Experts Identify Factors for Poor Prognosis in Shwachman-Diamond Syndrome With MDS or AML

Study findings suggest that patients with Shwachman-Diamond syndrome and myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) have a poor prognosis because of therapy-resistant disease and treatment-related toxicities (Lancet Haematol. 2019 Dec 23. Epub ahead of print).

“Data to inform surveillance and treatment for leukaemia predisposition syndromes are scarce and recommendations are largely based on expert opinion,” explained Kasiani C. Myers, MD, Department of Pediatrics, University of Cincinnati College of Medicine, Ohio, and co-investigators, who conducted a retrospective, multi-center cohort study to evaluate the clinical features and outcomes of patients with Shwachman-Diamond syndrome and MDS or AML.

The study was carried out in collaboration with the North American Shwachman-Diamond Syndrome Registry and included patient data gathered from 17 centers across the United States and Canada. Patients were eligible for inclusion in the study if they had a genetic or clinical diagnosis of Shwachman-Diamond syndrome and MDS or AML.

Dr Myers et al reviewed the patient records between March 1, 2001, and October 5, 2017, and set out to describe the clinical features and overall survival (OS) rates of these patients.

Of 37 patients initially identified for inclusion, 27 had samples for central pathology review available and were reclassified accordingly, 10 had no samples available and were classified based on the local review data, and 1 patient was excluded.

The remaining 36 patients were included in the analysis, of whom 10 (28%) and 26 (72%) initially presented with AML and MDS, respectively. With a median follow-up of 4.9 years, patients with MDS and AML had a median OS rate of 7.7 years (95% CI, 0.8 to not reached) and 0.99 years (95% CI, 0.2-2.4), respectively; the 3-year OS was 51% (95% CI, 29-68) and 11% (95% CI, 1-39), respectively.

According to the investigators, management and surveillance were flexible. Among the patients with MDS, 18 (69%) received upfront therapy, including 14 who underwent hematopoietic stem cell transplantation (HSCT) and 4 who received chemotherapy; 4 (15%) received no treatment; 2 (8%) had no data available; and 2 (8%) progressed to AML before receiving therapy.

Accounting for the 2 patients who progressed to AML after being diagnosed with MDS, a total of 12 patients received treatment for AML, including 2 (16%) who underwent HSCT as initial therapy and 10 (83%) who received chemotherapy with intent to proceed with HSCT.

Of all the patients included in the study, 33 (92%) had Shwachman-Diamond syndrome before they developed myeloid malignancy and could have been monitored with bone marrow surveillance.

Overall, 3 (33%) of 9 patients with leukemia for whom surveillance status was confirmed and 11 (46%) of 24 patients with MDS had bone marrow surveillance before myeloid malignancy diagnosis. Patients who underwent surveillance (n = 14) had a 3-year OS of 62% (95% CI, 32-82) versus 28% in those who were not monitored (n = 19; 95% CI, 10-50; P = .13).

“Our results suggest that prognosis is poor for patients with Shwachman-Diamond syndrome and myelodysplastic syndrome or acute myeloid leukaemia owing to both therapy-resistant disease and treatment-related toxicities,” Dr Myers and colleagues concluded.

“Improved surveillance algorithms and risk stratification tools, studies of clonal evolution, and prospective trials are needed to inform effective prevention and treatment strategies for leukaemia predisposition in patients with Shwachman-Diamond syndrome,” they added.—Hina Porcelli