scholarly journals Feasibility and efficacy of salvage allogeneic stem cell transplantation in AML patients relapsing after autologous stem cell transplantation

2021 ◽  
Author(s):  
Evgenii Shumilov ◽  
Inna Shakhanova ◽  
Johanna Flach ◽  
Nicole Schmidt ◽  
Susanne Buerki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
Palliative Therapy ◽  
High Dose ◽  
Front Line ◽  
Curative Intent ◽  
Allogeneic Hct ◽  
Autologous Hct

AbstractAutologous hematopoietic cell transplantation (HCT) is suitable for consolidation of favorable-/intermediate-risk AML patients in CR1. However, ~50% of AML patients relapse after autologous HCT, and efficacy of subsequent salvage strategies including allogeneic HCT remains unclear. We studied 123 consecutive patients with newly diagnosed AML undergoing high-dose chemotherapy (HDCT)/autologous HCT in CR1. In relapsing patients afterwards, we analyzed salvage treatments and outcomes focusing particularly on salvage allogeneic HCT. Of 123 patients, 64 (52%) relapsed after autologous HCT. Subsequently, 13 (21%) received palliative therapy, whereas 51 (79%) proceeded to salvage therapy with a curative intent. Of the 47 patients with a curative intent and who did not proceed directly to allogeneic HCT, 23 (49%) achieved CR2 or had ongoing hematologic CR1 despite molecular relapse. Finally, 30 patients (47%) received allogeneic HCT with estimated 3-year leukemia-free and overall survival rates of 33% and 43%. Hematologic remission at allogeneic HCT and lack of acute GvHD had a positive impact on OS and LFS (p < 0.05). Our study suggests that almost 80% of AML patients can undergo salvage therapy following relapse after front-line HDCT/autologous HCT. Allogeneic HCT can provide cure in one third of patients relapsing after front-line HDCT/autologous HCT.

scholarly journals Stem cell transplantation after salvage therapy with high-dose cytarabine and amsacrine in adults with high-risk leukaemia

2003 ◽  
Vol 32 (3) ◽  
pp. 273-278 ◽  
Author(s):  
S Tauro ◽  
P Shankaranarayana ◽  
I C Nitu-Whalley ◽  
N Duncan ◽  
G Begum ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
High Dose ◽  
High Dose Cytarabine

Front-Line Consolidation with Autologous Stem Cell Transplantation in Patients with Nodal Aggressive Peripheral T-Cell Lymphoma (PTCL). A Prospective Study of the GEL-TAMO.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2463-2463
Author(s):  
Jose Rodriguez ◽  
Eulogio Conde ◽  
Antonio Gutierrez ◽  
Reyes Arranz ◽  
Angel Leon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Salvage Therapy ◽  
Front Line ◽  
Free Survival ◽  
Line Therapy ◽  
Gallium Scan

Abstract Background: Nodal aggressive PTCL have a poor prognosis with conventional chemotherapy regimens for aggressive non-Hodgkin lymphomas. Therefore innovative approaches are needed. Among them, strategies including consolidation with high-dose chemotherapy and autologous stem cell transplantation in front line therapy may improve the outcome of these diseases. Aim: To report the experience of a national cooperative group in 26 patients with aggressive nodal PTCL who underwent treatment including ASCT as consolidation of front line therapy. Patients and Methods: Twenty-six patients Gallium scan positive with nodal PTCL entered into the study: 11 cases of PTCL-unspecified (42%), 8 ALCL (31%) and 7 AIL (27%). Patients received three courses of MegaCHOP and subsequently were evaluated by CT scan and Gallium scan. Those patients Gallium scan negative received another course of MegaCHOP and then the transplant. Those patients Gallium scan positive after 3 courses of MegaCHOP received 2 courses of the IFE regimen (Ifosfamide 3.3g/m2 days 1–3 and Etoposide 300 mg/m2 days 1–3) and if at least achieved a partial response received the transplant otherwise they are out of the study. Median age was 44 years, 96% of the patients presented Ann Arbor stage III or IV; 54% presented B symptoms; 31% bone marrow involvement and 72% of the patients presented 2–3 factors of the a-IPI. Results: Thirteen patients (50%) achieved a CR after 3 courses of MegaCHOP and 12 patients received IFE as salvage therapy. Twenty patients out of the 26 initial patients were able to proceed to the transplant. After the transplant 85% of patients achieved a CR. The 6 patients who did not received the transplant was due to progression of the disease in 4 cases, lethal toxicity in one case and refusal in another case. With a median follow up of 35 months for alive patients, the overall survival (OS) and progression-free survival (PFS) at 3 years were 73% and 53%, respectively. OS, PFS and disease-free survival for the 20 patients who underwent the ASCT consolidation was 84%, 53% and 63%, respectively. Conclusion: Early salvage therapy for patients not in CR after 3 courses of chemotherapy and ASCT consolidation for chemosensitive patients may improve the outcome of patients with nodal aggressive PTCL. Larger series and longer follow up are needed to confirm this promising approach.

Minimum tolerable interval of 90yttrium ibritumomab-tiuxetan to autologous stem cell transplantation after high-dose chemotherapy with carmustin, etoposide, cytarabine, and melphalan for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6543-6543 ◽  
Author(s):  
Justin Hasenkamp ◽  
Georg Hess ◽  
Bernd Hertenstein ◽  
Peter Dreger ◽  
Lutz Uharek ◽  
...  
Keyword(s):  
Body Weight ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Salvage Therapy ◽  
Maximum Tolerated Dose ◽  
High Dose ◽  
Time Interval ◽  
Ibritumomab Tiuxetan

6543 Background: High-dose therapy and autologous stem cell transplantation (ASCT) in patients (pts) with aggressive B-NHL failing from immunochemotherapy including rituximab show poor outcome with 3y PFS of 39% (Gisselbrecht et al. JCO 2010). Combining BEAM with 90yttrium ibritumomab tiuxetan is a promising option to enhance the efficacy of the high-dose regimen. Methods: Pts without disease progression during salvage therapy of relapsed or refractory CD20+ aggressive B-NHL were included in this prospective, multicenter, phase I/II trial. Primary endpoint was the maximum tolerated dose of 90Yttrium ibritumomab tiuxetan given as close as possible to ASCT defined as <2 pts with dose limiting toxicity in a 6+6 pts cohort. First, we reduced the time interval of 90yttrium ibritumomab tiuxetan (0.4 mCi/kg body weight) to ASCT from 14 to 12 and then 10 days. Subsequently it was planned to increase the 90yttrium ibritumomab tiuxetan dose. Results: From 2006 to 2009 26 pts, median age 58y (34-66) were enrolled. Histology included 14 DLBCL, 6 FL III°, 5 transformed FL and 1 aggressive B-NHL without further subtyping. 11/26 pts had relapse/progression within 1y after diagnosis. Secondary IPI was >1 in 14 pts. Response to salvage therapy was CR in 6/26 pts and PR in 12/26 pts. 20/26 pts achieved CR after ASCT. Engraftment showed no significant differences in pts of different cohorts with median recovery of leukocytes (>1/nl) and platelets (>25/nl) at d +10 and +13. Two early deaths (d +7, +18) occurred due to infections. 90Yttrium ibritumomab tiuxetan (0.4 mCi/kg body weight) at d -10 of ASCT was determined as minimum tolerated interval of radioimmunotherapy to ASCT after BEAM. Median follow-up of the survivors is 3.3 y. 3y PFS and OS is 67% (95% CI, 49%-85%) and 75% (95% CI, 58%-92%), respectively. Main cause of death was relapse/progression with 27% (95% CI, 6%-38%) at 3y. Conclusions: Z-BEAM followed by ASCT was safe and feasible and results in a high response rate with durable remissions in rituximab pretreated patients with aggressive B-NHL. Extended studies at the maximum tolerated dose and confirmation of superiority compared to conventional ASCT are warranted.

A Single Institution Long-Term Experience Using Autologous Stem Cell Transplantation for the Management of Hodgkin’s Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5233-5233
Author(s):  
Barry S. Skikne ◽  
Narotham Thudi ◽  
Delva Deauna-Limayo ◽  
Siddhartha Ganguly ◽  
David Bodensteiner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Free Survival ◽  
Primary Induction ◽  
Induction Failure

Abstract Patients with stage III – IV Hodgkin’s lymphoma (HL), and those with bulky stage I/II disease have a disease relapse rate of 30–40% after primary treatment. High dose chemotherapy with stem cell transplantation is a treatment option after relapse or in those with primary induction failure. In the present study, we retrospectively examined long term outcomes in 45 relapsed/primary induction failure HL patients undergoing autologous peripheral stem cell (25 patients), bone marrow (17 patients) or combination (3 patients) transplantation between 1985 and December 2003. The median age was 32 yrs(16–64), 38 had Nodular Sclerosing HL, 17 patients had stage I/II, 13 stage III and 15 stage IV disease, and 33 had B symptoms at diagnosis. Twenty patients were previously treated with 1–2 prior regimens, while 25 had ≥3 treatment regimens. Sixteen patients had sensitive disease to salvage therapy given prior to transplantation, 27 had resistance to salvage therapy while 2 did not undergo salvage therapy prior to transplantation. Five patients had primary resistant disease, 33 had evidence of relapsed disease and 7 patients were in CR at the time of transplantation. CBV was used in 30 patients, BEAM in 9 patients and 5 patients received CY/TBI based regimens. Six patients (13%) had early mortality (< 100 days) directly attributable to the procedure. Four of these deaths were cardiac related and two were due to infection. The overall response was 93% with CR achieved in 28 (62%) and incomplete response in 14 (31%). The median overall survival (OS) was 5.5 yrs, the median disease free survival (DFS) was 1 yr with DFS at 5 yrs of 26%. For patients achieving a CR after transplantation, 67% remain alive at a median of 7 yrs from transplant, however, the median progression free survival in these patients was 3.7yrs. For 15 patients not achieving CR after transplantation, 3(20%) have survived, the median time to death in this group was 20 months. Seventeen patients are alive, 2 are lost to follow-up and 21 patients have died. Fourteen patients died from disease progression (31%), 2 (4%) died from MDS/AML occurring after 32 and 66 mnths, 2 died of late occurring infections, 2 related to respiratory failure and a further patient from late cardiac failure. OS and DFS did not differ between peripheral stem cell vs bone marrow transplantation, those with B symptoms at diagnosis, sex differences, age <20yrs vs >20yrs, high dose therapy regimens but a difference in OS (p=0.04) and DFS (p=0.03) was seen in patients transplanted in CR vs active disease at transplantation. Patients whose disease displayed sensitivity to salvage therapy immediately prior to transplant did show a trend towards improved OS and DFS, but this was not statistrically significant. High dose chemotherapy and autologous stem cell transplantation can be expected to lead to long term DFS in approximately 25–35% of patients. Cardiac mortality (11%) appears to be a higher than expected complication in this patient group.

Identical Outcome Following Autologous or Allogeneic Genoidentical Hematopoietic Stem Cell Transplantation in First Complete Remission for Good Risk Acute Myelocytic Leukemia Carrying INV 16 or t(8;21): A Retrospective Comparison from the Acute Leukemia Working Party (ALWP) of the European Cooperative Group for Blood and Marrow Transplantation (EBMT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 605-605
Author(s):  
Norbert C. Gorin ◽  
Myriam Labopin ◽  
Francesco Frassoni ◽  
Emmanuelle Polge ◽  
Vanderson Rocha ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Chromosome Abnormality ◽  
Autologous Transplantation ◽  
High Dose ◽  
Front Line ◽  
Additional Chromosome ◽  
Good Risk

Abstract Patients with acute myelocytic leukaemia (AML) with core binding factor mutations (CBF), bearing abnormalities of chromosome 16 or t(8;21) are classified as good risk with chemotherapy regimens including high dose cytosine arabinoside and are not subjected to hemopoietic stem cell transplantation (HSC) front line. However there are limited data from old studies indicating good outcome following HSC, autografting in particular, and there has been recently some concern about higher than expected relapse incidence following conventional chemotherapy in this patient population. From January 1990 to December 2004, a total of 325 adult patients were reported to the EBMT Acute Leukemia registry as receiving a transplant in first remission (CR1). Of these, 159 had an inversion 16, including 124 with no additional chromosome abnormality and 35 with other abnormalities. 166 had a t(8;21) translocation, as the only chromosome abnormality in 106 and associated to other abnormalities in 60. 64 patients with inv 16 and 81 patients with t(8;21) received a geno-identical allograft. 95 patients with inv 16 and 85 patients with t(8;21) translocation received an autograft. In patients with inv 16, following allogeneic and autologous transplantation respectively, the LFS were 59 ± 7% and 66 ± 5% (p=0.5), the RI 27 ± 6% and 32 ± 4% (p=0.45) and the TRM 14 ± 4% and 2 ± 2% (p=0.003). The LFS was significantly higher after January 2001. Female patients had a significantly lower incidence of relapse and a higher LFS. The existence of additional chromosome abnormalities not only did not worsen the prognosis but was associated with less relapses (12±5% vs 34 ± 4%, p= 0.01), and a better LFS (78 ± 7% vs 59 ± 5%, p=0.04). In patients with t(8;21), following allogeneic and autologous transplantation respectively, the LFS were 60 ± 5% and 66 ± 5% (p=0.69), the RI 15 ± 2% and 28 ± 3% (p=0.03) and the TRM 24 ± 3% and 6 ± 1% (p=0.003). Younger age and a lower white cell count at diagnosis were associated with a lower TRM and a better LFS.There was no difference in outcome between female and male patients. Following autologous transplantation as compared to allogeneic, the TRM was significantly lower and the relapse incidence significantly higher. For all adult CBF AML, the LFS did not differ between autologous and allogeneic transplants. Although the reasons why these patients were transplanted are unclear, considering the low TRM of autologous stem cell transplantation and the possibility to monitor in vivo purging by molecular biology, the data support the inclusion of ASCT in the front line treatment of CBF AML and suggest that a randomized prospective trial comparing high dose ARA-C and ASCT would be of interest.

scholarly journals THE ROLE OF AUTOLOGOUS AND ALLOGENEIC STEM CELL TRANSPLANTATION IN FOLLICULAR LYMPHOMA IN THE NEW DRUGS ERA.

2016 ◽  
Vol 8 ◽  
pp. e2016045 ◽  
Author(s):  
Francesco Maura ◽  
Lucia Farina ◽  
Paolo Corradini
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Salvage Therapy ◽  
Remission Rate ◽  
High Dose Chemotherapy ◽  
New Drugs ◽  
High Dose

Follicular lymphoma (FL) is the second most common histotype of non-Hodgkin’s lymphoma and it is generally characterized by a heterogeneous clinical course. Despite recent therapeutic and diagnostic improvements, a significant fraction of FL patients still relapsed. In younger and/or fit FL relapsed patients bone marrow transplant (BMT) has represented the main salvage therapy for many years. Thanks to the ability of high dose chemotherapy to overcome the lymphoma resistance and refractoriness, autologous stem cell transplantation (ASCT) is able to achieve a high complete remission rate (CR) and favourable outcome in terms of progression free survival (PFS) and overall survival (OS). Allogeneic stem cell transplantation (alloSCT) combines the high dose chemotherapy effect together with the immune reaction of the donor immune system against lymphoma, the so called ‘graft versus lymphoma’ (GVL) effect. Considering the generally higher transplant related mortality (TRM), alloSCT is mostly indicated for FL relapsed after ASCT. During the last years there has been a great spread of novel effective and feasible drugs Although these and future novel drugs will probably change our current approach to FL, the OS post-BMT (ASCT and alloSCT) has never been reproduced by any novel combination. In this scenario, it is important to correctly evaluate the disease status, the relapse risk and the comorbidity profile of the relapsed FL patients in order to provide the best salvage therapy and eventually transplant consolidation.

Minimum Tolerable Interval of Radioimmunotherapy and Autologous Stem Cell Transplantation after High-Dose Chemotherapy for Relapsed or Refractory Aggressive B Cell Non-Hodgkin-Lymphoma Provides Excellent Disease Control

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3986-3986
Author(s):  
Justin Hasenkamp ◽  
Georg Hess ◽  
Bernd Hertenstein ◽  
Mathias Witzens-Harig ◽  
Lutz Uharek ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Control ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Salvage Therapy ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Ibritumomab Tiuxetan ◽  
Non Hodgkin Lymphoma

Abstract Background: Patients with aggressive B cell Non-Hodgkin-Lymphoma failing from immune-chemotherapy show disappointing results with standard salvage therapies and consolidation of high-dose chemotherapy with autologous stem cell transplantation. Especially in cases never in remission or with early relapse outcome is poor. Several groups started trials combining high-dose chemotherapy of carmustin, etoposide, cytarabine and melphalan (BEAM) with 90Yttrium ibritumomab tiuxetan to enhance the efficacy of the preparative regimen. In this trial we tested safety, feasibility and studied efficacy of reduced intervals of 90Yttrium ibritumomab tiuxetan to autologous stem cell transplantation after BEAM. Methods: Patients without disease progression during salvage therapy of relapsed or refractory CD20+ aggressive B-NHL were included in this prospective, multicenter, phase I/II trial. Primary endpoint was the minimum tolerable interval of 90Yttrium ibritumomab tiuxetan given as close as possible to ASCT defined as <2 patients with dose limiting toxicity in a 6+6 patient cohort. We reduced the time interval of standard dose 90Yttrium ibritumomab tiuxetan (0.4 mCi/kg body weight) to ASCT after BEAM from 14 to 12 and finally 10 days to foster the disease control by more concomitant radioimmunotherapy and high-dose chemotherapy. Results: From 2006 to 2009 42 patients were screened for inclusion. Reasons for screening failure were progressive disease during salvage therapy (n=8), death (n=2), not aggressive B-NHL (n=2), impaired organ function (n=2), and other (n=2). Median age of the 26 patients enrolled was 58 years (34-66). 12 patients were allocated to cohort 1 (interval 14 days), 6 patients to cohort 2 (interval 12 days) and 8 patients to cohort 3 (interval 10 days). Histology included 14 DLBCL, 6 FL III°, 5 transformed FL and 1 aggressive B-NHL without further subtyping. 11 from 26 patients had primary refractory disease or early relapse within 12 months after diagnosis. Secondary IPI was >1 in 14 patients. Response to salvage therapy was CR in 6/26 patients and PR in 12/26 patients. 20/26 patients achieved CR after study treatment. Two early deaths (d +7, +18) occurred due to infections. All patients receiving stem cells engrafted with median recovery of leukocytes and platelets at d+10 and +13, respectively. We observed no correlation of toxicities and the study cohorts with the different intervals. At median follow-up of the survivors of 3.5 years the overall survival is 76%, the progression free survival is 67% and time to progression 26%. Lymphoma was the main cause of death. Stratified to time intervals of 90Yttrium ibritumomab tiuxetan and autologous stem cell transplantation revealed time to progression of 50% with 90Yttrium ibritumomab tiuxetan at d-14, 16% at d-12 and 0% at d-10. Conclusions: 90Yttrium ibritumomab tiuxetan and BEAM followed by autologous stem cell transplantation was safe and feasible. The minimum tolerable interval of 90Yttrium ibritumomab tiuxetan and autologous stem cell transplantation is 10 days. With shorter intervals of radioimmunotherapy and high-dose chemotherapy and therefore more concomitant therapy, we did not observed excessive toxicity, but enhanced disease control of refractory or relapsed aggressive B-NHL. Our results compare favorable to standard BEAM or allogeneic stem cell transplantation. A formal comparison in a phase III trial is warranted. Disclosures Off Label Use: 90Yttrium ibritumomab tiuxetan (Zevalin(R)), radioimmunotherapy of CD20+ lymphoma.

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