. In patients with ALC-30 &gt;500 cells/ul median OS was 80 months and 53 months in patients with ALC-30 &lt; 500 cells/ul (P= 0.0147). Fig 1: Overall survival following ASCT in months Fig 1:. Overall survival following ASCT in months PFS was 43 months in patients with ALC-30 &gt; 500 cells/ul and 31 months in patients with ALC-30 &lt; 500 cells/ul (P=0.39). Median ALC-30 was 1309 cells/ul in patients who were alive at last follow up while median ALC-30 was 879 cells/ul in patients who were deceased (P=0.0072) and in most of the patients (35/45, 77%) progressive disease was responsible for their demise. There was no significant correlation between CD34+ stem cells dose and lymphocyte dose in autograft with ALC-30 recovery (P=0.26). Conclusions: ALC-30 was an independent prognostic indicator of OS following ASCT in patients with multiple myeloma. There was trend for longer PFS in patients with ALC-30 &gt;500 cells/ul, although the difference was not statistically significant. This may be due small sample size and needs to be evaluated further in prospective study. We could not find a correlation between lymphocyte dose or CD34 dose in autograft with ALC-30 recovery. Lower ISS stage, less extensive marrow infiltration at diagnosis and complete response following PBSCT positively influences OS & PFS.

Allogeneic Hematopoietic Stem Cell Transplantation Cures CLL: A Retrospective Analysis from the SFGM-TC Registry.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2991-2991
Author(s):  
Mauricette Michallet ◽  
Quoc-Hung Lê ◽  
Jean-Paul Vernant ◽  
Franck E. Nicolini ◽  
Jean-Luc Harousseau ◽  
...  
Keyword(s):  
Autologous Transplantation ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Cord Blood Cell ◽  
The Status ◽  
The Impact ◽  
Long Term Survivors

Abstract This retrospective study concerned 471 B-CLL patients registered in the SFGM-TC registry from Apr 1,984 to Feb 2,005, who underwent either autologous transplantation (n=313, 138 F and 175 M, median age = 54, 236 PBSC and 77 BM) or allogeneic transplantation (n=158, 78 F and 80 M, median age = 49, 76 PBSC, 81 BM and 1 cord blood cell transplant from 17 related and 141 unrelated donors). Among alloT patients, 50 were ABO incompatible and 70 sex-mismatched. The median interval diagnosis-transplantation was 32 months for autoT and 51 months for alloT. Just before conditioning 302 autoT and 143 alloT were evaluated for the disease status: 100 and 26 patients were in CR, 170 and 55 were in PR, 4 and 13 in stable disease (SD), 28 and 49 in progressive disease (PD) for autoT and alloT respectively. Among alloT patients, 73 received reduced intensity conditioning (RIC) and 85 standard conditioning (72 Cyt+TBI, 33 Fluda+TBI, 23 Fluda+Bu+ATG, 8 Cyt+Bu and 21 other). Before autoT the conditioning consisted of 224 Cyt+TBI, 45 BEAM and 44 other. After alloT, 71 patients developed an aGVHD ≥ grade II and 60 developed a cGVHD (25 limited and 35 extensive). The non-relapse mortality at 1 year was 29%. With a mean follow-up of 28 months for autoT and 40 months for alloT, the probabilities of 3-year, 5-year and 8-year overall survival were 80%, 66%, 45.5% after autoT and 52%, 48% and 35% after alloT respectively. An analysis aimed to determine the percentage of long-term survivors, or patients censored on the final plateau of survival curves was performed on alloT and autoT groups. A mixture model, gfcure with Splus statistical package determined the percentages of long-term survivors and its adequacy was verified graphically. The percentage of long-term survivors for the autoT group was 1.2%, with a mean survival length for uncured population of 160 months. Fig A shows that both curves were close and consequently shows good adequacy and the absence of a final plateau. The percentage of long-term survivors for alloT was 34.03% (figure1). Fig B shows rather good adequacy. The study of the impact of usual prognosis factors (age, time diagnosis-transplant, sex match, HLA match, CMV status, type of conditioning, BM or PBSC, ABO compatibility and disease status before transplantation) on the percentage of long-term survivors showed that only the status of disease at transplant had a significant impact: (CR vs SD or PD, HR: 0.11 [0.02–0.5] p=0.01 and PR vs SD or PD, HR: 0.30 [0.09–0.96] p=0.04). This study pointed out the possibility of curing B-CLL patients who responded to conventional chemotherapy with allogeneic transplantation rather than with autologous transplantation. Figure Figure Figure Figure

Safety and Efficacy of Bortezomib (VELCADE™) in 104 Patients with Relapsed and/or Refractory Multiple Myeloma Who Have Received at Least Two Previous Lines of Therapy: Impact of Cytogenetics on Response from a Canadian Cohort.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5118-5118
Author(s):  
Joseph R. Mikhael ◽  
Donna E. Reece ◽  
Andrew Belch ◽  
Nizar J. Bahlis ◽  
Deepa Sharma
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Poor Prognosis ◽  
Progressive Disease ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
M Protein ◽  
Cytogenetic Abnormalities ◽  
Refractory Multiple Myeloma ◽  
The Impact

Abstract Background: Bortezomib (VELCADE™) is a reversible proteasome inhibitor that has been shown to be safe and efficacious in patients (pts) with relapsed and/or refractory multiple myeloma (MM) using a dose of 1.3 mg/m2 on days 1, 4, 8 & 11 of a 21-day cycle. Certain cytogenetic abnormalities are associated with poor prognosis in MM, including deletion 13, t(4;14) and the p53 deletion.(Stewart et al, JCO2005; 23(26):6339–44). Bortezomib has demonstrated the ability to overcome the poor prognosis associated with deletion 13 (Jagannath, JCO2005; 23(16S) 6501). The impact of bortezomib on a broader range of cytogenetic abnormalities, such as t(4;14) has yet to be determined. Methods: In this multicentre, open-label, non-randomized, phase 3b study, pts with MM across 13 centres in Canada, who had received at least 2 previous lines of therapy and who were refractory to or had relapsed after their last therapy were enrolled. Pts received up to eight 3-week cycles of bortezomib on days 1, 4, 8 & 11. Dexamethasone 20 mg PO was administered on each day of and day after bortezomib administration if the pts either experienced progressive disease after receiving at least 2 treatment cycles of bortezomib or had no change in disease status from baseline after receiving at least 4 treatment cycles of bortezomib. Results: 104 pts were enrolled; the mean age in this cohort was 60.7 years, and 65 (62.5%) were male. Approximately 30% of pts had a Karnofsky performance status of 70 or less at baseline. 71 pts (68.3%) had received prior thalidomide therapy, 32 (30.8%) had received a prior autotransplant and 4 (3.8%) had received prior bortezomib treatment. 74 (71.2%) received 3 or more lines of prior MM therapy. During the study, mean number of bortezomib cycles completed was 4.6 (range, 0–11 cycles), and the number of pts that completed 8 cycles of therapy was 36 (34.6%). 15.2% of pts received dexamethasone at cycle 3 and 19.2% at cycle 5. Cytogenetic analysis was performed on approximately half of the pts. Response data for cycle 5 is currently available for 69/99 (69.7%) of evaluable pts (see Table 1). Overall, 76.9% of the pts experienced Grade 3 & 4 adverse events. Safety profile observed is similar to past trial results with bortezomib. Conclusion: In this large Canadian cohort of extensively pre-treated patients with mulitple myeloma, bortezomib demonstrated good response, consistent with previous studies. Analysis correlating cytogenetic profile and response rate is ongoing and will be available at the time of conference. In addition, a detailed safety analysis and impact of prior treatment on response will be analyzed and made available at the time of conference. Table 1. Response to Bortezomib Category of Response* No. of Patients (%) *Modified SWOG: CR 100% M-protein reduction; R 75–99%; PR 50–74%; MR 25–49%; SD<25%, PD increasing M-protein Any Response (CR + VGPR + PR + MR) 47 (68.1) ---Complete Response (CR) + Very Good Partial Response (VGPR) ---22 (31.9) ---Partial Response (PR) + Minimal Response (MR) ---25 (36.2) Stable Disease 10 (14.5) Progressive Disease 12 (17.4)

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