With Prof. Pavel Žák about Current Trends and Future Perspectives in Bone Marrow Transplantation and the Role of Carmustine in this Context

What are the current main trends in the field of bone marrow transplantation for patients with hemato-oncological diseases?

The main trends can be divided as follows:

1. Proper indication and optimal timing in the light of new treatment options, such as bispecific antibodies or CAR-T technology.
2. Donor selection − haploidentical transplants or transplants with a reduced conditioning regimen are routinely implemented.
3. Conditioning regimen, where immunosuppressive therapy with antithymocyte globulin (ATG) is replaced with low-dose cyclophosphamide.
4. Proper treatment of graft-versus-host disease (GvHD) after steroid failure, where the second-line therapy for both acute and chronic GvHD includes ruxolitinib.
5. Utilization of virus-specific lymphocytes in the treatment of Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infections after transplantation.

What is the significance and role of carmustine in the current treatment regimen? Can you mention the advantages and potential disadvantages of this drug compared to other cytostatics?

Carmustine has been and continues to be routinely used in autologous transplants within the BEAM regimen (carmustine, etoposide, cytarabine, melphalan). This regimen is mainly used for autotransplantation of lymphomas, but also in the treatment of other malignancies either in monotherapy or combinational chemoradiotherapy, especially in brain tumors. Its disadvantage is myelosuppression and pulmonary damage – fibrosis usually fatal after 1–3 years. Due to its mechanism, it can induce changes in the DNA of healthy cells and has carcinogenic potential in terms of risk for developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The advantage, however, is its penetration into the CNS.

When to choose the BEAM regimen and when the TEAM (containing thiotepa instead of carmustine)? Are there established protocols for the use of these regimens, and what are the main factors influencing this decision?

Protocols are comparable in terms of toxicity and efficacy. Observations have shown differences without statistical significance, perhaps with a trend towards higher event-free survival in BEAM. The preference for the TEAM regimen in autotransplantations arose from a shortage of carmustine production. TEAM would be preferred in cases of existing pulmonary damage and CNS infiltration as it shows good penetration into the CNS.

What recent studies in the context of bone marrow transplantation do you consider important? Specifically within the pre-transplantation regimen?

This is a broad question. However, I can provide examples from three areas:

• In the area of autologous transplantation BEAM vs. TEAM, I can mention a study focusing on comparing the efficacy and safety of these regimens in autologous stem cell transplantation in lymphoma patients.¹
• Another significant study compared the suitability of haploidentical vs. matched unrelated donors for patients with acute lymphoblastic leukemia (ALL), showing that donor age has a more significant impact than donor type.²
• In the area of immunosuppressive therapy for corticosteroid-resistant GvHD, an interesting meta-analysis presented outcomes on the effect of ruxolitinib in treating acute and chronic graft-versus-host disease in children.³

What do you see for the future of bone marrow transplantation, and what are the challenges?

Allogeneic transplantation remains the main therapeutic modality for acute leukemias and bone marrow failure syndromes or myelodysplastic syndrome. Autologous transplantation will decline as the effectiveness of bispecific antibodies and CAR-T protocols in treating lymphomas and myelomas appears safer and more effective. The main challenge is to emphasize procedure safety and better manage complications, particularly preventing disease relapse, infections, and graft-versus-host reactions.

What treatment modalities are available as alternatives for patients with hematological malignancies who are not suitable for bone marrow transplantation?

As previously mentioned, these include tyrosine kinase inhibitors, bispecific antibodies, and cell therapies.

What are the prospects for using new technologies, such as gene therapy, in this area?

They are indeed crucial! CAR-T cell therapy is now routinely used in the Czech Republic for indications such as diffuse large B-cell lymphoma (DLBCL), selected types of B-ALL, and indolent lymphomas. Its efficacy in other areas is being investigated in studies, with multiple myeloma showing the most promising uses.

MUDr. Andrea Skálová
editorial team, proLékaře.cz

References:
1. Deveci B., Ateşoğlu E. B., Bayrak E. et al. Comparative efficacy and safety of BEAM and TEAM conditioning regimens for autologous stem cell transplantation in lymphoma patients. Transplant Proc 2023; 55 (1): 235−241, doi: 10.1016/j.transproceed.2022.12.001.
2. Mehta R. S., Marin D., Alousi A. et al. Haploidentical vs matched unrelated donors for patients with ALL: donor age matters more than donor type. Blood Adv 2023; 7 (8): 1594−1603, doi: 10.1182/bloodadvances.2022009240.
3. Baccelli F., Gottardi F., Muratore E. et al. Ruxolitinib for the treatment of acute and chronic graft-versus-host disease in children: a systematic review and individual patient data meta-analysis. Bone Marrow Transplant 2024 Feb 24. doi: 10.1038/s41409-024-02252-z [Epub ahead of print].