Clinical Scenario: A 38-Year-Old Man with Ph+ ALL

Transcript:

Bonnie J. Dirr, APRN:Good day, and welcome to OncLive: Inside the Clinic. Today’s program is entitled “A Team Based Approach to the Management of Graft-vs-Host Disease.” I am Bonnie Dirr. I’m a nurse practitioner at the Dana-Farber Cancer Institute here in Boston, Massachusetts. I will be your moderator for today’s program. I’m joined by my institutional colleagues, Dr Mahasweta Gooptu and Dr Eno Inyang. They both will serve as our panelists today. I would like to take a moment to have them introduce themselves. Dr Gooptu, I’d like to start with you, please.

Mahasweta Gooptu, MD: My name is Mahasweta Gooptu. I am one of the attending physicians in adult stem cell transplantation at Dana-Farber Cancer Institute. I am an assistant professor at the Harvard Medical School. In this capacity, I work with Bonnie, my nurse practitioner, and Dr Inyang, our pharmacist, on a daily basis, and I’m looking forward to presenting this team-based approach to you.

Bonnie J. Dirr, APRN:Thank you. Dr Inyang, welcome. Would it be possible for you to tell us a little bit about yourself?

Eno-Abasi Inyang, PharmD, BCPS, BCOP: Certainly. My name is Eno Inyang. I am a stem cell transplant clinical pharmacy specialist and serve as a director of our oncology residency program for our pharmacists at Dana-Farber Cancer Institute. On the side, I also work as a clinical pharmacy manager for Dana-Farber [Clinical Institute], working with our education and professional development program. I’m really excited to be here today and joined by Bonnie and Dr Gooptu, who I worked closely with, with managing our patients in the clinic.

Bonnie J. Dirr, APRN: Thank you to both Dr Gooptu and Dr Inyang for joining us today. Today, we are going to discuss and assess the treatment of stem cell transplant patients, particularly focusing on graft-vs-host disease [GVHD]. We will be presenting an actual case scenario and discuss the management both before and after transplant to demonstrate how our data guide our practice. Let’s get started. CB is a 38-year-old male with a history of Ph+ ALL [Philadelphia chromosome-positive acute lymphoblastic leukemia] who presented for a stem cell transplant with cyclophosphamide in TBI [total body irradiation]. It was a matched related stem cell transplant, on a treatment plan 764 with tacrolimus and methotrexate as his GVHD prophylaxis. His past medical history at the time of his stem cell transplant was Ph+ ALL as well as obesity. Dr Gooptu, could you please share with us a few points to set the stage for CB, briefly explaining to us the indications for stem cell transplant with a malignancy such as ALL, the donor types that were available to select, and what conditioning regimens were used as part of this allogeneic stem cell transplantation.

Mahasweta Gooptu, MD: CB was diagnosed with Ph+ ALL, denoting Philadelphia chromosome-positive ALL. In this disease, I would say even up to 5 years ago, all patients with Ph+ ALL would come to transplant, preferably in first complete remission with minimal residual disease negativity. There has been a little bit of an evolution and thought in this space, and now we really focus more on the high-risk Ph+ ALL patients who have certain mutations like the IKAROS (IKZF1 gene) mutation or do not achieve a deep molecular remission, so CB was in that category. He did require an allogeneic transplant as a curative strategy. In terms of donor types, in the algorithm that we follow at the Dana-Farber Cancer Institute, which mirrors the best available data and best practices, we look at matched sibling donors first, if we are fortunate enough to get them, because the best transplant outcomes are achieved with matched sibling donors. When matched sibling donor is not available, then our next go-to is a matched unrelated donor who would be what we call a full match, which would be an 8 out of 8 match for the National Marrow Donor Program because once again, those donors have better outcomes than donors with any degree of mismatch.

If we don’t get a fully matched unrelated donor, then we may consider using haploidentical donors who are typically family members, either a sibling or a child, or even a parent in some cases who are 50% matched to the patient, and also probably equivalent [to that] would be mismatched donors from the unrelated donor registry, particularly single-antigen mismatch donors. In terms of conditioning, ALL is the one disease where we use total body irradiation as part of the conditioning regimen, along with another chemotherapeutic agent which could be cyclophosphamide or fludarabine. And we do this because of the data that show that the deepest remission rates and reduction of relapse is achieved by using a TBI-based regimen extrapolated a lot from the pediatric literature. So, with CB we were fortunate enough that he had a related sibling donor who was willing to be his donor, and we used total body irradiation along with cyclophosphamide. Acknowledging that this happened perhaps 4 or 5 years ago, we used tacrolimus and methotrexate because posttransplant cyclophosphamide had not yet really made inroads into the HLA [human leukocyte antigens] match setting at the time. Methotrexate was [a rather] standard prophylaxis at the time. Just a brief note that we would have used bone marrow product if we could have. But his sibling, for various reasons, which we can’t disclose here, could only donate peripheral blood stem cells, and this will have a bearing on our discussion on GVHD.

Bonnie J. Dirr, APRN: Thank you, Dr Gooptu.

Transcript edited for clarity.