Reduced Intensity Stem Cell Transplant (RIST) as Salvage Treatment for Relapse Following Myeloablative Allogeneic Transplantation in Adult Acute Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5374-5374
Author(s):  
R. Alejandro Sica ◽  
Joseph M. Tuscano ◽  
Lisa Y. Law ◽  
Carol M. Richman
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Cell Transplant ◽  
Peripheral Blood Stem Cells ◽  
Dismal Prognosis ◽  
Acute Myeloid

Abstract Relapse of acute myeloid leukemia (AML) following myeloablative allogeneic stem cell transplantation portends a dismal prognosis. Therapy aimed at enhancing graft-versus-leukemia (GVL) effect, e.g., by donor leukocyte infusion, has limited success in AML, and a second ablative transplant is associated with prohibitive mortality in adults. From April 2001 to March 2006, nine patients, ranging in age from 21 to 57, with high risk myeloid malignancy (7 AML and 2 advanced myelodysplasia) and overt bone marrow relapse less than one year after ablative busulfan/cyclophosphamide conditioning have been treated with a cytoreductive regimen of fludarabine (30 mg/m2/day) and cytarabine (2g/m2/day) for 5 days (-7 through -3) and G-CSF administration (5 ug/kg daily starting day -8) with or without idarubicin (8 mg/m2 days -7, -5, and -3) (8 cases) or fludarabine 30 mg/m2 for 3 days and 200 cGy total body irradiation (1 case). G-CSF mobilized peripheral blood stem cells from their original HLA-matched donor (8 siblings, 1 unrelated) were infused. Graft versus host disease (GVHD) prophylaxis was mycophenolate mofetil for 30 days and cyclosporine with a rapid taper. The mean onset of relapse after the initial ablative transplant was day 172 (range 106–271). Fludarabine-based therapy was well tolerated with no treatment related mortality. Full donor chimerism was established by day 72 (range 26–113) in 6 patients (67%). Five patients died: 2 from relapse without GVHD at day +30 and +301 after RIST (one patient with complex and one with Ph+ cytogenetic abnormalities), 3 from relapse with evidence of GVHD. Four patients survive: one has relapsed at 91 days after RIST and is receiving alternate therapy, while three patients (30%) survive in complete remission at 100+, 635+ and 1795+ days after salvage RIST. In 5 cases (56%), the duration of complete remission after RIST was longer than after the initial ablative transplant. We conclude that fludarabine-based RIST is a safe and effective salvage therapy offering a chance for increased survival with low morbidity in patients relapsing after ablative transplant. In addition, RIST therapy has resulted in long-term disease free survival in over 20% of cases in this study.

Successful Salvage Treatment With Clofarabine and Cytarabine In Relapsed/Refractory Acute Myeloid Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5039-5039
Author(s):  
Alessandra Malato ◽  
Francesco Acquaviva ◽  
Alessandra Santoro ◽  
Rosaria Felice ◽  
Silvana Magrin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Stem Cell Transplant ◽  
Remission Rate ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Refractory Acute Myeloid Leukemia ◽  
Acute Myeloid

Abstract Objectives Relapsed/refractory AML patients  have a poor prognosis; allogeneic hematopoietic stem cell transplantation (HSCT) is the only chance in this setting to achieve long-term disease-free survival (1). It was previously established the activity of clofarabine plus cytarabine in AML relapse (clofarabine dosed once daily for 5 days with 40 mg/m2  followed 4 hours later by ara-C at 1 g/m2 per day)(2).However, modifications of this combination in AML therapy of relapsed/refractory patients warrant further evaluation. Therefore, our goal was to determine the efficacy and safety of clofarabine at lower dosage followed by  cytarabine (Ara-C) in adult patients with relapsed or refractory acute myeloid leukemia (AML) and to evaluate the capacity of this regimen as a bridge for HSCT. Methods Patients aged 18-65 years with refractory/relapsed AML were treated at the dose of clofarabine 30 mg/mq on days 1-5 and cytarabine 1000 mg/mq gg on days 1-5. We evaluated the complete remission rate (CRR), duration of remission (DOR) and overall survival (OS). Minimal residual disease (MRD) by molecular targeting was considered in all patients. Results Twenty-five (25) patients aged 29-64 years (median 47), who were fit for allogenetic HCT,  received one cycle of 30 minutes infusion of  clofarabine 30 mg/mq, followed 4 hours later by 3 hours infusion of  intermediate dose cytarabine 1000 mg/mq  days 1-5. Only in the first three patients this schedule was followed by gentuzumab. Nine (36%) patients had refractory disease (seven after one induction regimen, one after two previous regimes, one after a prior hematopoietic stem cell transplant (HSCT);  16 (64%) patients  were in their first (12 patients) or second relapse (4 patients); among the 12 patients in first relapse, 5 were from an allogeneic stem cell transplant.  Fourteen patients (56%)  achieved a complete remission (CR), seven (28%) was refractory and 4 (16%) died of treatment related mortality. Eleven (44%) patients  underwent (9 in CR) to allogeneic transplants or DLI infusion (3 patients refractory, and 8 patients relapsed), only one  patient underwent to autologous transplant. One patient, who was relapsed after prior HSCT, obtained a CR but he developed acute  graft vs host disease after therapy  and died in molecular CR*.  Among all patients underwent HSCT after Clofa/Ara-c salvage, six patients (50%) are still alive and in complete remission, six patients (50%) died because of  HSCT complications or AML relapse. The complete remission rate (CRR) was  (56,00 %), the median  Overall Survival  was 5 months for all patients (range 1-38 M), 11 Months for those underwent to tranplantation and 1,5 Months for non transplanted group. Treatment was complicated by neutropenic fever (n=17), grade III-IV mucositis (n=2) , skin rush  (n=4) grade II- III, hepatic transaminase elevations (n=2).  Two (n=5) patient died before their disease status could be evaluated. Conclusions These preliminary results suggest that combination treatment with clofarabine 30 mg/mq and ARA-C 1000 mg/mq is effective in this particularly poor prognosis category of patients, resulting in an ORR very favorably,  representing a potential “bridge” toward bone marrow transplant procedures (among the 14 patients who achieved a CR, twelve (85%) proceeded to HSCT, and six are still alive). The safety profile is acceptable in this relapsed/refractory population, and our results are very similar to previous regimes using higher clofarabine dosages.  More studies with this combination in adults are warranted. References 1 Estey E. Treatment of relapsed and refractory acute myeloid leukemia. Leukemia. 2000;14:476-479. 2. Faderl S et al, “Results of a pase 1-2 study of clofarabine in combination with cytarabine (ara-C)”Blood 2005 Disclosures: No relevant conflicts of interest to declare.

The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission

Blood ◽  
2012 ◽  
Vol 119 (23) ◽  
pp. 5584-5590 ◽  
Author(s):  
Xiao-Jun Huang ◽  
Hong-Hu Zhu ◽  
Ying-Jun Chang ◽  
Lan-Ping Xu ◽  
Dai-Hong Liu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract We report the results of a prospective, patient self-selected study evaluating whether haploidentical related donor stem cell transplantation (HRD-HSCT) is superior to chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia (AML) in first complete remission (CR1). Among totally 419 newly diagnosed AML patients, 132 patients with intermediate- and high-risk cytogenetics achieved CR1 and received chemotherapy alone (n = 74) or HSCT (n = 58) as postremission treatment. The cumulative incidence of relapse at 4 years was 37.5% ± 4.5%. Overall survival (OS) and disease-free survival (DFS) at 4 years were 64.5% ± 5.1% and 55.6% ± 5.0%, respectively. The cumulative incident of relapse for the HRD-HSCT group was significantly lower than that for the chemotherapy-alone group (12.0% ± 4.6% vs 57.8% ± 6.2%, respectively; P < .0001). HRD-HSCT resulted in superior survival compared with chemotherapy alone (4-year DFS, 73.1% ± 7.1% vs 44.2% ± 6.2%, respectively; P < .0001; 4-year OS, 77.5% ± 7.1% vs 54.7% ± 6.3%, respectively; P = .001). Multivariate analysis revealed postremission treatment (HRD-HSCT vs chemotherapy) and high WBC counts at diagnosis as independent risk factors affecting relapse, DFS, and OS. Our results suggest that HRD-HSCT is superior to chemotherapy alone as postremission treatment for AML.

scholarly journals ERRATUM: A unique case of durable complete remission after salvage with azacitidine and DLI for high risk flt-3 positive acute myeloid leukemia, following relapse 18 months post allogeneic stem cell transplant

2020 ◽  
Vol 12 (2) ◽  
Author(s):  
Claire Horgan ◽  
Alexandros Kanellopoulos ◽  
Shankara Paneesha ◽  
Bhuvan Kishore ◽  
Richard Lovell ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Unique Case ◽  
Acute Myeloid

Due to an error, Dr. Nikolousis’s last name was mistakenly spelled in this article (published in 2019 in Hematology Reports DOI: 10.4081/hr.2019.7800). The correct author’s name appears above in italics.

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