Regimens Used for GvHD Prevention

EP: 1.An Overview of Graft vs Host Disease (GvHD)

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EP: 2.Regimens Used for GvHD Prevention

EP: 3.Clinical Implications of the Phase III BMT CTN 1703 Trial

EP: 4.Future of Acute GvHD Prevention

EP: 5.Acute GvHD: Clinical Presentation, Risk Factors and Treatment Options

EP: 6.Steroid Refractory Acute GvHD and REACH Trials

EP: 7.Novel Agents in Acute GvHD

EP: 8.Defining Chronic Graft vs Host Disease (GvHD)

EP: 9.Treatment Options for Chronic GvHD

EP: 10.Treatment Options: Steroid-Refractory GvHD

EP: 11.Future of Chronic GvHD

EP: 12.GvHD: Advice for Patients

Transcript:

Corey Cutler, MD, MPH FRCPC: I’m going to go back to a point you made about trying to separate graft versus leukemia from graft versus host disease [GVHD]. We’ve traditionally used high-intensity conditioning regimens as a way of helping induce that graft versus tumor effect, or at least eradicating a tumor with high doses of chemotherapy and radiation. Doris, what are the major conditioning regimens you use at your center, particularly when you’re looking at myeloablation, or high intensity?

Doris M. Ponce, MD: We use a TBI [total body irradiation]-based regimen, BU-CY [busulfan and cyclophosphamide]. We could use a combination with BU-MEL-FLU [busulfan, melphalan, fludarabine]. As you know, there’s a national shortage of fludarabine, so we’re becoming more creative. Clofarabine is making an entrance in the armamentaria to use as part of our conditioning regimen options. For lymphoid malignancies like ALL [acute lymphocytic leukemia], it’s TBI-based, we’re leaning more into it, and for myeloid, a busulfan-based regimen is part of what we use.

Corey Cutler, MD, MPH FRCPC: Do you think there’s a difference in these myeloablative regimens? Does it matter, BU-CY [busulfan, cyclophosphamide], FLU-BU [fludarabine, busulfan], or BU-MEL [busulfan, melphalan]? Are there differences in toxicity? What do you use at your center?

Hannah K. Choe, MD: Yes, definitely. We do follow a pretty traditional landscape of using fludarabine-busulfan regimens and then, titrating the AUC [area under the concentration time curve] of the busulfan for the degree of myeloablation. In the borderline reduced intensity, FLU-MEL 140 mg, and then lower intensity, FLU-MEL 100 mg. The pretty traditional [landscape] for AMLs [acute myelocytic leukemias] and MDSs [myelodysplastic syndromes]. But that difference between using busulfan versus melphalan comes up particularly for older patients, we’ll tend toward the melphalan. For patients who are at high risk of lung toxicity or liver toxicity, we then avoid busulfan. Generally, those are our preferences there.

Corey Cutler, MD, MPH FRCPC: Once we’ve cleared out the patient of their own marrow cells, we need to give them some stem cells back, and that’s the time when we have to prevent graft versus host disease. I’m going to give you 2 scenarios. I’m going to ask you pre-ASH [American Society of Hematology annual meeting] and post-ASH, what is the preferred or standard GVHD prevention regimen that you use at Massachusetts General Hospital in the pre-ASH setting?

Yi-Bin Chen, MD: Do you want to specify donor, or disease?

Corey Cutler, MD, MPH FRCPC: Let’s talk about a standard scenario, a matched related or a matched unrelated donor transplant where you have the ability to give bone marrow.

Yi-Bin Chen, MD: For the last couple of decades, the standard at Massachusetts General where I am, for a fully matched related, or unrelated donor, our standard graft versus host disease prevention platform is the combination of tacrolimus plus short course methotrexate after transplant. We use that for fully matched donors. For donors with any mismatch, be it a mismatched unrelated donor or a haploidentical donor, we would use a regimen that is built around high-dose post-transplant cyclophosphamide, or PTCy as we call it, in combination with tacrolimus and mycophenolate. Prior to ASH, that was our standard and has been for the last several years.

Corey Cutler, MD, MPH FRCPC: Hannah, is this any different at your center?

Hannah K. Choe, MD: No, it’s very similar.

Corey Cutler, MD, MPH FRCPC: New York is a little different, tell us about it.

Doris M. Ponce, MD: In New York, [Memorial] Sloan Kettering [Cancer Center] has invested many years, decades, studying T-cells ex-vivo, CD34 selection, T-cell depletion, and that’s part of the armamentaria for reduction of graft versus host disease. For this particular approach, it’s a CNI [calcineurin inhibitor]-free regimen, so patients are not exposed to CNI.

Corey Cutler, MD, MPH FRCPC: [TheASH meeting] has happened.

Yi-Bin Chen, MD: What’s the practice at Dana-Farber [Cancer Institute]?

Corey Cutler, MD, MPH FRCPC: The practice at our center is very similar to what you described, tacrolimus and methotrexate, 4 doses. In the mismatched setting, it’s either post-transplant cyclophosphamide, or abatacept.

Doris M. Ponce, MD: How do you use sirolimus in your regimen now?

Corey Cutler, MD, MPH FRCPC: We use sirolimus in our reduced-intensity transplants for the most part. We performed a randomized trial a number of years ago that suggested that outcomes might be a bit better. There are a number of centers that use sirolimus regularly, for example, [Fred] Hutch [Cancer Center], City of Hope, and the Moffitt Cancer Center are all regular users of sirolimus. Every now and then I will use sirolimus even in the myeloablative setting in someone who I don’t want to give methotrexate to, who I want to engraft a bit quicker, a day or two, or who has very high risk of getting bad mucositis.

Transcript edited for clarity.