Ravi Bhatia

From the 2026 National Summit on Hematologic Cancers

Tyrosine kinase inhibitor (TKI) therapy has resulted in a significant reduction in chronic myeloid leukemia (CML)-related mortality. However, the impact of TKIs on the health status of long-term CML survivors remains unstudied. We examined the health status of 62 TKI-treated CML patients who did not receive blood or marrow transplantation (BMT) (CML_TKI; median follow-up: 12.5 y) compared with an unaffected population (303 non-CML controls), and CML patients treated with BMT but without TKI exposure (220 CML_BMT; median follow-up 19.4 y). Participants self-reported general health, functional status, activity limitations, and pre-frailty/frailty. Overall, 71.0% of CML_TKI participants had ≥1 adversely-affected domain vs. 42.6% of non-CML and 65.9% of CML_BMT participants. When compared with the non-CML controls, the CML_TKI cohort was more like to have poor general health (aOR = 4.43, 95%CI = 1.8–10.7), functional impairment (aOR=2.84, 95%CI = 1.4–6.0), and activity limitation (aOR=3.37, 95%CI = 1.7–6.7) and more likely to be frail/pre-frail (aOR=3.71, 95%CI = 1.7–8.1). The CML_TKI and CML_BMT cohorts were comparable with respect to poor general health (aOR = 0.95, 95%CI = 0.5–2.0), functional impairment (aOR = 1.59, 95%CI = 0.8–3.0), and pre-frailty/frailty (aOR = 1.92, 95%CI = 0.92–4.0), but the CML_TKI cohort was more likely to report activity limitation (aOR = 2.2, 95%CI = 1.1–4.5). These findings inform a need for long-term monitoring and development of risk mitigation strategies to improve the health status as a treatment goal in CML care.

Background: Post-remission cytarabine consolidation is a cornerstone of therapy for acute myeloid leukemia (AML), but the optimal dosing strategy in older adults (≥60 years) remains unclear. High-dose cytarabine (HiDAC) is often avoided due to toxicity concerns, and data guiding cumulative dosing are limited. Methods: We conducted a single-center retrospective cohort study of 111 patients aged ≥60 years with AML who achieved complete remission after standard 7 + 3 induction and received at least one cycle of cytarabine consolidation between 2012 and 2024. A 90-day landmark analysis excluded early relapses or deaths. Results: The median age was 65 years; 41% proceeded to allogeneic hematopoietic stem cell transplantation (allo-SCT). Cytarabine consolidation was well tolerated, with no neurotoxicity and only one instance of reversible nephrotoxicity. Patients were stratified by median cumulative cytarabine dose into low-intensity (2, LIC) and high-intensity (≥18 g/m², HIC) groups. HIC was associated with improved overall survival compared with LIC (median OS: 31 vs. 13 months, p = 0.02), particularly among non-transplanted patients (25 vs. 7 months, p = 0.01). On multivariable analysis, HIC (HR 0.71, 95% CI 0.51–0.82, p = 0.01) and allo-SCT (HR 0.58, 95% CI 0.44–0.79, p = 0.03) independently predicted superior survival. Conclusions: Higher cumulative cytarabine consolidation is safe, feasible, and associated with improved survival in older AML patients, especially among patients ineligible for transplant. Prospective studies are warranted to define the optimal dosing strategy in this population.

Allogeneic hematopoietic cell transplantation (allo-HCT) remains a key treatment for patients with chronic myeloid leukemia (CML) in blast phase (CML-BP) or tyrosine kinase inhibitor (TKI)-resistant chronic phase (CML-CP). We retrospectively analyzed 75 patients who underwent allo-HCT at four U.S. centers from 2005 to 2023. Of these, 60 had CML-BP (26 myeloid, 34 lymphoid) and 15 had TKI-resistant CML-CP. Median overall survival (OS) was 50 months in myeloid blast phase (MBP) and not reached in lymphoid blast phase (LBP) or CML-CP. MBP had higher relapse rates and inferior leukemia-free survival (LFS) compared to LBP and CML-CP. Outcomes were worse in transformed MBP versus de novo MBP, and in those with 7/7q- deletions. Post-HCT TKI maintenance did not significantly affect relapse or survival. Our findings support allo-HCT as an effective treatment option in CML-BP and TKI-resistant CML-CP, with outcomes influenced by disease biology and cytogenetic features at transformation.

PURPOSE: There is emerging evidence that germline pathogenic/likely pathogenic (P/LP) mutations in cancer predisposition genes (CPGs) increase the risk of subsequent neoplasms (SNs) in childhood cancer survivors. However, clinical application of this observation is hampered by the lack of knowledge regarding subpopulations at risk for SNs who could potentially benefit from genetic screening. PATIENTS AND METHODS: Whole-exome sequencing was performed using germline DNA from 499 survivors with SNs (cases) and 625 survivors without (matched controls) in a Children's Oncology Group study. Using conditional logistic regression, we estimated demographic/clinical/therapeutic characteristics and P/LP mutations associated with SN risk. We then randomly partitioned the case-control data set using a 60/40 split to create training and test data, respectively, and developed a clinical risk classifier. Model performance and its improvement with addition of P/LP mutation status was evaluated on the test data using the area under the receiver operating curve (AUC). RESULTS: We found a 4.26-fold higher odds of SNs among P/LP mutation carriers (95% CI, 2.36 to 7.69). The clinical risk classifier (including sex, primary cancer type and year of diagnosis, exposure to radiation and platinum compounds, and length of follow-up) showed a significant performance improvement with the addition of P/LP mutation status, and P/LP × platinum and P/LP × radiation interactions (AUC increased from 0.79 to 0.82, P = .014). Using the clinical risk classifier, we classified survivors at low risk (22%) and moderate-to-high risk (78%) of developing SNs. Overall, 86.4% of the survivors with any P/LP mutations, and all TP53 and RB1 mutation carriers were partitioned into the moderate-to-high risk group. CONCLUSION: These findings provide a risk-based approach for identifying childhood cancer survivors who could be referred for genetic testing, informing surveillance strategies on the basis of refined risk classification.

Clonal hematopoiesis is associated with increased risk of venous thromboembolism (VTE). The risk of VTE is high in patients with lymphoma and after autologous peripheral blood stem cell transplantation, and clonal hematopoiesis is present in many patients with lymphoma at autologous peripheral blood stem cell transplantation. We examined whether clonal hematopoiesis increases posttransplant VTE risk in patients with lymphoma. Our study included 557 patients with lymphoma who had survived 2 or more years after receiving autologous peripheral blood stem cell transplantation between 1999 and 2014. Clonal hematopoiesis was measured by targeted sequencing of cryopreserved peripheral blood stem cell product. Median age at stem cell transplantation was 54 years. Subdistribution hazard regression analysis with death as a competing risk was used to examine the association between clonal hematopoiesis in the peripheral blood stem cell product and post–autologous peripheral blood stem cell transplantation VTE. Clonal hematopoiesis was detected in 36.1% of patients. The 8-year cumulative incidence of VTE was 8.2% with clonal hematopoiesis vs 3.6% among patients without clonal hematopoiesis. The presence of PPM1D mutation (hazard ratio = 4.12, 95% CI = 1.55 to 10.92) or TP53 mutation (hazard ratio = 5.31, 95% CI = 1.54 to 18.35), with no clonal hematopoiesis as the referent, was associated with VTE risk in adjusted analysis.

Background: Despite the remarkable efficacy of tyrosine kinase inhibitors (TKIs), patients with chronic myeloid leukemia (CML) often face adverse effects, prompting investigations into treatment-free remission (TFR) for patients with sustained deep responses. Methods: Our objective was to assess real-world outcomes of TFR in a single-center cohort of patients in the southeastern U.S., as well as to compare different TKI management strategies (abrupt cessation of a TKI at a standard dose, TKI dose tapering prior to cessation, or upfront TKI dose reduction followed by abrupt cessation before TFR). Results: We queried our CML database of 233 patients and identified 39 patients that aimed for TFR. The median TFR duration was 14.6 months, with 63% actively remaining in TFR with a median follow-up of 21 m. TFR was lost by 54%, 16%, 8%, and 21% of patients in 0–6 m, 6–12 m, 1–2 y, and >2 y, respectively. Among the three TKI management strategies, the safety outcomes were comparable, with no instances of disease progression or CML-related mortality. All patients who lost TFR successfully regained a major molecular response (MMR) upon the resumption of TKIs. In terms of efficacy, 61%, 59%, and 59% of patients who underwent abrupt cessation of standard-dose TKIs, standard-dose tapering, or upfront dose reduction maintained TFR, respectively. Conclusions: Our study highlights the relative safety of pursuing TFR via different TKI treatment strategies in a real-world setting.