Why are platines (platinum-based chemotherapeutic agents) not typically used in the conditioning regimen for stem cell allogenic transplants?

From the Guidelines

Platines are not used in the conditioning of a stem cell allogenic transplant due to their toxicity profile and lack of immunosuppressive effects, making them less suitable for balancing cytoreduction and immunosuppression compared to traditional agents like alkylating agents, antimetabolites, and total body irradiation. The primary concern with platines, such as cisplatin, carboplatin, and oxaliplatin, is their significant nephrotoxicity, ototoxicity, and neurotoxicity, which can exacerbate the already substantial toxicities associated with transplant conditioning 1.

The mechanism of action of platines, which involves forming DNA crosslinks that primarily affect rapidly dividing cells, does not provide the comprehensive immunosuppressive effects necessary for successful engraftment in allogeneic stem cell transplants. In contrast, conditioning regimens that utilize alkylating agents (busulfan, cyclophosphamide, melphalan), antimetabolites (fludarabine), and total body irradiation are preferred because they better balance the dual goals of cytoreduction and immunosuppression, with more predictable side effect profiles and established dosing protocols 1.

Key considerations in the choice of conditioning regimen include:

• The need for effective cytoreduction to eliminate malignant cells
• The requirement for immunosuppression to prevent graft rejection
• The potential for toxicity and the impact on patient morbidity and mortality
• The importance of achieving a graft-versus-leukemia (GvL) effect without causing graft-versus-host disease (GvHD)

Given these considerations, the use of platines in conditioning regimens for allogeneic stem cell transplants is not recommended due to their unfavorable toxicity profile and lack of immunosuppressive effects, as supported by recent clinical guidelines and studies 1.

From the Research

Conditioning Regimens for Allogeneic Stem Cell Transplants

The choice of conditioning regimen for allogeneic stem cell transplants is crucial for the success of the transplant. The regimen should provide sufficient cytoreduction to allow for donor cell engraftment while minimizing toxicity to the recipient.

Platinum-Based Chemotherapeutic Agents

Platinum-based chemotherapeutic agents, such as platines, are not typically used in the conditioning regimen for stem cell allogenic transplants. This is because:

• There is limited data on the use of platines in this setting, and other agents have been shown to be effective and safer 2.
• The use of platines may increase the risk of toxicity and non-relapse mortality, which is a major concern in allogeneic stem cell transplantation 3, 4.
• Other conditioning regimens, such as fludarabine and busulfan, have been shown to be effective and well-tolerated in allogeneic stem cell transplantation 5, 6.

Alternative Conditioning Regimens

Alternative conditioning regimens, such as fludarabine and busulfan, or cyclophosphamide and total body irradiation, are commonly used in allogeneic stem cell transplantation. These regimens have been shown to be effective in providing cytoreduction and allowing for donor cell engraftment, while minimizing toxicity to the recipient.

• Fludarabine and busulfan have been shown to be a well-tolerated and effective conditioning regimen for allogeneic stem cell transplantation, with low rates of non-relapse mortality and graft-versus-host disease 3, 5.
• Cyclophosphamide and total body irradiation is another commonly used conditioning regimen, which has been shown to be effective in providing cytoreduction and allowing for donor cell engraftment 5.

Key Points

• Platines are not typically used in the conditioning regimen for stem cell allogenic transplants due to limited data and potential toxicity.
• Alternative conditioning regimens, such as fludarabine and busulfan, or cyclophosphamide and total body irradiation, are commonly used and have been shown to be effective and well-tolerated.
• The choice of conditioning regimen should be individualized based on the patient's disease, age, and other factors, and should be guided by the available evidence and clinical expertise 2, 3, 4, 5, 6.