Rare Blood Disorders and Hematopoietic Stem Cell Transplantation

Rare Blood Disorders and Hematopoietic Stem Cell Transplantation2020-12-07T14:55:16+01:00

Brigitte Strahm, MD

Program Director, Pediatric Stem Cell Transplantation
Deputy Medical Director, Department of Pediatric Hematology and Oncology

E: brigitte.strahm@uniklinik-freiburg.de
T: +49 761 270 46280
F: +49 761 270 46282

Medical Center – University of Freiburg
Center for Pediatrics
Department of Pediatric Hematology and Oncology
Mathildenstraße 1
79106 Freiburg

Acquired and inherited bone marrow failure syndromes as well as myelodysplastic syndromes encompass a broad spectrum of rare hematological disorders frequently presenting in childhood.  Hematopoietic stem cell transplantation, a potentially curative treatment option is associated with a high risk of acute and late toxicity. Our research focuses on diagnostic and therapeutic strategies to critical define the indication, time point and conditioning regimen for stem cell transplantation and the impact on long term outcomes.


Severe Aplastic Anemia 

Severe aplastic anemia (SAA) is a rare acquired hematological disorder characterized by hypocellular bone marrow and pancytopenia in the peripheral blood. The differential diagnosis of hypocellular bone marrow disorders is challenging and includes inherited bone marrow failure syndromes as well as myelodysplastic syndromes. In SAA, T-cell mediated destruction of hematopoietic stem cells has been shown to be the main pathophysiological mechanism and about 50% of patients respond to immunosuppressive therapy. Allogeneic stem cell transplantation is a curative treatment approach that has traditionally been applied in patients with a matched sibling donor or non-responders to immunosuppressive therapy. We aim to improve patient outcomes with a) a better diagnostic work-up to exclude patients with inherited bone marrow failure syndromes (i.e. dyskeratosis congenita) b) the definition of prognostic markers for response to immune suppressive therapy and c) improved transplant strategies. The network of the European Working Group for Severe Aplastic Anemia (EWOG-SAA) offers a unique chance to address these questions.

Hematopoietic Stem Cell Transplantation (HSCT) for myelodysplastic syndromes and bone marrow failure syndromes 

Myelodysplastic Syndromes (MDS) are a heterogeneous group of disorders characterized by bone marrow dysplasia, cytopenias in peripheral blood and the risk to develop myeloid malignancies. Hematopoietic stem cell transplantation is a curative treatment for patients with MDS, and EWOG-MDS has developed stem cell transplantation guidelines for patients with MDS (https://ewog-mds.de/studies.html). In the current guidelines the indication for HSCT and more specifically the choice of the conditioning regimen depends on the hematological presentation, MDS subtype and karyotype. Our aim is to assess the impact of new diagnostic insights on HSCT outcomes and optimize the HSCT procedure.


  • Ayami Yoshimi, PD Dr. med. (Deputy Chair EWOG-SAA)
  • Luca Vinci, Dr. med. (Study Phyiscian EWOG-MDS/SAA)
  • Silvia Rathmann, Dr. hum. biol. (Project Coordinator EWOG-MDS/SAA)
  • Maria Siskou Zwecker (Data Manager)
  • Anne Breier (Medical Documentation)
  • Wilfried Truckenmüller (Medical Documentation)
  • Peter Noellke, Dipl. Ing (Staticstician)


Telomere length in Severe Aplastic Anemia

The differential diagnosis of acquired aplastic anemia encompasses inherited bone marrow failure syndromes such as dyskeratosis congenital (DC). Premature telomere shortening caused by mutations in genes involved in telomere elongation or maintenance is the cause of the clinical manifestation of DC. However, there are other pathophysiological mechanisms such as regenerative stress or DNA damage that possibly contribute to telomere shortening. With the EWOG-SAA registry (EWOG-SAA 2010) we perform telomere length analysis in patients diagnosed with SAA with the aim a) to identify patients with unrecognized DC and b) analyze the association of telomere length with response to immunosuppressive therapy.

Impact of GATA2 germline mutations on HSCT outcome in MDS 

Genetic research has resulted in the identification of new predisposition syndromes caused by germline mutation in GATA2 or SAMD9/L.  In our cohort of children and adolescents with MDS, germline GATA2 mutations have been identified in 7% of patients with MDS and 15% of patients with advanced MDS. In these patients, HSCT procedures have been applied in accordance with the current recommendation of EWOG-MDS using the hematological manifestation, the karyotype and the MDS subtype, but not the underlying germline mutation for stratification.  The impact of the underlying GATA2 germline mutation on HSCT outcomes will be analyzed.

HSCT with a reduced toxicity conditioning regimen in MDS-RCC

We have previously shown that patients with refractory cytopenia of childhood (RCC) have a low risk of relapse following HSCT and can successfully be transplanted with a reduced intensity regimen. However, the procedure was associated with a considerable risk of relapse. We now investigate whether a low toxicity conditioning regimen offers reliable engraftment combined with the expected low toxicity for patient with RCC.

HSCT in bone marrow failure syndromes

HSCT offers the potential to cure the hematological manifestations in patients with an inherited bone marrow failure syndrome (IBMFS). However, the procedure is generally associated with a considerable risk of early and late morbidity which maybe even more pronounced in IBMF patients. IBMFS are rare and there are virtually no controlled clinical trials for HSCT in patients with IBMFS. Data collection in and detailed analysis of clinical registries therefore offers a unique chance to provide a scientific basis for treatment decisions. Analyzing the data of the French and the German registry for Diamond Blackfan Anemia we were able to demonstrate a favorable outcome for DBA patients being transplanted from a matched sibling or a matched unrelated donor. These results will be incorporated in future clinical guidelines.


BMBF consortium „MyPred“ (Information in German)



  1. Kozyra EJ, Pastor VB, Lefkopoulos S, Sahoo SS, Busch H, Voss RK, et al. Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency. Leukemia. 2020;34(10):2673-87.
  2. Strahm B, Loewecke F, Niemeyer CM, Albert M, Ansari M, Bader P, et al. Favorable outcomes of hematopoietic stem cell transplantation in children and adolescents with Diamond-Blackfan anemia. Blood Adv. 2020;4(8):1760-9.
  3. Locatelli F, Strahm B. How I treat myelodysplastic syndromes of childhood. Blood. 2018;131(13):1406-14.
  4. Wlodarski MW, Hirabayashi S, Pastor V, Stary J, Hasle H, Masetti R, et al. Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents. Blood. 2016;127(11):1387-97.
  5. Peffault de Latour R, Peters C, Gibson B, Strahm B, Lankester A, de Heredia CD, et al. Recommendations on hematopoietic stem cell transplantation for inherited bone marrow failure syndromes. Bone Marrow Transplant. 2015;50(9):1168-72.
  6. Yoshimi A, Niemeyer CM, Fuhrer MM, Strahm B. Comparison of the efficacy of rabbit and horse antithymocyte globulin for the treatment of severe aplastic anemia in children. Blood. 2013;121(5):860-1.
  7. Strahm B, Nollke P, Zecca M, Korthof ET, Bierings M, Furlan I, et al. Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study. Leukemia. 2011;25(3):455-62.
  8. Strahm B, Locatelli F, Bader P, Ehlert K, Kremens B, Zintl F, et al. Reduced intensity conditioning in unrelated donor transplantation for refractory cytopenia in childhood. Bone Marrow Transplant. 2007;40(4):329-33.
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