Chemotherapy Versus Hypomethylating Agents for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome Following Allogeneic Stem Cell Transplant: A Retrospective Review

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3944-3944
Author(s):  
Ibraheem H Motabi ◽  
Jingxia Liu ◽  
Camille N. Abboud ◽  
Amanda F. Cashen ◽  
Keith E. Stockler-Goldstein ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myeloid Leukemia ◽  
Stem Cell Transplant ◽  
Response Rate ◽  
Cell Transplant ◽  
Intensive Chemotherapy ◽  
Hypomethylating Agents ◽  
Allogeneic Stem Cell Transplant ◽  
Chemotherapy Group ◽  
Acute Myeloid

Abstract Allogeneic stem cell transplant (allo-SCT) is a potentially curative option for high risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Disease relapse after transplant is the major cause of treatment failure and is associated with a poor outcome. Intensive chemotherapy followed by donor lymphocytes infusion (DLI) or a second SCT may result in a durable response in some patients, but is associated with increased toxicity. More recently, a less aggressive therapy with hypomethylating agents (HA) has been reported to have activity in treatment of post-SCT relapse. We compared the treatment outcomes of intensive chemotherapy with that of HA. The primary end points were overall response rate (ORR) and overall survival (OS). Secondary endpoints were complete remission (CR) rate and progression free survival (PFS). A total of 100 patients with AML in morphological evidence of relapse were included: 73 patients received chemotherapy and 27 patients received a HA. Fifty-six percent of patients in the chemotherapy group and 33% of patients in the HA group received at least one DLI after treatment. Treatment with chemotherapy resulted in a higher ORR (51% vs. 18.5%, p = 0.004) and a higher CR rate (40% vs. 7%, p= 0.002). The median OS (6 months vs. 4 months, p = 0.024) and PFS (8 months vs. 2.3 months, p = 0.053) were longer in chemotherapy group. The overall survival (OS) at one year was 32% in the chemotherapy group compared with 4% in the HA group (p = 0.024). Similar benefit of chemotherapy over HA was maintained in all treatment outcomes after controlling for the use of DLI. The use of chemotherapy followed by DLI may offer the greatest benefit ( ORR of 68%; 1-year OS of 44%; and median OS of 18 months). Conclusion: our results suggest that intensive chemotherapy may result in a better response rate and a better overall survival compared with hypomethylating therapy in patients with morphological relapse of AML after SCT. We propose prospective studies before the use of hypomethylating agents in this setting for medically fit patients. Disclosures Off Label Use: Rituximab is a genetically engineered monoclonal antibody that targets a specific protein, known as CD20 found on the surface of normal and malignant B-lymphocytes.Use of Rituximab treatment for other than FDA approved indications include a rare condition of acquired factor VIII inhibitors in individuals without inherited hemophilia as an autoimmune phenomenon that may lead to life-threatening bleeding. Due to the low incidence rate of acquired inhibitors, published data consists of only case reports, and reviews.. Vij:celgene: Honoraria, Research Funding.

Treatment with FLAG followed by second allogeneic stem cell transplant for relapsed acute myeloid leukemia and myelodysplastic syndrome.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18503-e18503
Author(s):  
Brian Pham ◽  
Rasmus Hoeg ◽  
Nisha Hariharan ◽  
Kathyryn Alvarez ◽  
Aaron Seth Rosenberg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Time To Relapse ◽  
Acute Myeloid

e18503 Background: There is no standard treatment for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) relapsing after allogeneic stem cell transplant (SCT). Options include combination chemotherapy, withdrawal of immunosuppression, donor lymphocyte infusion (DLI), and second SCT. Previous studies have used fludarabine, cytarabine, and granulocyte colony stimulating factor (FLAG) or second SCT separately for salvage therapy. Our institution uses FLAG followed by SCT from the same donor (FLAG/SCT) in this setting. We report a retrospective study of FLAG/SCT in MDS and AML patients relapsed after SCT. Methods: Patients who received FLAG/SCT for treatment of relapsed AML or MDS between 2009 and 2018 were identified using the bone marrow transplant database at University of California Davis. Their baseline characteristics and outcomes were determined using the electronic medical record. Descriptive statistics and Kaplan-Meier survival analysis were used to describe patients, rates of graft-versus-host disease (GvHD) and estimate survival times. Results: Nineteen patients received FLAG/SCT for AML (n=18) and MDS (n=1). Median time to relapse from first SCT was 145 days (range 41 to 960 days). Prior to FLAG/SCT, 17 patients had medullary relapse (median bone marrow blasts 27%; range 7-85%). Two patients had extramedullary relapse. Eighteen (94.7%) patients achieved complete remission (CR) after FLAG/SCT. Median follow-up time was 354 days from the first day of FLAG/SCT (range 7 to 2144 days). Six patients (31.6%) relapsed with median time to relapse of 334 days (range 78 to 679 days) after treatment. Overall survival at 2 years was 52.5%. Causes of death were relapsed AML (n=4; 21.1%), infection (n=4; 21.1%) complications of GvHD (n=3,15.8 %), and brain herniation (n=1, 5.3%). Acute GvHD grade I-IV and new onset chronic GvHD occurred in thirteen (68.4%) and eight patients (42.1%), respectively. Conclusions: FLAG/SCT for AML and MDS relapsing after SCT resulted in a high remission rate. The overall survival of over two years suggests that the second SCT augmented the graft versus leukemia effect. The GvHD rate increased after second SCT, but the rate and severity were manageable. FLAG/ SCT is a reasonable option for relapsed AML and MDS after SCT.

scholarly journals CD34+CD38−CD123+ Leukemic Stem Cell Frequency Predicts Outcome in Older Acute Myeloid Leukemia Patients Treated by Intensive Chemotherapy but Not Hypomethylating Agents

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1174 ◽  
Author(s):  
François Vergez ◽  
Marie-Laure Nicolau-Travers ◽  
Sarah Bertoli ◽  
Jean-Baptiste Rieu ◽  
Suzanne Tavitian ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Prognostic Impact ◽  
Intensive Chemotherapy ◽  
Leukemic Stem Cell ◽  
Hypomethylating Agents ◽  
Chemotherapy Group ◽  
Acute Myeloid

The prognostic impact of immunophenotypic CD34+CD38−CD123+ leukemic stem cell (iLSC) frequency at diagnosis has been demonstrated in younger patients treated by intensive chemotherapy, however, this is less clear in older patients. Furthermore, the impact of iLSC in patients treated by hypomethylating agents is unknown. In this single-center study, we prospectively assessed the CD34+CD38−CD123+ iLSC frequency at diagnosis in acute myeloid leukemia (AML) patients aged 60 years or older. In a cohort of 444 patients, the median percentage of iLSC at diagnosis was 4.3%. Significant differences were found between treatment groups with a lower median in the intensive chemotherapy group (0.6%) compared to hypomethylating agents (8.0%) or supportive care (11.1%) (p <0.0001). In the intensive chemotherapy group, the median overall survival was 34.5 months in patients with iLSC ≤0.10% and 14.6 months in patients with >0.10% (p = 0.031). In the multivariate analyses of this group, iLSC frequency was significantly and independently associated with the incidence of relapse, event-free, relapse-free, and overall survival. However, iLSC frequency had no prognostic impact on patients treated by hypomethylating agents. Thus, the iLSC frequency at diagnosis is an independent prognostic factor in older acute myeloid patients treated by intensive chemotherapy but not hypomethylating agents.

scholarly journals Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Mayumi Sugita ◽  
David C. Wilkes ◽  
Rohan Bareja ◽  
Kenneth W. Eng ◽  
Sarah Nataraj ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Stem Cell Transplant ◽  
Myeloproliferative Neoplasm ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Target Engagement ◽  
Cell Level ◽  
Evaluation And Monitoring ◽  
Acute Myeloid

AbstractThe epichaperome is a new cancer target composed of hyperconnected networks of chaperome members that facilitate cell survival. Cancers with an altered chaperone configuration may be susceptible to epichaperome inhibitors. We developed a flow cytometry-based assay for evaluation and monitoring of epichaperome abundance at the single cell level, with the goal of prospectively identifying patients likely to respond to epichaperome inhibitors, to measure target engagement, and dependency during treatment. As proof of principle, we describe a patient with an unclassified myeloproliferative neoplasm harboring a novel PML-SYK fusion, who progressed to acute myeloid leukemia despite chemotherapy and allogeneic stem cell transplant. The leukemia was identified as having high epichaperome abundance. We obtained compassionate access to an investigational epichaperome inhibitor, PU-H71. After 16 doses, the patient achieved durable complete remission. These encouraging results suggest that further investigation of epichaperome inhibitors in patients with abundant baseline epichaperome levels is warranted.

scholarly journals Long-term survival after intensive chemotherapy or hypomethylating agents in AML patients aged 70 years and older: a large patient data set study from European registries

Leukemia ◽  
2021 ◽  
Author(s):  
Christian Récher ◽  
Christoph Röllig ◽  
Emilie Bérard ◽  
Sarah Bertoli ◽  
Pierre-Yves Dumas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Intensive Chemotherapy ◽  
Hypomethylating Agents ◽  
Term Survival ◽  
Acute Myeloid

AbstractThe outcome of acute myeloid leukemia patients aged 70 years or older is poor. Defining the best treatment option remains controversial especially when choosing between intensive chemotherapy and hypomethylating agents. We set up a multicentric European database collecting data of 3 700 newly diagnosed acute myeloid leukemia patients ≥70 years. The primary objective was to compare overall survival in patients selected for intensive chemotherapy (n = 1199) or hypomethylating agents (n = 1073). With a median follow-up of 49.5 months, the median overall survival was 10.9 (95% CI: 9.7–11.6) and 9.2 months (95% CI: 8.3–10.2) with chemotherapy and hypomethylating agents, respectively. Complete remission or complete remission with incomplete hematologic recovery was 56.1% and 19.7% with chemotherapy and hypomethylating agents, respectively (P < 0.0001). Treatment effect on overall survival was time-dependent. The Royston and Parmar model showed that patients treated with hypomethylating agents had a significantly lower risk of death before 1.5 months of follow-up; no significant difference between 1.5 and 4.0 months, whereas patients treated with intensive chemotherapy had a significantly better overall survival from four months after start of therapy. This study shows that intensive chemotherapy remains a valuable option associated with a better long-term survival in older AML patients.

Sign in / Sign up

Export Citation Format

Share Document