scholarly journals Outcomes of Acute Lymphoblastic Leukemia with KMT2A (MLL) rearrangement - The MD Anderson Experience

2021 ◽  
Author(s):  
Guillaume Richard-Carpentier ◽  
Hagop M Kantarjian ◽  
Guilin Tang ◽  
C. Cameron Yin ◽  
Joseph D. Khoury ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Poor Prognosis ◽  
Stem Cell Transplant ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cell Transplant ◽  
Md Anderson ◽  
The Impact

Acute lymphoblastic leukemia (ALL) with t(4;11)(q21;q23) - KMT2A-AFF1 is associated with a poor prognosis. The impact of KMT2A rearrangements other than t(4;11) is uncertain and the benefit of allogeneic stem cell transplant (HSCT) is unclear. We reviewed adult patients with ALL treated at our institution from 1984 to 2019 and identified 50/1102 (5%) with KMT2A rearrangement: 42 (84%) with t(4;11)/KMT2A-AFF1 and 8 (16%) with other gene partners. The median age was 45 years old (range, 18 - 78 years); median white blood cell count was 109.0 x 109/L (range, 0.5 - 1573.0). The complete remission (CR) rate was 88% and the rate of measurable residual disease negativity by flow cytometry at CR was 41% (76% overall during follow-up). At the last follow-up, 14 patients were alive. The 5-year overall survival (OS) rate was 18% (95% CI, 9 - 35%) with no difference between t(4;11) and other KMT2A rearrangements (p=0.87). In a 4-month landmark analysis, the 5-year OS rate was 32% (95% CI, 14 - 70%) in patients who underwent HSCT versus 11% (95% CI, 3 - 39) in others (p=0.10). Our study confirms the poor prognosis of ALL with any KMT2A rearrangement and the role of HSCT in these patients.

scholarly journals T-Cell Acute Lymphoblastic Leukemia—Current Concepts in Molecular Biology and Management

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1621
Author(s):  
Parveen Shiraz ◽  
Waqas Jehangir ◽  
Vaibhav Agrawal
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
De Novo ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cell Transplant ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Children And Young Adults

T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon, yet aggressive leukemia that accounts for approximately one-fourth of acute lymphoblastic leukemia (ALL) cases. CDKN2A/CDKN2B and NOTCH1 are the most common mutated genes in T-ALL. Children and young adults are treated with pediatric intensive regimens and have superior outcomes compared to older adults. In children and young adults, Nelarabine added to frontline chemotherapy improves outcomes and end of consolidation measurable residual disease has emerged as the most valuable prognostic marker. While outcomes for de-novo disease are steadily improving, patients with relapsed and refractory T-ALL fare poorly. Newer targeted therapies are being studied in large clinical trials and have the potential to further improve outcomes. The role of allogeneic stem cell transplant (HSCT) is evolving due to the increased use of pediatric-inspired regimens and MRD monitoring. In this review we will discuss the biology, treatment, and outcomes in pediatric and adult T-ALL.

Philadelphia Positive Acute Lymphoblastic Leukemia (Ph+ ALL), Tawam Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4867-4867
Author(s):  
Arif Alam ◽  
Khaled al Qawasmeh ◽  
Jihad Kanbar ◽  
Masood H Syed ◽  
Amar Lal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Stem Cell Transplant ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Molecular Remission

Abstract Acute lymphoblastic leukemia (ALL) is a relatively rare lymphoid disorder with approximately 11 cases per million persons per year in United States. It is seen more commonly in children however adults are also affected with the median age approximately 39 years. The prognosis is influenced by the age of the patient and genetic findings. Abnormal cytogenetic is present in approximately 80 % of the patients. Philadelphia chromosome t (9;22) is seen in approximately 30 % of adult patients (Ph + ALL) and imparts a poor prognosis. Allogeneic stem cell transplant remains one of the corner stones of therapy along with Tyrosine Kinase Inhibitors TKIs (Imatinib or Dasatinib). Patients who are unable to go for transplant are kept on TKIs and continue consolidation and maintenance chemotherapy. In this retrospective review, we present patients with Philadelphia chromosome positive ALL seen at our institute and their outcomes. Tumor registry data base was searched for adult patients with ALL between January 1st 2010 and June 30th 2015. Forty patients were identified with B cell ALL and ten patients were diagnosed with Ph+ ALL (25 % of the cohort). The median age was 30 years (range 18 - 73 years). Male to female ratio was 4.5:1 Induction therapy was given based on UK ALL protocol. Tyrosine kinase inhibitor (Imatinib) was added when information regarding BCR-ABL translocation status was available. Interestingly 8 out of the 10 Ph+ patients also had CD 20 positive disease and were treated with rituximab in addition to standard chemotherapy and TKI. Two patients were lost from follow-up after receiving initial therapy and achieving remission. Four patients had HLA identical siblings and were able to go for allogeneic stem cell transplant. With a median follow up of 28 months (range 1 to 57 months), 3 of the 4 patients are alive and in complete molecular remission. One patient relapsed 19 months post-transplant and died of complications of a 2nd transplant. The remaining 4 patients were unable to go for allogeneic stem cell transplant. They were treated with Hyper-CVAD regimen and Dasatinib (Rituximab was used in patients with CD 20 positive clone). One patient died of colitis and relapsed ALL (36 months post diagnosis) while the other 3 patients are alive and on active therapy, all being in complete molecular remission. Discussion: This is the first report of incidence, management and outcome of Ph+ ALL from UAE. Ph + ALL contribute to 25 % of the cohort of ALL patients in our center. Majority of this cohort was also CD 20 positive. All patients achieved a complete hematologic remission after induction therapy. However, less than half of the patients were able to go for allogeneic stem cell transplantation as consolidation due to different reasons. Post transplantation use of TKI remains variable. HyperCVAD and Dasatinib appears to be a reasonable but toxic alternative for patients who are unable to go for allogeneic stem cell transplantation with a reported estimated survival of 64 % at 2 years interval. Disclosures No relevant conflicts of interest to declare.

scholarly journals Management of adult Ph-positive acute lymphoblastic leukemia

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 406-413 ◽  
Author(s):  
Sabina Chiaretti ◽  
Robin Foà
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitors ◽  
Stem Cell Transplant ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
The Elderly ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant

Abstract Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has been regarded for decades as the ALL subgroup with the worse outcome. It represents the most frequent genetic subtype of adult ALL, and increases progressively with age. The introduction of tyrosine kinase inhibitors (TKIs) has enabled to obtain complete hematologic remissions (CHRs) in virtually all patients, including the elderly, to improve disease-free survival and overall survival, as well as to increase the percentage of patients who can undergo an allogeneic stem cell transplant (allo-SCT). The current management of adult Ph+ ALL patients relies on the use of a TKI with or without chemotherapy followed by an allo-SCT, which still remains the only curative option. Minimal residual disease screening is permitting not only a better stratification of patients, but has also allowed to reconsider the role of autologous stem cell transplant for a set of patients who do not have a donor or are not eligible for an allo-SCT. At present, clinical challenges are represented by the emergence of resistant mutations, particularly the gatekeeper T315I, for which alternative approaches, comprising novel TKIs or therapies based on the combination of TKI with immunotherapeutic strategies, are being considered in order to overcome resistance.

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