Editor's Note: Mucormycosis is a group of rare and highly invasive fungal diseases, and its combination with allogeneic hematopoietic stem cell transplantation increases the difficulty of diagnosis and treatment. Previously, the difficulty in rapidly diagnosing mucormycosis often led to poor prognosis in patients with transplantation-associated mucormycosis. At the 50th European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting, Dr. Xu Fang from Professor Yue Lu 's team at Hebei Yanda Lu Daopei Hospital reported a recent clinical study that analyzed the characteristics and prognostic factors of patients with allogeneic hematopoietic stem cell transplantation combined with mucormycosis.Study Methods
The study retrospectively analyzed 4,303 cases of allogeneic hematopoietic stem cell transplantation completed at Hebei Yanda Lu Daopei Hospital from January 1, 2019, to December 31, 2022, focusing on patients with concurrent mucormycosis.
Study Results
The study identified 53 patients with mucormycosis (1.23%), including 46 clinical diagnoses and 7 confirmed cases. There were 29 males and 24 females with a median age of 31 years (range 3-65). Primary diseases included 23 cases of acute myeloid leukemia, 14 cases of acute lymphoblastic leukemia, 6 cases of myelodysplastic syndrome, 5 cases of aplastic anemia, and 5 cases of other hematologic disorders. Transplant types included haploidentical transplants in 39 cases, unrelated donor transplants in 10 cases, and sibling matched transplants in 4 cases.
Infections occurred within one month before the transplant in 8 cases and after the transplant in 45 cases, with a median infection time of 133 days (range 0-910). Pathogens included Rhizopus spp. (n=25), Rhizomucor spp. (n=16), Absidia spp. (n=7), Cunninghamella spp. (n=4), and Mucor spp. (n=1). All pathogens were identified through metagenomic next-generation sequencing (mNGS), primarily from blood samples in 41 cases, sterile tissue in 6 cases, and other non-sterile sites (including bronchoalveolar lavage fluid, sputum, etc.) in 10 cases, with a median sequence count of 150 (range 3-46276) in blood NGS. Only one patient had a positive culture. Infection sites mainly included the lungs in 39 cases, disseminated infection in 6 cases, rhino-orbital-cerebral in 5 cases, gastrointestinal in 2 cases, and cutaneous-soft tissue in 1 case, with central nervous system involvement in 6 cases. Clinical presentations were predominantly fever, accounting for 85%.
All patients had antifungal prophylaxis prior to infection, with azole drugs accounting for 71.7%. During fungal infection, 25 patients were in a neutropenic state, and 19 had acute or chronic GVHD, while others had relapse, thrombotic microangiopathy, viral infections, etc. Combined treatment was given in 43 cases (amphotericin + posaconazole/isavuconazole), and monotherapy in 10 cases, including surgical treatment in 6 cases. The overall treatment response rate was 52.8%.
As of July 1, 2023, the median follow-up time was 65 days (range 1-1422), with an overall survival at 30 days after diagnosing mucormycosis of 60.4±6.7% and a 2-year overall survival of 31±6.5%. A total of 36 deaths occurred, with causes including fungal infection (21 cases), relapse (6 cases), GVHD (6 cases), bacterial infection (1 case), viral encephalitis (1 case), and gastrointestinal bleeding (1 case).
Further univariate analysis suggested that disseminated infection (P=0.03), central nervous system invasion (P<0.01), second transplantation (P=0.03), concurrent GVHD (P=0.01), and neutropenic state (P=0.03) were factors associated with poor prognosis, while surgical treatment (P=0.012) indicated a better prognosis. Multivariate analysis found that central nervous system invasion (P=0.001) and second transplantation (P=0.004) were independent risk factors leading to poor prognosis.
Study Conclusion
The overall prognosis of allogeneic hematopoietic stem cell transplantation combined with mucormycosis is poor. mNGS can rapidly identify pathogens, and central nervous system invasion and second transplantation indicate poor prognosis.
Corresponding Author
Professor Yue Lu
Chief Physician of Hematopoietic Stem Cell Transplantation at Lu Daopei Hospital (Vice-President Level)
Beijing Hematology Association Director
Member of the Hematopoietic Stem Cell Transplantation Application Group, Chinese Medical Association
Member of the Hematology Committee of the Cross-Strait Medical and Health Exchange Association
Clinical training at the Fred Hutchinson Cancer Research Center in Seattle, USA, in October 2016
As of the end of 2023, has completed over 1,500 cases of allogeneic hematopoietic stem cell transplantation
Has published over 10 SCI articles in journals such as Frontiers in Immunology, British Journal of Haematology, Bone Marrow Transplantation, and Biology of Blood Marrow Transplantation.
First Author
Xu Fang
Deputy Chief Physician of Hematopoietic Stem Cell Transplantation at Lu Daopei Hospital
Graduated from Chongqing Medical University’s Clinical Medicine Department in 2007 and received a Master of Medicine from Sun Yat-sen University’s Medical Department in 2010. During his master’s studies, he primarily conducted research on hematological diseases. After graduation, he joined the medical team of Academician Lu Daopei, focusing on allogeneic hematopoietic stem cell transplantation. Skilled in the clinical diagnosis and treatment of common hematological diseases such as acute leukemia, chronic granulocytic leukemia, aplastic anemia, myelodysplastic syndrome, and paroxysmal nocturnal hemoglobinuria. Has extensive experience in managing early and late complications post-transplantation. Has participated in numerous national and international hematology conferences and has presented several posters.
