Successful allogeneic bone marrow transplantation for myelodysplastic syndrome complicated by severe pulmonary alveolar proteinosis

Abstract

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the abnormal accumulation of alveolar surfactant protein in alveolar spaces. We report herein a rare case of myelodysplastic syndrome (MDS-RAEB) complicated by severe PAP, and successful allogeneic bone marrow transplantation (BMT) for both disorders. An unrelated BMT was planned for a 48-year-old male with advanced MDS-RAEB. Just before the initiation of the conditioning regimen for unrelated BMT in March 2007, he developed dyspnea. A diagnosis of PAP was made based on findings of chest X-ray, CT scanning, and the fluid obtained by bronchoalveolar lavage. To improve his dyspnea and improve BMT safety, whole lung lavage (WLL) was performed twice, with the partial improvement of PAP. Unrelated allogeneic BMT was performed in September 2007. We had to perform a third WLL because of the worsening of PAP on day 26 after BMT. Despite many infectious complications after BMT, GVHD was relatively mild. PAP had almost disappeared 6 months after BMT. He was well with favorable hematopoiesis 20 months after the BMT without any specific treatment. There has been no report of an MDS patient with PAP in whom 3 WLL procedures were performed before and after allogeneic BMT.

Pulmonary alveolar proteinosis

“…Regardless, the haematological disease must be controlled [59,63]. Double symptomatic and aetiological therapy is probably justified, and numerous cases of recovery have been reported after this double therapy [65].…”

Secondary pulmonary alveolar proteinosis in hematologic malignancies

“…6,18,25,28 PAP has been described after autologous hematopoietic stem cell transplantation (autoSCT), 26 and following allo-SCT utilizing matched unrelated donor (MUD), 27 matched related donor (MRD), 28 and unrelated umbilical cord blood transplantation (UCBT). 29 HPAP diagnosed prior to stem cell transplantation has reported response to the successful treatment of underlying myeloid malignancies using autoSCT, 30 reduced intensity conditioning (RIC) allo-SCT using MRD 28 and MUD, 31,32 and myeloablative unrelated UCBT. 33 Though conditioning regimens have long been suspected to play a contributory role in PAP, these observations suggest that neither autologous nor allogeneic transplantation lead directly to the development of PAP, but can induce remission for both conditions in selected patients.…”

“…In patients with HPAP, RIC-allo-SCT is probably more desirable over myeloablative conditioning regimen due to minimal pulmonary toxicity and lower risk of pulmonary infections following RIC-allo-SCT. 31,32 Based on the limited number of small retrospective observational case series, it appears that the presence of HPAP adversely affects outcomes of patients with hematologic malignancies with median survival of less than two years, with most deaths occurring within one year of diagnosis 5,6,18,31 (Table 3), and several deaths attributed to respiratory failure from underlying PAP.…”

“…Isolated reports on utilizing whole lung lavage and GM-CSF while awaiting transplant or after the transplant have shown only modest effect. 32 Due to the invasive nature of whole lung lavage and need for frequent lavages, it is unclear if this intervention is feasible and safe in hematologic malignancy and bone marrow transplant patients. In primary PAP, there are reports of response using rituximab 34 to decrease production of GM-CSF autoantibodies, or plasmapheresis 35 to remove autoantibodies.…”

Secondary Pulmonary Alveolar Proteinosis Following Treatment with Azacitidine for Myelodysplastic Syndrome

“…The emergence of sPAP is observed not only at the diagnosis of MDS but also under various clinical conditions (8)(9)(10)(11)(12). A previous study showed the development of sPAP at the time of disease progression after treatment with cytotoxic agents (10); however, limited information is currently available on the emergence of sPAP in MDS patients treated Intern Med 59: 1081-1086, 2020 DOI: 10.2169/internalmedicine.3770-19 We herein report a case of MDS/sPAP that was diagnosed during treatment with azacitidine for high-risk MDS.…”