Nonmyeloablative Allogeneic Stem Cell Transplantation With Postcyclophosphamide in a Case of Acute Lymphoblastic...

We report a case of unrelated non-myeloablative allogeneic stem cell transplantation (allo-SCT) incorporating post-transplant cyclophosphamide (PTCy) in an adult patient with acute lymphoblastic leukemia (ALL) complicated by ventricular septal defect (VSD).

A 62-year-old woman presented with pancytopenia and concurrent COVID-19 infection. Bone marrow examination revealed an increased number of CD19+, CD10+, CD34+, HLA-DR+ lymphoblasts, and she was diagnosed with ALL. She had a known membranous-type VSD from childhood, which was confirmed by echocardiography prior to chemotherapy. There were no signs of pulmonary hypertension or heart failure at that time. Given the concurrent infection, initial treatment prioritized managing the infection, followed by corticosteroid therapy with prednisolone and induction chemotherapy. She achieved first complete remission after induction therapy and subsequently underwent consolidation chemotherapy, followed by unrelated non-myeloablative allo-SCT with PTCy conditioning. Post-transplant, she developed stage 2, grade 1 acute graft-versus-host disease (aGVHD) of the skin, but otherwise experienced no major complications. However, the VSD hole diameter gradually increased from 2.6 mm at remission induction to a maximum of 4.7 mm at 6 months post-transplant. At that time, her brain natriuretic peptide (BNP) level rose sharply to 4577 pg/mL, with accompanying elevations in LDH and liver enzymes, indicative of right heart failure and congestive hepatopathy due to VSD enlargement. Treatment with pimobendan, tolvaptan, and spironolactone resulted in BNP reduction to <1000 pg/mL within 6 weeks, and normalization of LDH and liver function prior to the BNP peak. These medications were discontinued 4 months after the onset of right heart failure. By one year post-transplant, the VSD diameter had decreased to 3.5 mm and later stabilized at 3.9 mm.

The patient with ALL complicated by VSD underwent induction chemotherapy followed by unrelated allogeneic nonmyeloablative SCT using a PTCy regimen. From the initiation of chemotherapy (including pre-transplant conditioning) up to 6 months post-transplant, the VSD hole progressively enlarged, leading to the development of right-sided heart failure. However, since post-transplant complications were mild, treatment with diuretics and other supportive measures led to improvement of heart failure. The VSD hole size decreased to some extent but did not return to its pre-treatment dimensions.

In this case of ALL with VSD, the VSD hole diameter continued to enlarge during chemotherapy; however, after pre-transplant conditioning with PTCy, the diameter began to decrease around one year post-transplant, though it did not return to its original size. While careful monitoring is needed for right heart failure due to VSD enlargement, pre-transplant conditioning with PTCy was considered a feasible option for hematologic malignancies complicated by VSD.