Clinical Case Discussion Forum
To share and enhance best practice management of CML, experts and interested clinicians can discuss difficult or interesting CML cases here. Physicians submit a brief history of the patient and the case for discussion using this forum.
Second Post-Transplant Lymphoid Blast-Phase CML Relapse: Asciminib-Based Maintenance, Persistent MRD, and Limited Salvage Options
Dear Colleagues,
I am a hematologist working at a public hospital in northern Chile, where access to advanced therapies is limited. I would greatly appreciate your advice regarding a particularly challenging patient with recurrent lymphoid blast-phase CML following haploidentical transplantation. My experience with such complex cases is limited, and I would be very grateful to learn from your expertise.
Clinical history 56-year-old male, BCR::ABL1 p210-positive CML. 2021 – Initial diagnosis and transplantation The patient presented with advanced-phase CML and B-lymphoid blast transformation (18% lymphoblasts; CD19+, CD10+, CD20+, CD34+, TdT+). He achieved complete hematologic and molecular remission following R-Hyper-CVAD plus dasatinib and underwent haploidentical allogeneic HSCT from his son in August 2021. He subsequently achieved complete donor chimerism and deep molecular responses. During follow-up, he required multiple TKI changes because of intolerance: * Dasatinib: persistent diarrhea. * Imatinib: edema, rash, and effusions. * Nilotinib: hyperglycemia and gastrointestinal intolerance. * Ponatinib: severe generalized edema, pleural and pericardial effusions, ultimately requiring a pericardial window in June 2026.
July 2025 – First post-transplant lymphoid blast-phase relapse Bone marrow examination revealed 98% B lymphoblasts. No ABL1 kinase domain mutations, including T315I, were detected. He received R-Hyper-CVAD followed by high-dose methotrexate/cytarabine plus ponatinib, achieving morphologic and deep molecular remission. Treatment was complicated by prolonged febrile neutropenia, polymicrobial bacteremia, invasive rhinosinus mucormycosis requiring six weeks of liposomal amphotericin B, neutropenic enterocolitis, respiratory failure, and ICU admission. He subsequently received maintenance with ponatinib, vincristine/prednisone, and intrathecal prophylaxis. Methotrexate and mercaptopurine were initially omitted because of cytopenias. He also received donor lymphocyte infusions (DLI) in December 2025, April 2026, and July 2026.
July 2026 – Second post-transplant lymphoid blast-phase relapse Following discontinuation of ponatinib because of severe toxicity, BCR::ABL1 increased rapidly from 0.015% in June to 3.044% in July 2026. Bone marrow evaluation confirmed recurrent B-lymphoid blast crisis, with approximately 85% blasts (73.25% by flow cytometry), expressing CD19, CD10, and CD34, but CD20-negative at relapse. We initiated salvage treatment with Hyper-CVAD plus asciminib 40 mg twice daily, followed by high-dose methotrexate/cytarabine consolidation while continuing asciminib. Following initial reinduction, marrow flow cytometry showed 7.23% residual leukemic B lymphoblasts, with BCR::ABL1 0.4596%. He received intrathecal methotrexate and cytarabine prophylaxis; CSF examinations remained negative. Unfortunately, further treatment was complicated by profound cytopenias and another episode of severe septic shock requiring vasopressors and high-flow oxygen.
Current status – November 2026 The most recent bone marrow examination (October 27, 2026) demonstrated: * Flow cytometry MRD: 0.51% residual B lymphoblasts, CD19+, CD10+, CD34+, CD20+. * Myeloid blasts: 0.18%. * Latest available BCR::ABL1 p210: 0.327% (September 2026). * Repeat molecular monitoring from October 27 is pending. Most recent CBC (November 3): * Hemoglobin: 7.5 g/dL. * WBC: 2.05 × 10⁹/L. * ANC: 0.96 × 10⁹/L. * Platelets: 51 × 10⁹/L. He remains on asciminib 40 mg twice daily.
Importantly, after multiple life-threatening complications, the patient has clearly expressed that he does not wish to receive further intensive chemotherapy or undergo another ICU admission. His family supports this decision. However, he remains willing to receive lower-intensity therapies aimed at controlling the disease while preserving quality of life.
Questions for discussion:
1. Maintenance strategy Given persistent MRD positivity (0.51%), would you recommend: * Asciminib alone, with close molecular monitoring? * Asciminib plus monthly vincristine/prednisone? * Asciminib plus full POMP maintenance (vincristine, prednisone, methotrexate, and mercaptopurine), adjusted for cytopenias? Would the additional myelosuppression from methotrexate and mercaptopurine be justified in this setting?
2. CNS prophylaxis Given his lymphoblastic phenotype, two blast-phase relapses, and previously negative CSF studies, would you continue scheduled intrathecal prophylaxis? If so, what schedule or total number of administrations would you recommend?
3. MRD-directed treatment Considering that the residual leukemic population remains CD19-positive, would you recommend attempting to obtain blinatumomab now, rather than waiting for overt hematologic relapse? Is there meaningful evidence or clinical experience supporting blinatumomab combined with a TKI, particularly asciminib, in lymphoid blast-phase CML after allo-HSCT?
4. Further DLI After three previous donor lymphocyte infusions, is there still a role for additional DLI in the setting of persistent MRD or renewed molecular progression?
5. Options in the event of another relapse If he develops a third blast-phase relapse, what realistic lower-intensity salvage options would you consider? In particular, would you favor blinatumomab, inotuzumab ozogamicin (if CD22-positive), alternative TKI-based combinations, or reduced-intensity chemotherapy? Would repeat ABL1 kinase domain mutation testing or broader molecular profiling meaningfully influence treatment selection? Final considerations We recognize the extremely poor prognosis associated with repeated lymphoid blast-phase relapse following allogeneic transplantation.
Our main challenge is identifying a reasonable balance between disease control, treatment-related toxicity, and the patient’s clearly expressed preferences. Access to blinatumomab, inotuzumab, CAR-T therapy, and clinical trials is extremely limited in our setting. Asciminib and conventional chemotherapy are currently the main treatments available to us. My central question is whether asciminib alone is sufficient in this situation, or whether adding a less intensive ALL-like maintenance approach could provide meaningful benefit without exposing him to another potentially fatal complication.
I would also be particularly interested in hearing what you would realistically offer if the disease progresses again. Thank you very much for your time and for any recommendations or clinical experience you may be willing to share.
Kind regards - Felipe
Dear Felipe,
It seems quite clear that the patient has requested nothing aggressive and with 2 or more lymphoid BC relapses after allografting, the management is clearly palliative. I would use vincristine, prednisone and MTX/6MP to control counts. The ASC could be continued but I am not sure if it is adding anything. DLI has not worked and moreover could add more toxicity and unless there are CNS symptoms requiring symptom control, would not do LPs. When and not if the disease relapses, what is the intent of a change in therapy? Surely not cure or long-term disease control. What is the role of any change? Symptom control with sustaining best possible QOL is the only option here.
Good luck - Jeff