Allogeneic Stem Cell Transplantation Is Associated with Prolonged Disease Control in Chemosensitive Aggressive Histology Lymphoma Patients When Done Early

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4525-4525
Author(s):  
Auro Viswabandya ◽  
Tony Panzarella ◽  
Dennis Dong Hwan Kim ◽  
Vikas Gupta ◽  
Jeffrey H. Lipton ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Advisory Committees ◽  
Aggressive Histology ◽  
Grade 3

Abstract Abstract 4525 Introduction Allogeneic stem cell transplantation (Allo-SCT) is a treatment option in aggressive histology lymphoma (AG-NHL) patients who have either failed or relapsed after autologous SCT (ASCT) or if the potential for long term disease control after ASCT is limited. There is limited data in literature regarding the long term outcome of allo-SCT in AG-NHL. Methods We did a retrospective analysis of all aggressive histology patients who underwent Allo-SCT between 1989 and 2009 at our centre. A total of 41 patients with AG-NHL [diffuse large B cell lymphoma (DLBCL) and variants, follicular lymphoma grade 3 (FL3), biopsy proven aggressive transformation of indolent lymphoma (TRIL)] underwent Allo-SCT. All patients were in a chemosensitive remission at time of transplantation. The conditioning regimen was BU-CY in the majority (36 or 88%) of patients and 3 patients had reduced intensity transplantation (RIC) with fludarabine-based regimens. GVHD prophylaxis was cyclosporine and methotrexate until 2009 and was cyclosporine and mycophenolate mofetil after that. Alemtuzumab was used in matched unrelated donor (MUD) transplants in 5 (12%) cases. Results There were 22 (54%) males and 19 (46%) females. The median age at BMT was 48 years (range: 20–65). Fifteen (37%) had DLBCL, 19 (46%) had TRIL and 7 (17%) had FL3. Fifteen (37%) patients had received 2 or less lines of chemotherapy and 26 (63%) had received more than 2 lines of therapy at time of transplantation. The median number of chemo regimens was 3 (range: 1–7). The chemotherapy regimens included prior anthracyclines in 40 (98%), prior platinum in 26 (63%) and prior mini BEAM in 19 (46%). Six (15%) patients had received Rituximab and 9 (22%) had received prior RT. Seven (17%) patients had prior ASCT. Thirty-five (85%) of patients received matched related donor transplant whereas 5 (12%) received MUD transplant. The graft source was bone marrow in 33 (80%) and peripheral blood stem cells in 8 (20%). Grade 1–2 acute GVHD was seen in 53% and grade 3–4 in 9%. Chronic GVHD was seen in 51% patients. With a median follow up of 49 months and 96 months in those who are alive, five (12%) patients have relapsed, 20 (49%) patients are alive and in remission. Non relapse mortality (NRM) was 16/41 (39%) and predominantly related to infection. The overall survival (OS) and progression free survival (PFS) of the entire cohort at 60 months was 55% (Fig-1). Patients, who had achieved CR pre-allo-SCT (compared to PR) had a statistically significantly improved PFS and OS (100% survival for those who were in CR). In multivariate analysis, number of chemotherapy regimens (≤2) was associated with improved OS (p=0.015) and presence of chronic GVHD showed a trend towards significant OS (p=0.052) Conclusions With a median follow up of 96 months in survivors, myeloablative allo-SCT is associated with durable remission in patients with chemosensitive AG-NHL. Results are less favourable in patients who have received multiple prior regimens. NRM remains a significant concern with myeloablative regimens. We believe there is a role for myeloablative regimens and research should focus on ways to reduce NRM in this setting. Disclosures: Gupta: Incyte: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.

Stem Cell Transplantation Can Provide Durable Disease Control in Blastic Plasmacytoid Dendritic Cell Neoplasia (BPDC): A Retrospective Study From the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3077-3077
Author(s):  
Sascha Dietrich ◽  
Damien Roos-Weil ◽  
Ariane Boumendil ◽  
Emanuelle Polge ◽  
Jian-Jian Luan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Nk Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Advisory Committees

Abstract Abstract 3077 Blastic plasmacytoid dendritic cell neoplasm (BPDC), formerly known as blastic NK cell lymphoma, is a rare hematopoietic malignancy preferentially involving the skin, bone marrow and lymph nodes. The overall prognosis of BPDC is dismal. Most patients show an initial response to acute leukemia-like chemotherapy, but relapses with subsequent drug resistance occur in virtually all patients resulting in a median overall survival of only 9–13 months. However, anecdotal long-term remissions have been reported in young patients who received early myeloablative allogeneic stem cell transplantation (alloSCT). We therefore performed a retrospective analysis of patients identified in the EBMT registry in order to evaluate the outcome of autologous stem cell transplantation (autoSCT) or alloSCT for BPDC. Eligible were all patients who had been registered with a diagnosis of BPDC or Blastic NK cell lymphoma and had received autologous stem cell transplantation (autoSCT) or alloSCT in 2000–2009. Centres were contacted to provide a written histopathology and immunophenotyping report and information about treatment and follow-up details. Patients who did not have a diagnostic score ≥ 2 as proposed by Garnache-Ottou et al. (BJH 2009) were excluded. RESULTS: Overall, 139 patients could be identified in the database who fulfilled the inclusion criteria (alloSCT 100, autoSCT 39). Of 74 patients for whom the requested additional information could be obtained, central review confirmed the diagnosis of BPDC in 39 patients (34 alloSCT, 5 autoSCT). The 34 patients who had undergone alloSCT had a median age of 41 years (range: 10–70 years), were transplanted from a related (n=11) or unrelated donor (n=23); received peripheral blood stem cells (n=9), bone marrow stem cells (n=19) or cord blood (n=6); and had been treated with a reduced intensity conditioning regimen (RIC, n=9) or myeloablative conditioning (MAC, n=25). Nineteen of 34 patients were transplanted in CR1. After a median follow up time of 28 months (range: 4–77+ months), 11 patients relapsed (median time to relapse: 8 months, range: 2–27 months) of whom 8 died due to disease progression. 9 patients died in the absence of relapse. No relapse occurred later than 27 months after transplant. Median disease free survival (DFS) was 15 months (range: 4–77+ months) and median overall survival (OS) was 22 months (range: 8–77+ months; Figure 1a). However, long-term remissions of up to 77 months after alloSCT could be observed. Patients allografted in CR1 tended to have a superior DFS (p=0.119) and OS (p=0.057; Figure 1b). MAC was associated with a better OS (p=0.001) which was attributable to the significantly higher non-relapse mortality (NRM) rate of patients after RIC (p=0.014), who had been significantly older (age RIC: 56 years, age MAC: 36 years, p=0.0014). The relapse rate was not different in patients after RIC and MAC, respectively. However, there was no survivor after RIC. Median age in the autoSCT group was 47 years (range: 14–62 years). Three of 5 patients were transplanted in CR1 of whom 1 patient relapsed after 8 months, 1 patient experienced treatment related mortality and 1 patient remained in CR for 28 months. The 2 remaining patients had more advanced disease at autoSCT and relapsed 4 and 8 months thereafter. CONCLUSION: AlloSCT is effective in BPDC and might provide curative potential in this otherwise incurable disease, especially when performed in CR1. However, it remains to be shown by prospective studies if the potential benefit of alloSCT in BPDC is largely due to conditioning intensity, or if there is a relevant contribution of graft-versus-leukemia activity. Disclosures: Tilly: Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau, Travel/accommodations/meeting expenses; Genentech: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding, Speakers Bureau; Pfizer: Speakers Bureau; Janssen Cilag: Speakers Bureau.

Secondary Malignancies after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4297-4297
Author(s):  
Stefan Neuburger ◽  
Philipp Hemmati ◽  
Theis Terwey ◽  
Gero Massenkeil ◽  
Bernd Dörken ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Secondary Malignancies ◽  
Extensive Disease ◽  
Immunosupressive Therapy

Abstract Introduction: Allogeneic stem cell transplantation is a curative therapeutical option for patients (pts) with hematological diseases. As result of long term survival, late complications such as secondary malignancies are emerging. Methods: Here we present a retrospective analysis of 589 pts (median age at transplantation 41 years, range 16–75, male 339, female 250) who underwent allogeneic stem cell transplantation in our institution between 1995 and 2007 (siblings n= 285, unrelated donors n= 304). Pts suffered from acute leukemia (n= 257), chronic myeloproliferative disorders (n= 120), myelodysplastic syndrome (n= 39), non-hodgkin-lymphomas (n= 41) and others (n= 132). Pts received conditioning with (n= 436) or without (n=152) 12 Gy total body irradiation (TBI). Results: Up to 2007, 283 of 589 pts (48%) died of relapse or transplant related mortality (n=135 relapse, n= 84 infection, n= 36 graft-vs-host-disease (GVHD), n= 8 organ toxicity, n= 20 others or unknown). 305 out of 589 pts (52%) had survived with a median follow-up of 40 months (range 1–144 months). 21 out of 305 pts (6,9%) developed secondary malignancies at a mean of 5,1 years (range 1–10 years) after allogeneic stem cell transplantation. Localizations of secondary malignancies were skin (n= 11 basalioma, n= 2 melanoma), gut (n= 2 adenocarcinoma of the small intestine, n= 1 coloncarcinoma), oral cavity (n= 1 squamous cell cancer) and 3 lymphomas. 17/21 pts (81%) received a myeloablative conditioning with 12 Gy TBI, 4/21 pts (19%) a reduced intensity conditioning. Acute GVHD > grade 2 and chronic GVHD extensive disease appeared in 48% and 67% respectively. Thus, these pts must be treated with prolonged immunosupressive therapy. 2/21 (9,5%) died of secondary malignancies (carcinoma of small intestine and colon) and one pts of accidential infection. Conclusion: Long term surviver of allogeneic stem cell transplantation are at increased risk of a secondary malignancies. Most of the pts received TBI-based conditioning and suffered from chronic GvHD extensive disease with consecutive immunosupressive therapy. Life-long follow-up will be needed to detect secondary malignancies in early stage of disease which might offer curative therapeutical options. Therefore, in our institution all pts undergo annual skin screening program and are sensitized for possibility of secondary malignancies late after transplantation.

scholarly journals High Rate of Long Term Complete Remission for Patients with Chronic Lymphocytic Leukemia (CLL) Who Relapse after Allogeneic Stem Cell Transplantation and Receive Salvage with Donor Lymphocyte Infusions (DLI)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5860-5860
Author(s):  
Alan P Skarbnik ◽  
Mary E DiLorenzo ◽  
Tracy Andrews ◽  
Phyllis McKiernan ◽  
Scott D. Rowley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Advisory Committees

Abstract Background: Allogeneic stem cell transplantation (SCT) remains the only curative option for CLL, in part due to allogeneic graft-vs-leukemia effect (GVL), which can lead to complete suppression of the CLL clone (Schetelig et al, JCO 2003). Management of post-SCT relapse remains challenging, and DLI has been successfully used as salvage, due to its potential to induce GVL (Delgado et al, Blood 2009). We evaluated outcomes of SCT for patients (pts) with a diagnosis of CLL transplanted at our center. Methods: 36 consecutive pts transplanted between 2004 and 2015 were reviewed. Kaplan Meier survival curves were produced to examine overall survival (OS), time to progression (TTP) and post-DLI survival. Univariate Cox Proportionate hazard models were also estimated to assess the impact of pt characteristics on the risk of survival and progression. Bivariate frequencies with Fisher exact tests, correlation analysis, and independent samples t-tests were performed to test associations across outcomes. Results: Sample was 72% male. Median age at time of SCT was 57 yo (range 42-74). Pts had a median time of 70 months (mos) between diagnosis (Dx) of CLL and SCT. Median follow-up post-SCT was 32 mos (range 1-118). Of the 30 pts with known disease status at the time of SCT, 16.7% were in complete remission (CR), 20% had stable disease (SD), 50% were in partial remission (PR) and 13.3% had progressive disease (PD). Median number of lines of therapy pre-SCT was 3 (range 1-8). Thirteen pts (36%) were refractory to their first line of therapy. 10 pts (27.8%) had del(17p), 11 pts (30.6%) had del(11q) and 8 pts (22.2%) had complex cytogenetics. Most patients (72%) received pre-SCT conditioning with FCR (Khouri et al, Exp Hematol 2004). 16 pts (44.4%) received rATG as part of their conditioning regimen. Graft-vs-host disease (GVHD) prophylaxis consisted of methotrexate and tacrolimus. 20 (55.6%) pts had acute GVHD and 19 (52.8%) had chronic GVHD. 5 (13.8%) pts had grade 3/4 acute GVHD and 1 (2.7%) had extensive chronic GVHD. When comparing pts who received SCT from unrelated donors (MUD, 24 pts) vs sibling donors (sib, 10 pts) there were no differences in rates of GVHD, disease progression or overall survival. Twenty-seven pts (75%) were in CR at first disease evaluation after SCT (CR conversion rate of 58.3%) and 2 pts (5.5%) had PD. On follow-up, another 15 pts (41.7%) presented PD. Median TTP was 14 months, with only 3 pts relapsing after 2 years from SCT. Eight pts who had PD and one patient who had a PR post-SCT received short-term anti-CLL therapy for disease debulking, followed by DLI. Six (66.6%) out of the 9 pts who received DLI achieved CR and are currently alive and in CR. Median follow-up post-DLI was 43 months and median duration of response to DLI was 47 mos (range 6-85 mos). Ultimately, 13 (36.1%) pts died, 8 (22.2%) were lost to follow-up, and 15 (41.7%) were alive at last contact. Disease progression was the most common cause of death (5 pts, 13.9%). Transplant-related mortality (TRM) was 13.9% (3 deaths due to infection, 2 deaths due to chronic GVHD). Only 2 deaths (5.5%) occurred during the first 100 days post-SCT, both due to infection. No deaths occurred due to acute GVHD. Median OS was 84 months. PFS (not accounting for pts who relapsed post-SCT but achieved CR with DLI) was 58% in the first year and 25% at five years. The median PFS was 19 months. Univariate and multivariate analysis of pre-SCT pt characteristics (age, time from Dx to SCT, number of therapies, stage, presence of adenopathy, MUD vs sib donor, cytogenetic abnormalities, ABO mismatch, disease status at SCT) did not show any statistically significant correlation with OS, PFS or GVHD rates. Conclusion: SCT remains the only curative option for CLL. Our experience shows that pts may achieve long-term survival with this approach. TRM was low (13.8%) and rates of acute and chronic GVHD were compatible with previous reports (Sorror et al, JCO 2005; Dreger et al, Blood 2010). Type of donor (MUD vs sib) did not impact outcomes, suggesting that patients without a matched sibling should not be denied transplantation if a MUD is available. Although 47% of the patients eventually progressed after transplantation, 66% of patients who received DLI for salvage were able to achieve CR and remain progression-free for a prolonged period of time, underlining the importance of the GVL effect. Most relapses occurred within the first 2 years post SCT and late relapses were rare. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures Skarbnik: Gilead Sciences: Speakers Bureau; Seattle Genetics: Speakers Bureau; Genentech: Speakers Bureau; Abbvie: Consultancy; Pharmacyclics: Consultancy. Vesole:Celgene: Speakers Bureau; Takeda: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau. Goy:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Writing support, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Feldman:Pharmacyclics: Speakers Bureau; Celgene: Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau. Leslie:Seattle Genetics: Speakers Bureau; Celgene: Speakers Bureau. Leslie:Seattle Genetics: Speakers Bureau; Celgene: Speakers Bureau.

scholarly journals Reduced Intensity Stem Cell Transplantation for Accelerated-Phase Myelofibrosis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 314-314
Author(s):  
Nico Gagelmann ◽  
Anita Badbaran ◽  
Markus Ditschkowski ◽  
Victoria Panagiota ◽  
Bruno Cassinat ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Continuous Variable ◽  
Advisory Committees ◽  
Reduced Intensity

Abstract Background Circulating peripheral blasts ≥1% have long been considered an unfavorable feature for patients with primary myelofibrosis. Recent findings (Masarova et al. Cancer 2020) suggested more differentiated impact of blasts on outcome. However, accelerated-phase (AP) myelofibrosis, which is currently defined by circulating blasts 10-19%, usually confers worse outcome. The outcome of allogeneic stem cell transplantation for AP myelofibrosis has not been evaluated yet. Patients and Methods Thirty-five out of 349 patients with primary or secondary myelofibrosis undergoing reduced intensity allogeneic stem cell transplantation were reported as AP (10-19% blasts) at time of transplantation. Outcome of these patients was compared to patients with circulating blasts: 0% (n=135), 1-4% (n=146), and 5-9% (n=33). Conditioning consisted of busulfan/fludarabine, fludarabine/melphalan, or fludarabine/TBI2Gy. Results Characteristics. The median blast percentage in the AP group was 14% (10-19%). More patients in the AP group appeared to have secondary myelofibrosis (40%) compared with patients with the 0% blasts (21%), the 1-4% blasts (31%), and 5-9% blasts group (30%, P=0.08). The median hemoglobin levels decreased with blast group: 9.7g/dl (0%), 9.5g/dl (1-4%), 9.4g/dl (5-9%), and 9.0g/dl (AP). In contrast, median leukocyte counts appeared to be increased: 7.2, 9.5, 16.9, and 13.6 x 10 9/l, respectively. More patients in the AP group presented with constitutional symptoms (71%). There was no difference in frequency of driver mutations (P=0.57) and presence of high-risk mutation profile (defined as ASXL1, SRSF2, IDH1/2, EZH2; P=0.93). Most patients in each group received matched unrelated donor transplants (P=0.61). Survival. The median follow-up of all patients was 6 years. Follow-up was similar across the 4 groups (P=0.30). 5-year overall survival (95% confidence interval) according to blast group was 66% (58-73%) for the 0%, 62% (53-71%) for the 1-4%, 66% (50-81%) for the 5-9%, and 68% (53-83%) for the AP group (P=0.92). Median overall survival was not reached for all groups, except for 1-4% blasts group (17.1 years). 10-year long-term follow-up showed survival rates of 64% for the 0%, 58% for the 1-4%, 66% for the 5-9%, and 68% for the AP group. In terms of relapse-free survival, 5-year outcome was comparable (P=0.95) showing 57% (48-66%) for the 0%, 52% (43-60%) for the 1-4%, 55% (37-73%) for the 5-9%, and 52% (34-69%) for the AP group. Median relapse-free survival was 7.9 years, 5.7 years, 6.5 years, and 9.2 years, respectively. Taking blasts as continuous variable in spline function analyses on survival, no significant effect was identified overall, while after 15% blasts, risk for death appeared to increase consistently. Non-relapse mortality and relapse. In terms of non-relapse mortality, no difference was found between the groups (P=0.33). 5-year outcome was 25% (19-31%) for the 0%, 33% (25-40%) for the 1-4%, 31% (15-47%) for the 5-9%, and 17% (5-30%) for the AP group. In terms of cumulative incidence of relapse, the AP group showed 5-year outcome of 31% (15-47%) compared to 18% (12-24%) for the 0%, 16% (10-22%) for the 1-4%, and 14% (1-28%) for the 5-9% group (P=0.17). Pairwise comparison showed significant difference between AP and the other groups (P=0.03). Spline function analyses using blasts as continuous variable and 3 knots showed no significant effect on non-relapse mortality but suggested increased risk of relapse for AP myelofibrosis (P=0.04). Multivariable analysis. Adjusting for clinical (diagnosis, leukocyte and platelet counts, age, constitutional symptoms) and molecular-genetic (driver mutation genotype, high-risk mutations), Cox model on survival (with the 0% group as reference) showed comparable risk of death across blast groups with hazard ratios of 1.06 (0.70-1.62) for the 1-4%, 1.11 (0.56-2.32) for the 5-9%, and 0.95 (0.49-1.86) for the AP group. Independent factors for worse outcome were age, platelet and leukocyte counts, and CALR/MPL-unmutated genotype. Conclusion Reduced intensity allogeneic stem cell transplantation for AP myelofibrosis was associated with excellent and similar survival and non-relapse mortality in comparison with other blast groups and after adjustment for other risk factors, offering long-term survival (>10 years) for more than half of patients at AP. Relapse incidence appeared to be increased for AP myelofibrosis. Disclosures Heuser: Karyopharm: Research Funding; Tolremo: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; BergenBio: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer Pharma AG: Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Thol: Pfizer: Honoraria; Abbvie: Honoraria; Astellas: Honoraria; BMS/Celgene: Honoraria, Research Funding; Jazz: Honoraria; Novartis: Honoraria. Scott: Bristol Myers Squibb: Consultancy, Honoraria, Research Funding. Kroeger: Neovii: Honoraria, Research Funding; Sanofi: Honoraria; Jazz: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Gilead/Kite: Honoraria; AOP Pharma: Honoraria; Novartis: Honoraria.

scholarly journals Characteristics of DNMT3A-R882 Mutation in AML

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5263-5263
Author(s):  
Olga Blau ◽  
Franziska Behrenbeck ◽  
Mirgul Bayanova ◽  
Igor-Wolfgang Blau ◽  
Lars Bullinger
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Standard Therapy ◽  
Research Funding ◽  
Advisory Committees ◽  
Mutation Burden

Abstract Introduction Genetic mutations play an important role in the development and progression of acute myeloid leukemia (AML). One of the common aberration in AML is mutation in the epigenetic modifying gene, DNA methyltransferase 3α (DNMT3A). Despite the active investigations, the exact impact of mutation on the development of AML is not completely known. The occurrence of mutation in pre-leukemic cells explains a particular attention to DNMT3A. The most common mutation is located in codon R882 (DNMT3AR882mut). The objective of this study is to compare clinical and prognostic characteristics of AML patients in relation to presence of DNMT3AR882mut. The quantification of the mutation burden in follow up samples was performed both after standard therapy and after allogeneic stem cell transplantation (alloSCT). In addition, it was investigated whether the quantification of the mutational burden of DNMT3AR882mut is significant to the progression of disease. Methods Samples of 580 AML were retrospective analyzed using HRM-PCR, capillare electrophorese, and Sanger Sequencing. The median observation period was 495 days. Of 580, 69 have DNMT3AR882mut. Mutation burden was evaluated in follow-up samples by quantitative PCR. The statistical methods were selected according to sample distribution and evaluated with SPSS (significance level p <0.05). Results DNMT3A R882mut were associated with a higher level of leukocytes and blasts at diagnosis, with M4-M5 variant of AML, and with normal karyotype. It was found that NPM1 and FLT3-ITD are more frequent co-mutations that have a significant effect on the prognosis of disease. Analysis of mutation burden of DNMT3AR882mut at diagnosis showed a large spread (0.02 - 66.9 %). At the time of diagnosis, DNMT3AR882mut transcript levels did not correlate with clinical and prognostic characteristics. The mutation burden decreased after therapy, but was always visible in CR after standard therapy. In CR after allogeneic stem cell transplantation (alloSCT) with complete donor chimerism mutation was not detected. In relapse of AML, an increasing of the mutation burden were found in all patients, both after therapy, and after alloSCT. In relapse samples, the same mutant clone was found. Conclusion The DNMT3A mutation is a common genetic aberration in AML patients, which is associated with specific clinical and prognostic data. The presence of co-mutations, especially NPM1 and FLT3-ITD, has a significant effect on the prognosis of patients. Quantitative detection of DNMT3AR882mut at different time points of disease revealed the persistence of mutated clone after standard therapy and disappearance of DNMT3AR882mut after alloSCT. It is suggest that alloSCT is the optimal treatment option for the eradication of DNMT3AR882mut in AML patients. Disclosures Bullinger: Sanofi: Research Funding, Speakers Bureau; Janssen: Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Pfizer: Speakers Bureau; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Bayer Oncology: Research Funding.

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 The Burden of Survivorship on Hematological Patients—Long-Term Analysis of Toxicities after Total Body Irradiation and Allogeneic Stem Cell Transplantation

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5640
Author(s):  
Michael Oertel ◽  
Jonas Martel ◽  
Jan-Henrik Mikesch ◽  
Sergiu Scobioala ◽  
Christian Reicherts ◽  
...  
Keyword(s):  
Stem Cell ◽  
Side Effects ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Total Body Irradiation ◽  
Whole Body ◽  
Total Body

Total body irradiation is an effective conditioning modality before autologous or allogeneic stem cell transplantation. With the whole body being the radiation target volume, a diverse spectrum of toxicities has been reported. This fact prompted us to investigate the long-term sequelae of this treatment concept in a large patient cohort. Overall, 322 patients with acute leukemia or myelodysplastic syndrome with a minimum follow-up of one year were included (the median follow-up in this study was 68 months). Pulmonary, cardiac, ocular, neurological and renal toxicities were observed in 23.9%, 14.0%, 23.6%, 23.9% and 20.2% of all patients, respectively. The majority of these side effects were grades 1 and 2 (64.9–89.2% of all toxicities in the respective categories). The use of 12 Gray total body irradiation resulted in a significant increase in ocular toxicities (p = 0.013) and severe mucositis (p < 0.001). Renal toxicities were influenced by the age at transplantation (relative risk: 1.06, p < 0.001) and disease entity. In summary, total body irradiation triggers a multifaceted, but manageable, toxicity profile. Except for ocular toxicities and mucositis, a 12 Gray regimen did not lead to an increase in long-term side effects.

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 Daratumumab (DARA) Maintenance Therapy Improves Depth of Response and Results in Durable Progression-Free Survival (PFS) Following Dara Plus Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) Induction Therapy in Multiple Myeloma (MM): Update of the Lyra Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 863-863 ◽  
Author(s):  
Robert M. Rifkin ◽  
Jason M. Melear ◽  
Edward Faber ◽  
William I. Bensinger ◽  
John M Burke ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Safety Profile ◽  
Employment Equity ◽  
Advisory Committees ◽  
Depth Of Response ◽  
Equity Ownership ◽  
Grade 3

Background: DARA, a human IgGκ monoclonal antibody targeting CD38, is approved in combination with bortezomib, melphalan, and prednisone (VMP) and bortezomib and dexamethasone (Vd) for newly diagnosed MM (NDMM) and relapsed MM (RMM), respectively. CyBorD is a commonly used immunomodulatory drug-sparing regimen for MM. In the LYRA (NCT02951819) study, DARA plus CyBorD (DARA-CyBorD) demonstrated efficacy and a tolerable safety profile at the end of induction. Here, we present updated findings examining the effect of monthly DARA maintenance on the efficacy and safety of DARA-CyBorD in NDMM and RMM. Methods: LYRA is an ongoing, single-arm, open-label, phase 2 study conducted at US community oncology centers. Patients (pts) were aged ≥18 years with documented MM per IMWG criteria, an ECOG performance score (PS) of 0-2, and ≤1 prior line of therapy. Pts received 4-8 induction cycles of DARA-CyBorD (cyclophosphamide 300 mg/m2 PO on Days 1, 8, 15, and 22; bortezomib 1.5 mg/m2 SC on Days 1, 8, and 15; and dexamethasone 40 mg PO or IV weekly [qw]) every 28 days. DARA was given at 8 mg/kg IV on Days 1 and 2 of C1, 16 mg/kg qw from C1D8 through C2, 16 mg/kg q2w for C3-6, and 16 mg/kg q4w for C7-8. After induction, eligible pts could undergo autologous stem cell transplantation (ASCT). All pts received up to 12 maintenance cycles with DARA 16 mg/kg IV q4w. Results: A total of 101 (87 NDMM, 14 RMM) pts were enrolled; 100 (86 NDMM, 14 RMM) pts received ≥1 treatment dose. Median age was 63 years; most pts were white (81%), male (64%), had ECOG PS 0-1 (94%) and had IgG (57%) MM; 36% of pts had high cytogenetic risk, defined as a del(17p), t(4:14) or t(14;16) abnormality. NDMM and RMM pts received a median of 6 and 8 cycles, respectively, of induction therapy. Thirty-nine NDMM pts and 1 RMM pt underwent ASCT. Fifty percent of pts received plerixafor; median stem cell yield for NDMM pts was 6.2 x 106 (range 2-15 x 106) CD34+ cells/kg. A total of 85 (75 NDMM, 10 RMM) pts received ≥1 dose of maintenance treatment; 63 (56 NDMM, 7 RMM) pts have received all 12 maintenance cycles. In NDMM pts, ORR was 87%, with 64% ≥VGPR and 12% ≥CR, by the end of induction. By the end of maintenance, ORR, ≥VGPR and ≥CR rates were 97%, 82% and 51% in NDMM pts who underwent ASCT and 83%, 70% and 30% in NDMM pts who did not receive ASCT. In RMM pts, ORR, ≥VGPR and ≥CR rates were 79%, 71% and 29% by the end of induction and 86%, 71% and 64% by the end of maintenance. At a median follow up of 24.8 mo in NDMM pts and 26.6 mo in RMM pts, median duration of response was not reached (NR). Median PFS (Figure) was NR in NDMM pts, regardless of transplant status, and was 21.7 mo in RMM pts; median OS was NR in NDMM pts and was 30.1 mo in RMM pts. In NDMM pts the 24-mo PFS rate was 89% in pts who underwent ASCT and 72% in pts who did not receive ASCT. The 24-mo OS rate was 90% for NDMM pts. In RMM pts, the 24-mo PFS and OS rates were 48% and 64%, respectively. All treated pts had ≥1 TEAE. Common TEAEs (≥25%) included fatigue, nausea, cough, diarrhea, upper respiratory tract infection, back pain, vomiting, insomnia, dyspnea, constipation, and headache. Grade 3/4 TEAEs were reported in 62% of pts; the most common (≥10%) was neutropenia (14%). Serious TEAEs occurred in 33% of pts; the most common (&gt;2%) were pneumonia, atrial fibrillation and pulmonary embolism. TEAEs led to permanent treatment discontinuation in 7% of pts, with 2% related to treatment. TEAEs resulted in death in 2 pts (nephrotic syndrome, sudden death); both unrelated to treatment. Infusion reactions (IRs) occurred in 56% of pts including grades 1-2 in 52% of pts, grade 3 in 3% of pts and grade 4 in 1% of pts. Most common (&gt;5%) IRs were chills, cough, dyspnea, nausea, pruritus, flushing and nasal congestion. Conclusion: Maintenance with DARA monotherapy for 12 mo increased the &gt;CR rate in NDMM and RMM pts, consistent with observations in prior studies that longer DARA treatment improves depth of response. Importantly, the increase in ≥CR rate was associated with durable PFS and OS. The 24-mo PFS rates in NDMM and RMM pts compare favorably with results for DARA-VMP and DARA-Vd in NDMM and RRMM, respectively. Safety profile was consistent with previous reports of DARA, with no new safety concerns observed with longer follow-up. These data indicate that DARA-CyBorD is a safe, effective MM treatment and that DARA maintenance increases depth of response and achieves durable remissions. Disclosures Rifkin: Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Melear:Texas Oncology: Employment; DARA: Speakers Bureau. Faber:Cardinal Health: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Bensinger:Amgen, Celgene: Other: Personal Fees, Research Funding, Speakers Bureau; Takeda, Janssen: Speakers Bureau; Sanofi, Seattle Genetics, Merck, Karyopharm: Other: Grant. Burke:Gilead: Consultancy; Celgene: Consultancy; Roche/Genentech: Consultancy. Narang:Celgene: Speakers Bureau. Stevens:Astellas: Consultancy. Gunawardena:Janssen: Employment, Equity Ownership. Lutska:Janssen: Employment. Qi:Janssen: Employment. Ukropec:Janssen: Employment, Equity Ownership. Qi:Janssen: Employment. Lin:Janssen: Employment, Equity Ownership. Yimer:Amgen: Consultancy; Clovis Oncology: Equity Ownership; Puma Biotechnology: Equity Ownership; Celgene: Honoraria; Seattle Genetics: Honoraria; Janssen: Speakers Bureau; AstraZeneca: Speakers Bureau.

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