Bone Marrow Transplant Update - Jan 2011
- Alternative donor program offers outstanding outcomes to unmatched donors
- Non-myeloablative regimens expand eligibility for older patients and those with co-morbidities
- Mini-transplant Plus Gleevec Improves Outcomes for Ph+ ALL Patients
Providing evidence-based care to cancer patients
Only 30 percent of transplant patients have matched sibling donors. Another 35 percent will find matched unrelated donors leaving the remaining 35 percent looking for alternatives. “For a long time, matched unrelated donors have been the alternative donors of choice,” says Dr. Paul O’Donnell. “Our outcomes using such donors consistently outperform other centers. Now we are able to offer those patients who can’t find a matched unrelated donor with the option of transplants using a haploidentical donor or unrelated cord blood.”
The transplant program using all three types of alternative donors is now well-developed with many protocols for full and mini-transplants. “Many centers across the country are finding that outcomes of transplants using haploidentical or cord blood donors are very similar to matched donors,” O’Donnell says. “The incidences of acute or chronic graft versus host disease are surprisingly less or similar to matched donors using current protocols.”
SCCA’s alternative donor program provides opportunities for virtually any patient to receive a transplant.
The key to success of a haploidentical transplant is the administration of high-dose cyclophosphamide after the transplant, “which is counter-intuitive,” according to O’Donnell. It’s given on days three and four post-transplant followed on day five with standard immunosuppressive treatments. “The cost of this drug is only about $300 – a wonderfully low-tech approach in our high-tech era,” he says.
SCCA physicians now routinely use a combination of two cord blood units to extend this type of donor option to adult patients, formerly restricted to pediatric patients. “New studies in which one of the cord blood units is grown-up in the lab pre-transplant have been successful in increasing the rate of engraftment post-transplant,” O’Donnell says.
SCCA’s Alternative Donor Program provides opportunities for virtually any patient to receive a transplant.
Examples of alternative donor protocols include:
Nonmyeloablative HCT for Hematologic Malignancies using Related, HLA-Haploidentical Donors (FHCRC-2372)
Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients with Hematologic Malignancies using Related, HLA-Haploidentical Donors: A Phase II trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source
Investigator: Paul O’Donnell, MD, PhD;
Conditions: Hematologic Malignancies;
I 131 Monoclonal Antibody BC8, Chemotherapy, TBI, and a Donor Bone Marrow Transplant for Advanced Acute Leukemia MDS (FHCRC-2186)
Hematopoietic Bone Marrow Transplantation for Patients with High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS) using Related HLA-Mismatched Donors: A Trial Using Radiolabeled Anti-CD45 Antibody Combined with Immunosuppression Before and After Transplantation
Investigator: John Pagel, MD, PhD;
Conditions: Leukemia, Myelodysplastic Syndromes;
Unrelated Donor Cord Blood Transplant w/Reduced-intensity Preparative Regimen (FHCRC-2239)
Transplantation of Unrelated Donor Umbilical Cord Blood in Patients with Hematological Malignancies Using a Reduced-intensity Preparative Regimen
Investigator: Colleen Delaney, MD, MSc;
Conditions: Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases;
Fludarabine, Cyclophosphamide + TBI Followed by Cord Blood SCT (FHCRC-2044)
A Pilot Study to Evaluate the Co-infusion of Ex Vivo Expanded Umbilical Cord Blood Progenitors with an Unmanipulated Cord Blood Graft in Patients Undergoing Umbilical Cord Blood Transplantation for Hematologic Malignancies
Investigator: Colleen Delaney, MD, MSc;
Conditions: Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes;
Read the full description of each trial and enroll your patients online at www.seattlecca.org/clinical-trials/transplant-list.cfm
Hematopoietic cell transplants that use non-myeloablative conditioning regimens are well tolerated by most patients who are ineligible for conventional high-dose conditioning prior to transplantation due to advanced age or co-morbidities.
Thanks to these “mini-transplants,” there is no absolute upper age limit for transplantation. Patients in their 60s, 70s, and 80s (as well as younger patients) now undergo non-myeloablative transplants at SCCA. The majority (60 percent) never have to be hospitalized during their transplant process and complete their conditioning, stem cell infusion, and recovery entirely in outpatient settings.
Mini-transplants, also called mixed chimeric transplants, “do not rely on high-dose cytotoxic therapy,” says Rainer Storb, MD, Head of the Transplantation Biology Program at Fred Hutchinson Cancer Research Center, “but rather rely on graft-versus-tumor effects for killing the patient’s cancer cells.” The low-dose conditioning regimen is administered to weaken the patient’s immune system so it accepts the donor’s stem cells.
Ideally, the transplanted cells engraft and a new immune system develops alongside the patient’s remaining immune system. For a time, the patient has two immune systems (mixed chimerism) before the patient’s original system eventually disappears.
Dr. George Georges is principal investigator for a promising transplant trial aimed at Ph+ ALL patients (Fludarabine + Radiation Followed by SCT for Leukemia; FHCRC-1581).
“In 1990, only about 10 percent or less of older patients with this disease survived long-term. Now, with imatinib given after allografting, we have a cohort of patients with 73 percent long-term disease-free survival,” Georges says.
Two weeks after nonmyeloablative transplant, patients begin taking imatinib or one of the other currently available tyrosine kinase inhibitors. Georges and his team have seen the best results in patients who receive their transplant while in first remission and who have no evidence of minimal residual disease at the time of transplant. Those with more advanced disease or who are in second remission do not do as well.
Ph+ ALL is a very lethal disease and older patients cannot tolerate a full myeloablative transplant. The mini-transplant allows for the opportunity for long-term survival, if it is followed-up with one to three years of imatinib treatment. Risks associated with the treatment are infections as a result of graft-versus-
For more information about this trial and whether your patient will qualify, please contact George Georges, MD at (206) 667-6886 or email@example.com.
Dr. Paul O’Donnell began his career studying chemistry and later earned graduate degrees in biochemistry and molecular biology. After a 20-year research scientist career at Memorial Sloan-Kettering Cancer Center in New York, where he studied retroviruses that cause leukemia in mice, O’Donnell felt the need to become more involved in the study of human diseases. He enrolled in Johns Hopkins School of Medicine where he later pursued a residency in internal medicine, an oncology fellowship, and then joined the faculty.
O’Donnell moved to Seattle to join the faculty of Fred Hutchinson Cancer Research Center in 2001. He became the medical director of the Inpatient Transplant Service which oversees about 45 attending physicians, 41 mid-level providers and oncology fellows. He is also working on leading-edge research using alternative donors for bone marrow transplantation at Fred Hutchinson Cancer Research Center.
Read more about Dr. O’Donnell at www.seattlecca.org/doctor/paul-v-odonnell.cfm
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