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Purpose: To describe a bilateral macular detachment as the only sign of acute lymphoblastic leukemia relapse and prompt reversal with total body irradiation without ocular protection. Observations: We present the case of a 20-year-old patient, diagnosed with a high-risk phy-negative, pre-B acute lymphoblastic leukemia (ALL), with a positive MLL gene rearrangement. After a Berlin-Frankfurt-Munster-like regimen chemotherapy protocol and a first complete remission, ALL relapse was diagnosed, so he was commenced on a FlaG-Ida protocol (fludarabine, idarubicin, granulocyte-colony stimulating factor, and high-dose cytarabine). He achieved a second complete remission with positive minimal residual disease and was scheduled for urgent allogeneic bone marrow transplant.Five days before the conditioning regimen was initiated, the patient complained of visual loss in the left eye and then in the right eye. Ophthalmological evaluation showed a best corrected visual acuity of the right eye (OD) of 20/100 and of the left eye (OS) of 20/400. Optical coherence tomography (OCT) showed a bilateral serous sub-foveal detachment. The sub-foveal choroidal thickness was measured by enhanced depth imaging (EDI-OCT) and showed a significant increase (OD 836 μm and OS 1036 μm) compared with normal (average 310 μm). This choroidal thickness increase, associated with the serous macular detachment, was interpreted as a choroidal leukemic infiltration.A lumbar puncture with cytologic studies and flow cytometry was performed, showing no evidence of central nervous system (CNS) involvement of leukemia. CNS and orbital magnetic nuclear resonance imaging showed no pathology. No extramedullary involvement could be confirmed.Retinal fluorescein angiography showed multiple and diffuse leakage points (pinpoint pattern) within the macular area. This pattern reinforced our presumptive diagnosis, even though the lumbar puncture and flow cytometry were negative.The hematologist decided to proceed with the bone marrow transplant. A myeloablative conditioning regimen was delivered, based on total body irradiation (TBI) with a total dose of 12 Gy plus fludarabine 30 mg/m2 for five days. No ocular protection was used during TBI.Only 2 h after TBI commenced, the patient reported a significant improvement in his visual acuity. We confirmed 20/20 in both eyes. The OCT showed a dramatic decrease in the choroidal thickness measurement (OD 387 μm and OS 408 μm compared with 836 μm and 1036 μm measured before radiotherapy). Conclusions and importance: Complete ophthalmological evaluation and EDI-OCT choroidal thickness measurement could be fundamental tools necessary to determine CNS involvement of ALL, even in cases with negative cerebrospinal fluid and brain imaging.

Background Many genetic factors play major roles in the outcome of hematopoietic stem cell transplants from unrelated donors. Transforming growth factor β1 is a member of a highly pleiotrophic family of growth factors involved in the regulation of numerous immunomodulatory processes.Design and Methods We investigated the impact of single nucleotide polymorphisms at codons 10 and 25 of TGFB1, the gene encoding for transforming growth factor β1, on outcomes in 427 mye-loablative-conditioned transplanted patients. In addition, transforming growth factor β1 plasma levels were measured in 263 patients and 327 donors.Results Patients homozygous for the single nucleotide polymorphism at codon 10 had increased non-relapse mortality (at 3 years: 46.8% versus 29.4%, P=0.014) and reduced overall survival (at 5 years 29.3% versus 42.2%, P=0.013); the differences remained statistically significant in multivariate analysis. Donor genotype alone had no impact, although multiple single nucleotide polymorphisms within the pair were significantly associated with higher non-relapse mortality (at 3 years: 44% versus 29%, P=0.021) and decreased overall survival (at 5 years: 33.8% versus 41.9%, P=0.033). In the 10/10 HLA matched transplants (n=280), recipients of non-wild type grafts tended to have a higher incidence of acute graft-versus-host disease grades II-IV (P=0.052). In multivariate analysis, when analyzed with patients’ genotype, the incidences of both overall and grades II-IV acute graft-versus-host disease were increased (P=0.025 and P=0.009, respectively) in non-wild-type pairs.Conclusions We conclude that increasing numbers of single nucleotide polymorphisms in codon 10 of TGFB1 in patients and donors are associated with a worse outcome following hematopoietic stem cell transplantation from unrelated donors.