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The Blood and Marrow Transplant Program at Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute has recently been named as a Blue Distinction Center for Transplantation of Adult Autologous and Allogeneic hematopoietic cells. Previously we had Steven M. Devine MD
only been awarded this distinction for recipients of Director, Blood and Marrow Transplant Program Ohio State University Comprehensive Cancer Center – Should you have a patient with medical coverage James Cancer Hospital and Solove Research Institute within the Blue Cross Network who may potentially benefit from an allogeneic cell transplant, they may New Trials Designed to Prevent
allogeneic transplantation is often a patient's best (and sometimes only) treatment option, efforts to Graft Versus Host Disease
reduce the risk of GVHD are of paramount impor- tance to investigators in the field. The Ohio State Despite overall improvements in the management University Blood and Marrow Transplant (BMT) of patients undergoing allogeneic blood or marrow Program is currently involved in a number of studies transplantation, acute graft versus host disease (GVHD) remains the major complication of this Our BMT Program has several ongoing or soon to procedure and after relapse of the primary disease, is be activated trials supported by The National the most common cause of mortality associated with Institutes of Health (NIH) designed in part to mitigate transplantation. The risk of GVHD is related to the GVHD. While most centers use pharmacological degree of matching between donor and recipient and agents like cyclosporine or tacrolimus to prevent is higher following unrelated donor compared to GVHD, T-cell depletion of the graft represents the sibling donor transplantation. The risk rises as the other end of the spectrum. This technique employs donor and recipient are less well matched. Since various physical or pharmacologic approaches to I N T H I S I S S U E ▼
New Trials Designed to Prevent Graft
OSU BMT and Myeloma Programs
Blood Marrow Drives
Versus Host Disease
Offer Several Clinical Trials for
Patients with Multiple Myeloma
Patient Profile
Blood and Marrow Stem Cell Transplant
Program Advanced Practice Nurses
Blood and Marrow Transplant Update S U M M E R / FA L L 2 0 0 7 New Trials Designed to Prevent Graft Versus Host Disease . . . continued on page 2)
remove the T-cells that cause GVHD from the graft very well matched volunteer donor. In OSU 06042, prior to transplantation. This is not a new approach we will attempt to identify donors mismatched at the but there are newer, more efficient methods now HLA-C locus in order to stimulate the donors natural available which are being evaluated. One of these killer (NK) cells to elicit a graft versus leukemia approaches is called positive selection. This approach response, according to the results generated by the uses immunoaffinity or immunomagnetic bead transplant group in Perugia, Italy and recently updated systems to separate the hematopoietic stem and in The Journal of Clinical Oncology (Aversa et al,).
progenitor cells from the cells comprising the innate This trial is being performed in collaboration with the BMT Programs at The University of Minnesota The approach most commonly taken uses immuno- (UMinn), Emory University, and the Moffitt Cancer magnetic beads containing antibodies to the CD34 Center and is funded by The National Cancer Institute antigen which is expressed on the stem/progenitor in conjunction with a Program Project Grant headed by cells but not the T-cells. The beads bind to the stem Dr. Jeffrey Miller at UMinn. Patients up to age 60 cells and are then passed through a magnetic field.
are eligible for this trial and are not required to be in The stem/progenitor cells expressing CD34 are retained within the magnetic field while the T/B, and At the other end of the spectrum, we are using NK cells are eluted away from them. This technique novel agents to prevent GVHD. Based on encouraging allows for a very efficient and relatively easy T-cell preliminary data generated by the BMT team at Dana depletion (up to 5 logs). A purified graft can then be Farber Cancer Institute in which the combination of transplanted into the recipient with little or no risk of tacrolimus and sirolimus (rapamycin) has been associated with very low risk of acute GVHD, BMT In BMT CTN 0303, we are using this technique in CTN 0402 is a phase III randomized clinical trial patients with acute myeloid leukemia (AML) in first or comparing the more standard approach using second remission. The patients receive a relatively tacrolimus and methotrexate to the combination of strong conditioning regimen containing chemotherapy tacrolimus and sirolimus. This trial is about to be and radiation but the patients do not have to be given opened at OSU as well as several BMT programs any post-transplant immunosuppressive drugs. Thus, throughout the United States. The trial is open to the risk of mucositis and other complications is dimin- patients with hematological malignancies undergoing ished with this approach. The patients must be myeloablative matched sibling donor transplantation.
between the ages of 18-60 years inclusive and have a If shown to be superior, the tacrolimus/sirolimus matched sibling donor available. This multi-center combination would represent the first change in trial is also open at The Memorial Sloan-Kettering and standard GVHD prophylaxis in over 15 years.
Dana Farber Cancer Centers, among others. The other The OSU BMT Program continues to expand its T-cell depletion trial we have open involves patients allogeneic transplant program primarily by combining with AML, myelodysplastic syndrome, and advanced excellent patient care with access to high quality chronic myelogeneous leukemia who are in need of an allogeneic transplant but who are unable to identify a New BMT Information on Jamesline.com
Jamesline.com has added a new section about The James' Blood and Marrow Transplant program.
Patients now have access to extensive information about The James' comprehensive BMT program including our patient care expertise, research and facilities.
You can access the new site by going to www.jamesline.com/go/bmt.
OSU BMT and Myeloma Programs
to move standard risk patients not eligible for a clinical trial on to autologous transplant followed by Offer Several Clinical Trials for
Patients with Multiple Myeloma
The Ohio State Multiple Myeloma
At Ohio State, we have two active Cancer and Clinical and Research Program
Leukemia Group B (CALGB) hematopoietic stem cell (www.jamesline.com/cancertypes/multiple_myeloma)
transplant protocols available for myeloma patients.
is led by Craig Hofmeister M.D. and Don Benson M.D.
The first is a phase III trial evaluating the survival Ph.D. In 2006, we performed 50 transplants for advantage of using lenalidomide (RevlimidÍ) mainte- myeloma and we see approximately 15 consultations per nance after autologous transplant in patients with stable month, most often in evaluation for hematopoietic stem or responsive disease to induction therapy. The second cell transplantation. OSU is an active member of CALGB is a phase II trial investigating the efficacy of autologous and the Multiple Myeloma Research Consortium transplant followed by non-ablative HLA-identical (MMRC). We have NCI/CTEP sponsored protocols with sibling transplant in patients with no more than one prior novel agents in myeloma as well as access to new drugs progression after induction therapy.
through the MMRC. We are focused on accruing We have also assembled an interesting array of patients to trials that ask interesting questions with clinical trials for patients with relapsed or refractory multiple myeloma. We have five trials open for accrual: 1) A phase I trial evaluating the monoclonal antibody We would like to work in partnership with you in the
1-7F9 that blocks the natural killer (NK) cell inhibitory management of patients with this difficult disease.
KIR pathway and potentially activates NK cell killing of If you would like to refer patients, please contact myeloma cells; 2) A phase I trial evaluating the inhibitor AVN-944 of the enzyme IMDPH involved in DNA (614-293-7433, Michelle.Johnson@osumc.edu)
synthesis that promotes apoptosis of rapidly dividing cells; 3) A phase I trial of the second generation proteasome inhibitor NPI-0052; 4) A phase I trial of (614-293-9165, Bryan.Craycraft@osumc.edu)
Flavopiridol, a novel RNA polymerase inhibitor with for non transplant referrals simply email demonstrated efficacy in Chronic Lymphocytic Leukemia (CLL); and 5) a dose-escalated phase I trial of (Craig.Hofmeister@osumc.edu)
lenalidomide (RevlimidÍ) combined with a novel mTOR Our partnership to support clinical trials that advance inhibitor CCI-779 - both agents have activity in myeloma the knowledge base in myeloma will ultimately prolong as single agents, preclinically the combination has synergistic activity, and this is one of the few steroid-free As this goes to press, data will be emerging from the Myeloma treatment sequence at Ohio State
American Society of Clinical Oncology 2007 meeting that less steroid exposure prolongs survival in Multiple Myeloma. Rajkumar et al. will present data showing an improved survival and fewer toxicities using upfront therapy with the combination of lenalidomide (RevlimidÍ)at 25 mg daily days 1-21 and low dose dexamethasone 40 mg weekly on days 1, 8, 15, 22 of a 28 day cycle compared to lenalidomide plus standard high dose dexamethasone on days 1-4, 9-12, 17-20. We have adopted this low dose dexamethasone strategy in our upfront therapy since Jan-2007 (see table 1) and prefer Blood and Marrow Transplant Update S U M M E R / FA L L 2 0 0 7 Off protocol upfront therapy for multiple myeloma
Risk stratification
Prioritized treatments
Velcade days 1,4,8,11 + 40 mg Decadron weekly q21 Revlimid 25 mg days 1-21 + 40 mg Decadron weekly q28 Revlimid 25 mg days 1-21 + 40 mg Decadron weekly q28 Autologous stem cell transplant candidates: Velcade days 1,4,8,11 + 40 mg Decadron weekly q21 Thalidomide 100 mg PO qHS continuous q42 days Thalidomide 100 mg PO qHS + 40 mg Decadron weekly q28 Myeloma clinical trials available at Ohio State
[NCI] Phase I trial of Lenalidomide and CCI-779 Eligibility:
2. Bilirubin < 1.5xULN, Creatinine < 2 mg/dL 3. Must have >25% increase in M-protein after last therapy 4. Exposure to prior lenalidomide or CCI-779 OK, not both [NCI] Phase I trial of Flavopiridol (RNA polymerase inhibitor) Eligibility:
4. Bilirubin < 2 xULN, Creatinine < 2 mg/dL Relapsed
[MMRC] Phase I of NPI-0052 (Proteasome inhibitor) refractory
Eligibility:
2. Hb > 8 g/dL, ANC > 1500, Platelets > 75K 3. Bilirubin < 1.5x ULN, Creatinine < 1.5xULN Phase I trial of AVN-944 (IMDPH inhibitor) Eligibility:
3. Bilirubin < 2 mg/dL, Creatinine < 2 mg/dL Eligibility:
1. At least 2 months since last chemotherapy 2. Ability of patient NK cells to bind anti-KIR 3. Bilirubin < 1.5x ULN, Creatinine < 2 mg/dL Plan to open in Jun-2007 [CALGB] Autologous alone or with Revlimid maintenance Eligibility:
1. Stable disease or responsive to 2+ mos. of any induction 2. No more than 12 mos. of any prior therapy, including Rev 3. No prior progression after initial therapy Transplant
[CALGB] Auto- then non-myeloablative sibling transplant Eligibility:
1. No more than 12 mos. alkylators, 18 mos. total treatment 2. No more than one prior progression after initial therapy Blood and Marrow Transplant Update S U M M E R / FA L L 2 0 0 7 PAT I E N T P R O F I L E : Joe Ogden
In 1996 Joe Ogden felt a lump in his groin and thought nothing of it, a short time later he received the diagnosis of Non-Hodgkin's Lymphoma. After two different rounds of chemo and two years of remission the Lymphoma returned. This time he needed a bone marrow transplant. His three sisters were not suitable matches and after two years of waiting, somewhat patiently, Joe found a donor from the National Marrow Donor Program. The transplant was successful, and then in April 2005 he discovered the cancer had once again returned this time on his vocal chord. After several more rounds of chemo, it was determined he would again need radiation and another bone marrow transplant. He received a second transplant from the same anonymous donor. Putting him in remission again and hopefully for good.
Through all of this Joe never lost his positive attitude or his faith in his medical team. He attributes his positive outlook to his family especially his grandson. Before cancer sidelined Joe he was an auctioneer, with his cancer in remission he felt it was time to give back to the medical community that had helped him. Putting his auctioneer skills to work in April 2006 he raised $10,000 for a bone marrow drive. So far the dollars he raised have registered 100 people to the National Marrow Donor Program. This fall he hopes to register at least 100 more. Joe has one more thing to look forward to, this summer he hopes to finally find out who his donor was. He thinks the least he should do is say thank you to the person that helped him not once but twice.
Blood and Marrow Stem Cell Transplant Program
The nurse practitioners work in both the inpatient and Advanced Practice Nurses
outpatient setting within the BMT program providing direct patient care to persons undergoing transplantation.
The Blood and Marrow Transplant (BMT) program is Each nurse practitioner collaborates with the physicians to comprised of a multidisplinary team which includes provide care to patients during the steps of pre-transplant physicians, advanced practice nurses, a nurse manager, evaluation, transplant process and post-transplant care.
a clinical nurse specialist, staff nurses, BMT patient Each nurse practitioner is assigned to a specific physician coordinators, research nurses, a pharmacist, a data outpatient clinic and is able to follow the clinic patient manager, social workers, patient care assistants, unit through the transplant process. Responsibilities of the clerical coordinators and many others. There are eight nurse practitioner include obtaining an initial history and advanced practice nurses known as nurse practitioners physical, daily patient assessments, ordering and reviewing who work with all of the members of the multidisciplinary results of diagnostic tests and laboratory data, writing team to provide care to persons undergoing a BMT.
prescriptions, assisting with the discharge planning In addition to BMT, many areas of clinical expertise are process, and ensuring the appropriate conduct of clinical represented among the nurse practitioners including research. The nurse practitioner also participates in cancer care, symptom management, hospice, critical care, ongoing patient and family education regarding the family practice, case management, and teaching.
transplant process, adverse effects and complications of transplant as well as symptom management.
The nurse practitioner collaborates with all members of the BMT health care team to assist with the facilitation of care through the transplant process. Patients may meet many of the nurse practitioners, but one nurse practitioner will be assigned to each patient to assist with continuity of care. The role of the nurse practitioner in BMT continues to evolve to assist in meeting the needs of persons undergoing transplantation.
Blood and Marrow Transplant Update S U M M E R / FA L L 2 0 0 7 Bone Marrow Drives
participation. Registration was held at the College of Medicine and the OSU Student Union. Children's Each year, more than 35, 000 children and adults in Hospital held 3 sites throughout the city. The drive was the United States develop life threatening diseases for a great success with a total of 569 new volunteer donors which a marrow or blood stem cell transplant could be joining the Registry. Of the 569 donors, 49 were of a a cure. Only 30 percent of patients in need of a stem cell transplant find a matched donor in their family.
In addition, the Blood and Marrow Transplantation The other 70 percent need to find an unrelated donor.
Program worked with the NMDP to hold it's own That means, every day, thousands of patients are Medical Center donor drive on September 29, 2006.
searching for a donor. The National Marrow Donor We are please to report a total of 168 employees joined Program® (NMDP) maintains a Registry of volunteer the Registry. We encourage everyone to consider donors that we can search. Over 6 million donors are becoming a donor in the NMDP. You could be the one registered with the NMDP and over 10 million donors are registered worldwide. Sadly, we still encounter Log onto MARROW.org for more information.
patients for whom we cannot find donors because they have less common tissue traits. The most difficult searches are for patients of minority races. Of the over 6 million donors in the Registry, only 1.6 million are of minority or mixed races. The need to promote minority The James, Ohio State University and Columbus Children's Hospital worked in collaboration with the NMDP to hold a bone marrow drive on November 2, 2006. The focus of the drive was to promote minority Ohio State’s Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute

Source: http://cancer.osu.edu/pdfs/BMT%20Update_Newsletter.pdf