Modified transplantation salvages refractory CML after pneumonectomy and CNS relapse
A rare transplant course in chronic myeloid leukemia moved through pulmonary fungal invasion, central nervous system relapse, and ultimately durable remission after a customized allogeneic stem-cell transplant. The case centers on a 55-year-old woman whose disease escaped multiple tyrosine kinase inhibitors, then became even more complex when severe mucormycosis forced a total left pneumonectomy before transplantation could even be considered.
The sequence matters because each complication narrowed the margin for standard treatment. By the time transplant was pursued, the patient had advanced-phase CML, prior invasive fungal infection, central nervous system disease, and poor physiologic reserve after major lung resection. A conventional myeloablative strategy would have carried a heavy toxicity burden in that setting.
Multiple kinase inhibitors failed to hold the leukemia in check
Initial presentation in December 2020 was classic for active myeloproliferative disease: fatigue, low-grade fever, night sweats, weight loss, and marked splenomegaly. Blood counts showed a white blood cell count of 36 × 10^9/L, and bone marrow contained 8% myeloblasts. Cytogenetics confirmed the Philadelphia chromosome, and molecular testing detected BCR::ABL P210 with a transcript level of 12.3%.
Imatinib 400 mg daily was started first. By November 2021, the transcript level had fallen to 2.9%, but therapy was switched to dasatinib. When the patient arrived at Beijing Luhe Hospital in January 2023, BCR::ABL P210 remained detectable at 3.87%, and targeted therapy was changed again to flumatinib 600 mg daily.
Disease control continued to erode. Bone marrow reassessment in January 2024 showed WT1 overexpression, persistent BCR::ABL P210 positivity, and a JAK3 p.R549Q variant. Tofacitinib 5 mg twice daily was added, but bone marrow review on January 11, 2024 confirmed CML blast crisis. Two days later, treatment shifted to azacitidine plus venetoclax, followed on February 13 by azacitidine on days 1–7, venetoclax 100 mg twice daily, and oleracitinib 40 mg every other day.
The biology here is unforgiving. Once CML advances to blast phase, the leukemic clone behaves less like a chronic proliferative disorder and more like an acute leukemia with lineage plasticity, clonal escape, and a much steeper risk of extramedullary spread.
Invasive fungal disease forced a lung resection before transplant could be attempted
During agranulocytosis in March 2024, the patient developed a complicated pulmonary fungal infection. Bronchoalveolar lavage fluid identified organisms from the Bacillus cereus group, Mycobacterium lentiflavum, Cunninghamella bertholletiae, Aspergillus rutilus, and Aspergillus fumigatus. Antibacterial therapy included meropenem, ciprofloxacin, and tigecycline, while antifungal treatment was changed to liposomal amphotericin B plus posaconazole.
Chest CT and bronchoscopy showed progressive pulmonary involvement. After initial stabilization, intermittent hemoptysis emerged, and imaging suggested fungal invasion of pulmonary vessels and large airways. A total left pneumonectomy was performed in April 2024. Follow-up chest CT on August 8, 2024 showed favorable recovery, and the infection remained controlled on later imaging after transplant.
This was not a routine pretransplant complication. Invasive mold disease can become a direct mechanical threat when it erodes airways and vessels, and hemorrhage in that context forces surgical source control before any transplant team can safely intensify immunosuppression.
CNS leukemia appeared after pulmonary recovery
The next turn came in March 2025, when the patient developed progressive morning headache and projectile vomiting unrelated to oral intake. Cerebrospinal fluid opening pressure exceeded 200 mmH2O, CSF white blood cell count was 20 cells/μL, and leukemic blasts were identified. Flow cytometry of the CSF showed a population making up 74.78% of all cells with dim CD45 expression, intermediate-to-large scatter characteristics, and an immunophenotype consistent with myeloid blasts.
Concomitant central nervous system leukemia was diagnosed. Lumbar puncture with intrathecal chemotherapy began on March 25, 2025, along with olverembatinib. Additional lumbar punctures with intrathecal therapy were performed on March 31 and April 2, 2025. Craniospinal irradiation followed using VMAT, delivering 21.6 Gy to the brain and 19.2 Gy to the spinal cord in 10 fractions to each target volume.
By August 18, 2025, bone marrow and CSF examinations showed complete remission, and the quantitative BCR::ABL transcript level had declined to 0.0032%.
Reduced-intensity conditioning balanced cytoreduction and toxicity
Allogeneic transplantation from an HLA 10/10-matched sibling donor was initiated on September 14, 2025. The conditioning regimen combined fludarabine from day -10 to day -6, cytarabine from day -10 to day -9, busulfan from day -8 to day -6, cyclophosphamide from day -5 to day -2, and rabbit anti-human thymocyte globulin from day -3 to day -2. GVHD prophylaxis used sirolimus, mycophenolate mofetil, and low-dose methylprednisolone. Prophylaxis also covered veno-occlusive disease, antiviral infections, fungal infections, and Pneumocystis pneumonia.
The choice of regimen reflected the patient’s risk profile. Prior pneumonectomy, poor physical status, repeated TKI resistance, and CNS leukemia all pushed the team away from a full-intensity myeloablative platform. Fractionated cyclophosphamide is especially relevant in that setting because dividing the total dose can reduce peak exposure and blunt urothelial and cardiac toxicity while preserving antileukemic effect.
Engraftment was prompt: neutrophils recovered on day +11 and platelets on day +13. Chimerism reached 99% donor origin. BK virus-related hemorrhagic cystitis developed on day +30 but improved with hydration, urine alkalinization, tapered immunosuppression, and intravenous immunoglobulin. Epstein-Barr virus reactivation occurred on day +55 and cleared after immunosuppression was reduced.
Durable remission after transplant depended on surveillance as much as conditioning
At more than 9 months of follow-up, the patient remained clinically stable, and serial monitoring showed persistent MRD negativity with undetectable BCR::ABL transcripts. Ponatinib was given for relapse prevention beginning 3 months after transplant and continued for 6 months, although it was later stopped because of intolerance after 2 months of use. Even after discontinuation, multiparameter flow cytometry and molecular testing remained negative through the final follow-up assessment at over 10 months post-transplant.
This case adds a difficult but important signal to transplant practice in CML. Allogeneic transplantation still offers the only curative path for blast-phase disease, yet the route to that cure may require aggressive infection control, organ-sparing judgment, CNS-directed therapy, and conditioning tailored to prior toxicity. The case also shows how quickly the therapeutic target can shift from molecular response to life preservation when fungal disease and extramedullary leukemia appear in the same patient.
Single-case evidence cannot define a standard approach, and this regimen should not be generalized without caution. What it does show is that heavily pretreated CML with CNS involvement and prior pneumonectomy can still reach remission when source control, salvage leukemia therapy, and transplant planning are integrated with unusual precision.