Management of Chronic Myeloid Leukemia During Pregnancy: Review of Evidence and Treatment Algorithm.

Philadelphia chromosome-positive chronic myeloid leukemia (CML) during pregnancy is rare, with an annual incidence of 1 per 100,000 pregnancies. Managing CML in pregnancy is challenging due to concerns about the teratogenicity of the BCR::ABL1 tyrosine kinase inhibitors (TKIs). While some pregnant patients with chronic-phase CML may be managed with close monitoring and no therapy, others, particularly those diagnosed in the first trimester, may require treatment to prevent disease progression and maternal complications.

Outcomes and patterns of relapse with ponatinib-based therapy in patients with chronic myeloid leukemia in myeloid blast phase.

We analyzed 76 patients who received a ponatinib-based regimen, either as monotherapy or in combination with chemotherapy, for chronic myeloid leukemia in myeloid blast phase (CML-MBP). The rate of morphological remission with or without count recovery (i.e.

Contemporary outcomes of octa-nonagenarians with newly diagnosed acute myeloid leukemia.

Background: Octa-nonagenarians with acute myeloid leukemia (AML) represent a high-risk group due to frequently poor performance status, adverse genomics (e.g., TP53 mutations, complex karyotype), a high incidence of secondary AML, and inability to undergo an allogeneic stem cell transplantation.

Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Can Be Treated With Chemotherapy-Free Regimens Without Transplant.

The incorporation of ponatinib into the frontline regimens of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) deepened the molecular responses and improved outcomes. Patients with Ph-positive ALL who achieve a complete molecular response (CMR, undetectable BCR::ABL1 transcripts by RT-PCR) by 3 months of therapy have a better survival compared to those with persistent disease. Studies showed that the next-generation sequencing (NGS) assay, with a sensitivity up to 1 × 10, is more sensitive than RT-PCR for the detection of measurable residual disease (MRD) in Ph-positive ALL and therefore carries a better prognostic value.

Incorporation of Immunotherapy Into Adult B-Cell Acute Lymphoblastic Leukemia Therapy.

Blinatumomab and inotuzumab ozogamicin have demonstrated efficacy in treating relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and improving outcomes compared with conventional chemotherapy. Encouraging results have been observed in both younger and older patients with Philadelphia chromosome (Ph)-positive and Ph-negative B-ALL treated with these immunotherapy agents across several clinical trials. Treatment with inotuzumab ozogamicin and/or blinatumomab leads to high rates of deep measurable residual disease negativity and may enhance survival compared with chemotherapy-only approaches, reducing the need for intensive chemotherapy, and potentially the need for allogeneic stem cell transplantation.

Management of chronic myeloid leukemia in 2025.

Chronic myeloid leukemia (CML) has an annual incidence of approximately two cases per 100,000. The reduction in annual mortality from 10%-20% to 1% with BCR::ABL1 tyrosine kinase inhibitors (TKIs) has resulted in an increased prevalence in the United States of an estimated 150,000 cases in 2025. This translates into a worldwide estimated prevalence of approximately 5 million cases, and hence the need to make TKIs available and affordable to all patients.

Lower-intensity chemo-immunotherapy with cladribine, low-dose cytarabine, venetoclax and blinatumomab produces high response rates in patients with -negative B-cell / myeloid mixed phenotype acute leukemia.

Not available.

Molecular characterization and predictors of relapse in patients with Ph + ALL after frontline ponatinib and blinatumomab.

Background: Several studies have suggested that chemotherapy-free regimens consisting of blinatumomab and a BCR::ABL1 tyrosine kinase inhibitor are highly effective in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, the clinical and molecular characteristics that predict for relapse with these chemotherapy-free regimens are largely unknown.

Methods: We conducted a prospective phase II clinical trial of the combination of blinatumomab and ponatinib in 76 patients with newly diagnosed Ph + ALL.

Treatment of Older Patients With ALL.

Older patients with ALL often have high-risk disease characterized by adverse-risk cytogenetic and molecular abnormalities, as well as Philadelphia chromosome (Ph)-positive and Ph-like phenotypes. They often have comorbidities resulting in poor tolerance to chemotherapy and are at risk of developing therapy-related myeloid neoplasms (t-MNs). In Ph-negative ALL, the duration and intensity of chemotherapy was reduced, and outcomes improved with the addition of inotuzumab ozogamicin (InO) and blinatumomab into the frontline setting.

Characteristics and outcomes of newly diagnosed acute myeloid Leukemia with KMT2A rearrangements.

Acute myeloid leukemia (AML) with KMT2A rearrangement (KMT2Ar) has poor outcomes. We analyzed 1,611 patients with AML and 4.3% demonstrated rearrangements in KMT2A.

Unusually Indolent CML: Absence of Complete Cytogenetic Response after 10 Years of Tyrosine Kinase Inhibitor Therapy.

Background: With BCR::ABL1 tyrosine kinase inhibitor (TKI) therapy, most patients with chronic-phase chronic myeloid leukemia (CML-CP) can achieve complete cytogenetic response (CCyR) within 6 months of therapy. However, no studies have investigated patients who do not achieve CCyR yet maintains stable disease on long-term TKI treatment. Here we investigated 30 CML-CP patients who did not achieve CCyR but remained free of blastic progression for at least 10-year while on TKI therapy.

Inferior Outcomes in Acute Lymphoblastic Leukemia With Translocation (14;18).

Introduction: The (14;18)(q32;q21) chromosomal translocation leading to IGH::BCL2 rearrangement, has been rarely described in B-cell acute lymphoblastic leukemia (B-ALL), mainly in association with MYC rearrangement. The outcome of B-ALL harboring t(14;18)(q32;q21) without MYC rearrangement remains unknown.

Methods: We retrospectively reviewed 2778 cases of B-ALL treated at our institution and identified those harboring a t(14;18)(q32;q21) by karyotype.

Olverembatinib in chronic myeloid leukemia-Review of historical development, current status, and future research.

Once considered an incurable disease with a poor prognosis (median survival, 3-6 years), chronic myeloid leukemia (CML) is now managed with a diverse clinical armamentarium that includes BCR::ABL1 tyrosine kinase inhibitors (TKIs), which have largely normalized life expectancy in most patients in the chronic phase of the disease (CML-CP). Clinical challenges remain, including ABL1 mutation-driven treatment resistance (under the selection pressures exerted by TKIs), as well as treatment intolerance, which can involve potentially serious arterial occlusive events. Olverembatinib is a third-generation TKI approved in China for TKI-resistant CML-CP and accelerated-phase CML with the T135I mutation, as well as for CML-CP resistant to or intolerant of first- and/or second-generation TKIs.

Cladribine, idarubicin, and cytarabine (CLIA) for patients with relapsed and/or refractory acute myeloid leukemia: A single-center, single-arm, phase 2 trial.

Background: The treatment of relapsed and/or refractory (R/R) acute myeloid leukemia (AML) remains challenging because of poor responses to chemotherapy. Efforts to improve outcomes have included the use of high-dose cytarabine in combination with nucleoside analogs, such as cladribine. The authors evaluated combined cladribine, idarubicin, and cytarabine (CLIA) in a phase 2 trial of 66 patients with R/R AML.

Treatment-free remission in nontransplanted patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Background: The BCR::ABL1 tyrosine kinase inhibitors (TKIs) have significantly improved the outcomes of patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, the optimal duration of TKI therapy in patients who achieve a complete molecular response (CMR; undetectable BCR::ABL1 transcripts) and who do not undergo allogeneic stem cell transplantation (allo-SCT) remains undefined.

Methods: The authors conducted a retrospective analysis of patients with Ph-positive ALL in first complete remission who achieved a CMR and discontinued TKI therapy, most commonly due to treatment-related side effects.

Frontline immunotherapeutic combination strategies in adult B-cell acute lymphoblastic leukemia: reducing chemotherapy intensity and toxicity and harnessing efficacy.

Using immunotherapeutic agents like inotuzumab ozogamicin (InO), blinatumomab, or chimeric antigen receptor T (CAR T)-cell therapy in frontline adult B-cell acute lymphoblastic leukemia (B-ALL) therapy is promising. These agents are mostly well tolerated and have different toxicity profiles than conventional chemotherapy, enabling their combination with chemotherapy. Additionally, they have often been shown to overcome the traditional adverse ALL risk features.

Hyper-CVAD and Sequential Blinatumomab Without and With Inotuzumab in Young Adults With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia.

Adding inotuzumab ozogamicin (InO) to hyper-CVAD and blinatumomab may improve outcomes in newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL). Patients with newly diagnosed B-ALL received up to four cycles of hyper-CVAD followed by four cycles of blinatumomab. Beginning with patient #39, InO 0.

Outcomes of Patients With Treated Secondary Acute Myeloid Leukemia: A High-Risk Subtype That Warrants an Independent Prognostic Designation.

Patients who develop acute myeloid leukemia (AML) after having received treatment for myelodysplastic syndrome (MDS) or related conditions have particularly poor outcomes. This study analyzed adult patients with newly diagnosed AML who previously had MDS, chronic myelomonocytic leukemia (CMML), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome, and who had received hypomethylating agents, chemotherapy, and/or allogeneic stem cell transplantation (HSCT) for these antecedent disorders. From January 2012 to August 2023, we included 673 patients with a median age of 70 years (range, 19-94); 536 (80%) had transformed from MDS, and the remainder from CMML or MDS-MPN.

Clinical interrogation of aberrations and its impact on survival in patients with myeloid neoplasms.

In myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with TP53 aberrations, dissecting the interaction amongst patient, disease and treatment factors are important for therapeutic decisions and prognostication. This retrospective analysis included patients with newly diagnosed MDS (>5% blasts) and AML with TP53 mutation(s) treated at MD Anderson Cancer Center. We factored patient age, TP53 aberration burden, therapy intensity and use of venetoclax in the AML subgroup, and allogeneic hematopoietic stem cell transplantation (HSCT) to interrogate outcomes.

Decitabine, venetoclax, and ponatinib for advanced phase chronic myeloid leukaemia and Philadelphia chromosome-positive acute myeloid leukaemia: a single-arm, single-centre phase 2 trial.

Background: Advanced phase Philadelphia chromosome-positive myeloid disease-consisting of chronic myeloid leukaemia in the myeloid blast phase and in the accelerated phase, and Philadelphia chromosome-positive acute myeloid leukaemia-is associated with poor outcomes. Although previous studies have suggested the benefit of chemotherapy and BCR::ABL1 tyrosine kinase inhibitor combinations, the optimal regimen is uncertain and prospective studies for this rare group of diseases are scant. Preclinical and retrospective clinical data suggest possible synergy between the BCL-2 inhibitor venetoclax and BCR::ABL1 tyrosine kinase inhibitors.

A phase 2 trial of mini-hyper-CVD, blinatumomab, and ponatinib in Philadelphia positive acute lymphoblastic leukemia.

Twenty adults with newly diagnosed (ND) or relapsed/refractory (RR) Ph-positive acute lymphoblastic leukemia (ALL), or chronic myeloid leukemia in lymphoid blast phase (CML-LBP), were treated with mini-hyperCVD, ponatinib, and blinatumomab. Complete molecular response was achieved in 78% of ND patients, while CR/CRi was achieved in 100% of RR and CML-LBP. The 3-year overall survival rate was 76% (95% CI, 47%-90%).