scholarly journals A Comparative Outcome Analysis of COVID-19 and Influenza Infection in Patients with Hematological Malignancies

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2286-2286
Author(s):  
Susanne Ghandili ◽  
Christian Niederwieser ◽  
Katja Weisel ◽  
Carsten Bokemeyer ◽  
Walter Fiedler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Hematological Malignancies ◽  
Negative Impact ◽  
Medical Council ◽  
Concomitant Disease

Abstract Introduction: Patients with hematological malignancies and concomitant SARS-CoV-2 infection suffer from a more severe course of their infection than patients without underlying concomitant disease. Similar observations have been made for concomitant influenza infections. The aim of this retrospective study is to compare the clinical courses of COVID-19 and seasonal influenza in patients with hematological malignancies. Methods: In this retrospective, single center analysis all patients with hematological malignancies aged 18 years and older were included with a laboratory confirmed SARS-CoV-2 or influenza A or B infection who were admitted or were already under treatment at the Department of Oncology and Hematology or at the Department of Stem Cell Transplantation at the University Medical Center Hamburg-Eppendorf, Germany, between January 2012 and January 2021. Primary and secondary endpoints of this study are the rate of acute respiratory distress syndrome (ARDS) and virus-associated 30- and 90-day mortalities. The retrospective data collection was performed in accordance with local legal requirements and was reviewed and approved by the Ethics Committee of the Medical Council of Hamburg. Results: A total of 79 patients were included in this study. 29 patients had laboratory confirmed SARS-CoV-2 infection and 50 patients had influenza A or B infection. 69% in the COVID-19 group and 68% in the influenza group were male. Median age in the COVID-19 group were 59 years vs 58.5 years in the influenza group. Distribution of hematological malignancies in the COVID-19 group was as follows: 59% had acute leukemia (AL), 24% malignant lymphoma, 14% multiple myeloma (MM) and 3% myelodysplastic syndrome (MDS). 89% of the patients with concomitant SARS-CoV-2 diagnosis were currently under treatment with chemotherapy, CD20 or CD38 antibody-therapy, underwent allogeneic stem cell transplantation (SCT) or received CAR-T-cells shortly before (< 2 months) or during SARS-CoV-2 positivity. In the influenza group, 60% had AL, 8% lymphoma, 24% MM and 8% MDS or myeloproliferative neoplasm. 84% of these patients were under treatment with chemotherapy, CD33-, CD38- or SLAMF7-directed antibodies or underwent allogeneic SCT shortly before or during infection with seasonal influenza. At the time of infection, 41% of all SARS-CoV-2 positive patients were in refractory or relapsed setting compared to 42% in the influenza group whereas 28% in the COVID-19 and 36% in the influenza cohort were in complete remission. At the time of SARS-CoV-2 detection 38% of patients had grade IV neutropenia (defined as neutrophil count <0.5 x 10 9/L) with a median duration of 3.5 days which is comparable to 33% of patients and a median neutropenia duration of three days in the influenza group. The incidence of ARDS was significantly higher in the COVID-19 group compared to the influenza group (48% vs. 14%, p = 0.001). Furthermore, virus infection related 30-day and 90-day mortality was significantly higher in the COVID-19 group (28% vs. 8%, p = 0.026 and 41% vs. 12%, p = 0.005). In the COVID-19 group, a duration of aplasia ≥ 7 days had no negative impact on 90-day mortality or development of an ARDS (p = 0.599 and 0.982 respectively) whereas in the patients infected with influenza A or B, an aplasia ≥ 7 days had a negative impact on 90-day mortality and development of ARDS (p < 0.001 each). Conclusion: Based on our results, we conclude that comparable to the general population, infections with SARS-CoV-2 result in a significantly higher rate of ARDS and a significantly higher 30- and 90-day mortality compared to influenza A or B infections in patients with underlying hematological malignancies. Disclosures Weisel: Adaptive: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding. Bokemeyer: Gilead Sciences: Research Funding; Bayer Schering Pharma: Consultancy; Merck Serono: Consultancy, Other: Travel accomodation ; AOK Health insurance: Consultancy; Alexion Pharmaceuticals: Research Funding; Agile Therapeutics: Research Funding; ADC Therapeutics: Research Funding; Abbvie: Research Funding; GSO: Consultancy; Lilly/ImClone: Consultancy; Amgen: Research Funding; Apellis Pharmaceuticals: Research Funding; Astellas: Research Funding; BerGenBio: Research Funding; Blueprint Medicine: Research Funding; Boehringer Ingelheim: Research Funding; Celgene: Research Funding; Daiichi Sankyo: Research Funding; Eisai: Research Funding; Gylcotope GmbH: Research Funding; GlaxoSmithKline: Research Funding; Inside: Research Funding; IO Biotech: Research Funding; Isofol Medical: Research Funding; Janssen-Cilag: Research Funding; Sanofi: Consultancy, Honoraria, Other: Travel accomodation; Merck KGaA: Honoraria; Roche: Honoraria, Research Funding; Merck Sharp Dohme: Consultancy, Honoraria; AstraZeneca: Honoraria, Research Funding; BMS: Honoraria, Other: Travel accomodation, Research Funding; Bayer: Honoraria, Research Funding; Karyopharm Therapeutics: Research Funding; Lilly: Research Funding; Millenium: Research Funding; MSD: Research Funding; Nektar: Research Funding; Rafael Pharmaceuticals: Research Funding; Springworks Therapeutics: Research Funding; Taiho Pharmaceutical: Research Funding; Pfizer: Other. Fiedler: Novartis: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Daiichi Sanyko: Consultancy, Other: Meeting attendance, Preparation of information material; Stemline: Consultancy; Servier: Consultancy, Other: Meeting attendance, Preparation of information material; MorphoSys: Consultancy, Honoraria; Jazz: Consultancy, Honoraria, Other: Meeting attendance, Preparation of information material; Celgene: Consultancy, Honoraria; Ariad/Incyte: Honoraria; Amgen: Consultancy, Honoraria, Other: Meeting attendance, Preparation of information material, Patents & Royalties, Research Funding; Abbvie: Consultancy, Honoraria, Other: Meeting attendance, Preparation of information material. Modemann: Teva: Other: Travel accomodation; Novartis: Other: Travel accomodation; Jazz Pharmaceuticals: Other: Travel accomodation; Gilead: Other: Travel accomodation; Incyte: Other: Travel accomodation; Servier: Honoraria, Other: Travel accomodation; Pfizer: Other: Travel accomodation; Amgen: Other: Travel accomodation; Daiichi Sankyo: Research Funding; Abbvie: Honoraria, Other: Travel accomodation.

Allogeneic Hematopoietic Stem Cell Transplantation for CLL: Eradication of Specific FISH Abnormalities with Relation to Gvhd and Transplant Outcomes.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3465-3465
Author(s):  
Cynthia Toze ◽  
Chinmay B. Dalal ◽  
Tanya L. Gillan ◽  
Thomas J. Nevill ◽  
Michael J. Barnett ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Research Funding ◽  
Negative Impact ◽  
Dose Intensity ◽  
P Value ◽  
Hematopoietic Stem

Abstract Abstract 3465 Multiple studies have demonstrated the curative potential of allogeneic hematopoietic stem cell transplantation (allo HSCT) for CLL, with a clear and strong role for graft vs. leukemia and a less certain role for other factors including dose intensity. It is also known that FISH abnormalities (abn) are prognostic for CLL. The ability and timing of SCT to eradicate CLL in specific FISH categories, and the relationship of this clearance to onset of gvhd has not been clarified. In order to ascertain factors related to outcomes including achievement of CR, clearance of FISH abN, NRM, relapse/progression (REL) and survival, patients (pts) proceeding to allo HSCT at the Leukemia/BMT Program of BC with CLL (n=49 consecutive, 1991–2009) were studied with the use of prospective databases. HSCT Comorbidity index (Sorror) (CoI) was calculated for all pts. FISH was performed pre and post SCT in 35 and 33 pts respectively. Chimerism was performed for all pts not receiving myeloablative (MA) regimens. Gender was F:M 16:33 for pts, 15:34 donor (dn). Median (med) age at SCT was 54 yrs (32-68) for pts; 45 (19-76) yrs for dn. Max stage was Rai advanced (III/IV) in 32 (65%). 30 of 45 pts (67%) who had received prior fludarabine (flu) were flu refractory (REF); 26 (53%) were REF to their last pre-SCT therapy (tx). Med number of prior tx was 3 (1-14). CoI was 0 in 25 (50%), 1 or 2 in 17 (35%), and 3 or more in 7 pts (15%). Conditioning was MA (Cy/TBI) in 22 (45%), and reduced-intensity (RIC) in 27 (55%), consisting of flu/cy in 16 (33%), and flu/bu +/− campath (for UD only, n=9) in 11 (22%) pts. Dn was UD in 20 (41%), and HLA-mismatched (mm) in 12 (25%). PB was used for most pts (38, 78%). GVHD prophylaxis was CSP/MTX for the majority (47, 96%). With med post SCT follow-up (FU) of 5 yrs (0.2-15) 31 of 49 pts are alive. Med FU (range) from dx is 11.6 yrs (3 - 35). 18 are deceased at a med of 292 days (39 days - 5.7 yrs) post SCT, 9 with NRM and 9 with REL. All pts who died with REL had either del 17p or 11q, as did 3 of 9 pts with NRM. CR has been achieved in 33 pts, a med of 103 days (range 28 days to 5.4 yrs) post SCT, and 69 days post earliest onset of gvhd. 30 pts with CR did not REL, 3 did; 3 pts without CR have progressed, and 13 pts have not achieved CR to date but do not have progressive CLL. DLI was administered in 8 pts, a med of 154 days post SCT (86-710), resulting in CR for 6 of these 8 pts. Pre-SCT FISH abN (n, % of pts) included: del 13q (20, 57%); +12 (7, 20%); del 11q (16, 46%) and del 17p (10, 29%). 2 of 32 pt with FISH abN cleared these pre and 17 post SCT at a med of 149 days (36 days to 3.7 yrs). All pts who failed to clear FISH abN had del 17p (n=8) or 11q (n=4) with the exception of 1 pt who had del 13q and graft failure. KM estimate of OS is 63% at 2 yr, 55% at 5 yr and beyond. Factors predictive for OS include (p value): CoI <3 (0.02), FISH rank (Dohner) (0.004), achievement of CR post SCT (0.002), chimerism >90% on all tests (0.01) and clearance of FISH abN post SCT (0.04). Importantly, age of pt and dn, UD, MA vs RIC, HLA mm, sensitivity to fludarabine and last tx did not affect OS. AGVHD gr 3–4 (but not gr 0–2 or CGVHD) had negative impact on OS (0.004). Studies are ongoing to evaluate the role of HSCT timing, intensity of conditioning and gvhd in the eradication of CLL in the FISH subgroups. Specific tailoring of transplant intensity and manipulation of graft vs leukemia effects may be required for individual patients in particular to improve outcomes for poor risk patients with del 17p, and to minimize risk for patients with better prognosis. Disclosures: Toze: Hoffman La Roche: Consultancy, Honoraria, Research Funding; Genzyme: Honoraria, Research Funding; Glaxo Smith Kline: Honoraria. Sutherland:Celgene: Honoraria; Orthobiotech: Honoraria.

scholarly journals What is known about palliative care in adult patients with allogeneic stem cell transplantation (allo-SCT)?

2021 ◽  
Author(s):  
Steffen T. Simon ◽  
Anne Pralong ◽  
Michael Hallek ◽  
Christoph Scheid ◽  
Udo Holtick ◽  
...  
Keyword(s):  
Palliative Care ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Negative Impact ◽  
Chronic Gvhd ◽  
Care Needs ◽  
Post Transplantation

AbstractPatients undergoing allogeneic stem cell transplantation (allo-SCT) are given a real chance of cure, but at the same time are confronted with a considerable risk of mortality and of severe long-term impediments. This narrative, non-systematic literature review aims to describe the supportive and palliative care needs of allo-SCT recipients, including long-term survivors or those relapsing or dying after transplantation. It also evaluates the feasibility and effectivity of integrating palliative care early in transplant procedures. In this appraisal of available literature, the main findings relate to symptoms like fatigue and psychological distress, which appear to be very common in the whole allo-SCT trajectory and might even persist many years post-transplantation. Chronic GvHD has a major negative impact on quality of life. Overall, there is a paucity of research on further issues in the context of allo-SCT, like the distress related to the frequently unpredictable post-transplant trajectory and prognosis, as well as the end-of-life phase. First randomized controlled results support the effectiveness of early integration of specialized palliative care expertise into transplant algorithms. Barriers to this implementation are discussed.

scholarly journals Outcome of Autologous Stem Cell Transplantation in Waldenström's Macroglobulinemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2149-2149
Author(s):  
Romil Patel ◽  
Neeraj Y Saini ◽  
Ankur Varma ◽  
Omar Hasan ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Advisory Committees ◽  
First Remission ◽  
Relapsed Disease

Abstract Introduction: The role of autologous hematopoietic stem cell transplantation (auto-HCT) in the management of patients with Waldenström Macroglobulinemia (WM), a rare, indolent lymphoma, has not been established. We had previously published our experience with auto-HCT in a small cohort of WM patients1. Here, we present an updated analysis of auto-HCT with a larger cohort of WM patients. Methods and study population: The study cohort was comprised of 29 patients who underwent high-dose chemotherapy and auto-HCT at MD Anderson Cancer Center (MDACC). The Kaplan-Meier method was used to create survival curves. Overall survival (OS) was defined as the duration from date of transplant to death or last date of follow-up in living patients. Progression-free survival (PFS) was defined as the duration from date of transplant to either progressive disease or death, whichever occurred first. Results: Median age at auto-HCT was 60 (range, 43-75 years). Eight patients (28%) had concurrent light chain amyloidosis (AL). Of the five patients who had MYD88 testing completed, 3 were positive for the MYD88 mutation. Additionally, of these 3 patients, 2 were also positive for CXCR4 mutation. Patients received a median of 2 lines (range 1-6) of therapy prior to auto-HCT; 3(10%) patients had primary refractory disease, 8(28%) were in first remission, and 18 (62%) had relapsed disease. Median time from transplant to last follow-up for the surviving patients was 5.3 years. Preparative regimens received by the patients were: Melphalan (n=20), BEAM-R (n=2), Busulfan/Melphalan (n=1), Cyclophosphomaide/Etoposide/total body irradiation (n=1), Thiotepa/Busulfan/Cyclophosphamide (n=1), and Carmustine/Thiotepa (n=1). Three patients further went on to receive allogeneic transplant either after relapse from auto-HCT or due to disease transformation to aggressive lymphoma. Twenty-eight patients achieved engraftment with a median time to neutrophil engraftment of 11 days (range, 10-15 days). One patient suffered primary graft failure due to progression of disease and died 84 days after transplant. Non-relapse mortality was 3.4% at 1 year. All patients were eligible for response evaluation. The median OS from diagnosis was 12.2 years. Overall response rate was 96%: complete response (n=8, 27.6%), very good partial response (n=5, 17.3%), partial response (n=15, 51.7%), and progressive disease (n=1, 3.4%). PFS and OS at 5 years were 43.3% and 62.9%, respectively. Median PFS and OS from auto-HCT were 4.1 and 7.3 years (Fig. 1A). The median OS from auto-HCT in first remission + primary refractory and relapsed disease was 8.2 years and 4.1 years, respectively.16 patients were alive at the time of censoring while 13 patients had died. Causes of death include relapsed disease (n=6), secondary malignancy (n=2), infection (n=1), chronic graft-versus-host disease (n=1), and unknown (n=3). 8 patients (28%) were positive for concurrent AL amyloidosis. The sites of amyloid involvement were kidneys (n=2), lungs (n=1), bone marrow (n=1), heart(n=1), lymph nodes(n=1), gastrointestinal tract (n=1) and subcutaneous fat aspirate(n=5). The median overall survival for patients with amyloid involvement (n=8) was 12 years. On univariate analyses, the number of chemotherapy regimens prior to transplant (≤ 2 vs >2 lines) was the strongest predictor of overall survival (p=0.03, HR 0.3, CI: 0.09-0.9, log-rank) and PFS (p=0.001, HR 0.24, CI: 0.07-0.85, log-rank). The median PFS in patients with ≤ 2 lines and > 2 lines of therapy was 71 months versus 19 months, respectively (Fig. 1B). Conclusion: Auto-HCT is safe and feasible in selected patients with WM, with a high response rate and durable remission even in patients with relapsed or refractory disease. References: Krina Patel et.al. Autologous Stem Cell Transplantation in Waldenstrom's Macroglobulinemia. Blood 2012 120:4533; Disclosures Thomas: Celgene: Research Funding; Bristol Myers Squibb Inc.: Research Funding; Acerta Pharma: Research Funding; Array Pharma: Research Funding; Amgen Inc: Research Funding. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Orlowski:Takeda: Consultancy; Celgene: Consultancy; Spectrum Pharma: Research Funding; Janssen: Consultancy; Kite Pharma: Consultancy; Sanofi-Aventis: Consultancy; BioTheryX: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Champlin:Otsuka: Research Funding; Sanofi: Research Funding. Patel:Poseida Therapeutics, Inc.: Research Funding; Takeda: Research Funding; Abbvie: Research Funding; Celgene: Research Funding.

scholarly journals The Prognostic Impact of the Diagnostic CD34+/CD38- Cell Burden and Expression of the Stem Cell Marker GPR56 after Stem Cell Transplantation Depends on the AML Origin

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 323-323
Author(s):  
Madlen Jentzsch ◽  
Marius Bill ◽  
Juliane Grimm ◽  
Dominic Brauer ◽  
Julia Schulz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Solid Tumors ◽  
Cell Transplantation ◽  
Research Funding ◽  
De Novo ◽  
Prognostic Impact ◽  
Expression Levels ◽  
Rheumatologic Diseases ◽  
De Novo Aml

Introduction: Acute myeloid leukemia (AML) developing secondary after other hematologic diseases, or therapy related after cytotoxic treatment for solid tumors or rheumatologic diseases (s/tAML) is clinically, genetically & prognostically distinct from de novo diseases. Data indicate that s/tAML patients (pts) have inferior outcome compared to de novo cases after chemotherapy & therefore often require consolidation therapy using allogeneic stem cell transplantation (HSCT). Leukemic stem cells (LSC) initiate & maintain AML. They are also believed to exist within the CD34+/CD38- &/or high GPR56 expressing bone marrow (BM) population, which have been shown to impact adversely on outcome. The prognostic impact of LSC markers in de novovs s/tAML after HSCT with non-myeloablative conditioning intensity - where the therapeutic approach also relies on immunological graft-versus-leukemia effects - is unknown. Methods: We analyzed 379 AML pts who received an allogeneic peripheral blood HSCT in complete remission (CR, 82%) or CR with incomplete peripheral recovery (CRi, 18%) between 1999 & 2018 after non-myeloablative (3x30 mg/m2 Fludarabine & 2 Gy total body irradiation) conditioning. At diagnosis, cytogenetic & flow cytometric analyses were performed centrally. For pts with pre-treatment BM available the mutation status of CEBPA, NPM1 & presence of FLT3-ITD by fragment analyses as well as expression levels of GPR56 by qPCR were assessed. Using a next-generation targeted amplicon sequencing approach we analyzed a panel comprising 54 recurrently mutated (mut) genes in myeloid malignancies on the MiSeq platform (Illumina). Median follow up after HSCT was 3.7 years. Results: 229 pts (60%) had de novo & 150 pts (40%) had AML secondary to myelodysplastic syndrome (MDS, n=82), myeloproliferative neoplasm (MPN, n=22) or MDS/MPN (n=10), or therapy related after Non-Hodgkin lymphoma (n=9), solid tumors (n=25) or rheumatologic diseases (n=2). At diagnosis, s/tAML pts had lower white blood counts (P=.03), lower blasts in BM (P&lt;.001) or blood (P=.007) & a higher BM CD34+/CD38- cell burden (P=.01) & GPR56 expression (P=.04). They also had worse European LeukemiaNet risk (P=.007), were less likely to have a normal karyotype by trend (P=.06), to have a core binding factor AML (P=.02), to be NPM1mut (P=.003), DNMT3Amut (P=.03) & to harbor a FLT3-ITD (P=.002) but more likely to be JAK2mut (P&lt;.001). Comparing pts with s/tAML vsde novo AML, there was no significant different cumulative incidence of relapse (CIR, P=.85) or overall survival (OS, P=.29). Next, we evaluated the prognostic impact of the LSC-associated populations in pts with de novo or s/tAML separately. In pts with de novo AML, we observed a significantly higher CIR & shorter OS for pts harboring a high CD34+/CD38- cell burden (high vs low, 6% cut, P=.006 [Fig. 1A] & P=.003) & a higher CIR but not significantly different OS for pts with a low GPR56 expression (high vs low, median cut, P=.03 [Fig. 1B] & P=.95). Combining both parameters, we observed a stepwise higher CIR & shorter OS for pts with low expression of both variables vs pts with a low CD34+/CD38- cell burden but high GPR56 expression vs pts with a high CD34+/CD38-cell burden (P=.003 [Fig. 1C] & P=.05). In contrast, in pts with s/tAML, there was no prognostic significance of the CD34+/CD38- cell burden (CIR P=.38 [Fig. 1D] & OS P=.95), the GPR56 expression (CIR P=.64 [Fig. 1E] & OS P=.82) & both markers combined (CIR P=.57 [Fig. 1F] & OS P=.98). Also in multivariate analyses, the combination of both markers significantly impacted CIR (Hazard ratio 2.49, P&lt;.001 after adjustment for donor type) & was the only significant factor for OS (Odds Ratio 0.68, P=.04) in de novo AML but not in s/tAML. Conclusion: While there was no significantly different CIR or OS in s/tAML compared to de novo AML pts undergoing non-myeloablative HSCT we observed a significant impact on outcome for the known LSC-associated prognosticators CD34+/CD38- cell burden & GPR56 expression levels at diagnosis only in de novo AML pts. Different underlying disease biology & possibly different LSC-associated populations may be relevant for disease reoccurrence in s/tAML. Figure Disclosures Jentzsch: Novartis: Honoraria; Jazz Pharmaceuticals: Honoraria. Niederwieser:Daichii: Speakers Bureau; Cellectis: Consultancy. Platzbecker:Abbvie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Schwind:Daiichi Sankyo: Honoraria; Novartis: Honoraria, Research Funding.

scholarly journals Liposomal Daunorubicin/Cytarabine As a Bridge to Donor Lymphocyte Infusion or Allogeneic Stem Cell Transplantation for High-Risk Acute Myelogenous Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5726-5726
Author(s):  
Daulath Singh ◽  
Patrick Hagen ◽  
Nasheed Hossain ◽  
Scott E. Smith ◽  
Patrick J. Stiff ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cell Therapy ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Donor Lymphocyte Infusion ◽  
The Other ◽  
Myelogenous Leukemia ◽  
Liposomal Daunorubicin

Introduction: Liposomal daunorubicin/cytarabine (Vyxeos®) is a dual drug liposomal encapsulation of cytarabine and daunorubicin, delivering drugs at a fixed 5:1 synergistic ratio for a longer therapeutic period. Compared to standard 7+3, liposomal cytarabine/daunorubicin (lipo-cytara/dauno) patients had improved survival and remission rates in a pivotal phase III study of elder adults with high-risk acute myelogenous leukemia (AML). Furthermore, more lipo-cytara/dauno patients went to allogeneic stem cell transplantation (HCT), with lower mortality and improved survival compared to those induced with 7+3. With its enhanced pharmacokinetics, lipo-cytara/dauno may provide a potent bridge to transplant. We report our experience using lipo-cytara/dauno as a bridge to same donor lymphocyte infusion (DLI) or different donor HCT in high-risk AML. Methods: We retrospectively reviewed all patients who received lipo-cytara/dauno at our institution since the FDA approval in August 2017. Of the 21 patients who have been treated, 9 received it as a bridge to cell therapy. All patients received the drug by usual means under the FDA label. Results: The median age of the 9 patients who received lipo-cytara/dauno as a bridge to cell therapy was 59 years. Seven were male, and two were female. Patients had had 1-4 prior lines of chemotherapy (median 2) with 7 of 9 patients having received prior standard 7+3 induction (cytarabine 100-200 mg/m2 x 7 days infusion and daunorubicin 60-90 mg/m2 x 3 days). Most had adverse cytogenetics, and all 9 patients received full lipo-cytara/dauno induction (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 on Days 1, 3, and 5) as outpatient therapy [Table]. Of the 9 patients, 6 had AML with very early relapse after HCT, with median time to relapse of 4 months (range 3 to 7 months). All 6 successfully proceeded to their planned cell infusion: 5 received same donor DLI after melphalan at 140 mg/m2, and 1 underwent second HCT from a different donor with busulfan/fludarabine conditioning at Days 15-40 after lipo-cytara/dauno. Of the remaining 3, two had relapsed AML after an initial remission (one was in first complete remission (CR1) for 3 months after 7+3/midostaurin induction and the other was in CR1 for 7 months after 7+3 induction/high dose cytarabine consolidation) and one had primary refractory disease (PREF) after 7+3 and azacitidine/venetoclax induction regimens. All 3 successfully underwent first HCT at Days 15-100 days after lipo-cytara/dauno bridge. The PREF patient received fludarabine/cyclophosphamide/TBI conditioning followed by matched unrelated donor transplant. Of the 2 with relapsed AML after initial remission, one received busulfan/fludarabine/thiotepa conditioning followed by umbilical cord stem cell transplantation and the other patient received fludarabine/cyclophosphamide/TBI conditioning prior to matched related donor transplant. Six of 9 had Day 14 bone marrow biopsies after lipo-cytara/dauno: 2 were in CR, 2 had >80% cytoreduction, and 2 had similar blast count. Three with persistent disease underwent reinduction with lipo-cytara/dauno (Days 1 and 3) and proceeded straight to cell therapy after. Median days to hospitalization after outpatient lipo-cytara/dauno was 6 days (range 3 to 14 days). Four out of 9 patients remain alive. Two were very early post HCT relapses (relapsed at 3 and 6 months post-HCT), both of which are remarkably in CR at 14 and 17 months after second cell therapy. Interestingly, both had CNS relapse, which were successfully treated, and both remain alive and in remission today. The other two had relapsed AML and PREF AML and underwent first HCT after lipo-cytara/dauno bridge. They remain alive and in remission at 1 and 8 months. Conclusion: In this retrospective study, outpatient lipo-cytara/dauno as a bridge to cell therapy is feasible and effective in very high-risk AML with no other viable options. While preliminary, survival appears favorable to that reported elsewhere at 14-23% at 1 year in this poor risk group, including those with adverse cytogenetic and/or very early post-HCT relapse. Prospective multi-center trials are planned to further evaluate lipo-cytara/dauno as a bridge to DLI/HCT in those with early relapse post-HCT and in those with refractory disease, with therapy to include CNS prophylaxis. Disclosures Stiff: Gilead/Kite Pharma: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Gamida-Cell: Research Funding; Incyte: Research Funding; Cellectar: Research Funding; Unum: Research Funding. Tsai:Jazz pharmaceuticals: Speakers Bureau; Jazz pharmaceuticals: Consultancy.

scholarly journals SECOND ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES

2019 ◽  
Vol 64 (1) ◽  
pp. 35-48
Author(s):  
L. A. Kuzmina ◽  
Z. V. Konova ◽  
E. N. Parovichnikova ◽  
M. Y. Drokov ◽  
V. A. Vasilyeva ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Failure ◽  
Hematological Malignancies ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem

Background.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a standard treatment for many patients with hematological malignancies. Complications of allo-HSCT are frequently associated either with a relapse of the underlying disease or a graft failure. Second transplantation can be offered to selected patients and is seen as the only curative option. In this paper, we report the experience of managing 24 such patients, all of whom underwent a second allo-HSCT.Patients and methods.The research involved 24 patients (12 males/12 females) suffering from acute myeloid leukemia (AML, n = 14), acute lymphoblastic leukemia (ALL, n = 4), myeloproliferative disease (MPD, n = 3) and myelodysplastic syndrome (MDS, n = 3). The patients’ age ranged from 18 to 56 years, with the median age being 32 years. All the patients underwent a second allo-HSCT due to the disease relapse (n = 11) or graft failure (n = 13). 12 patients underwent a second allo-HSCT within the period of less than 6 months after the first allo-HSCT.Results.Following the second allo-HSCT, engraftment occurred in 18/24 (75 %) patients, while 3 patients demonstrated graft failure and 3 — disease progression. Out of 18 patients having engrafted, 9 (50%) died during the first 100 days after allo-HSCT as a result of severe infections or visceral toxicity. 3 more lethal outcomes were recorded in later periods due to the disease progression. The overall mortality rate after the second allo-HSCT equalled 61.5 %. The median overall survival (OS) and disease-free survival (DFS) rates were 13.5 months and 10.59 months, respectively. Three-year OS and DFS were 38.5 % and 27.6 % respectively. Significant differences in terms of OS were detected for patients with a longer interval (>6 months) between the first and second allo-HSCT. The change of a donor was not associated with a better clinical outcome.

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