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He spoke about non-transplant therapies for Myelodysplasia (MDS). Azacytidine (5-Aza) produces hematological response in about 50% of MDS patients. It is being tested with sodium phenylbutyrate. R11577 works for some with AML but does not work in most cases of MDS. Arsenic Trioxide has also had some responses. The biology of MDS is not well understood. It is very heterogeneous. Azacytidine/decitabine are the most effective non-HSCT therapies.

The role of BMT in bone marrow failure: criteria and timing - H. Joachim Deeg;

In Aplastic Anemia, HSCT is superior to immmunosuppresive therapy for patients younger than 40 years old. After age 40 results are about the same. The best outcome for HSCT is seen in patients who have less than 20 transfusions and within one year of diagnosis.

At Fred Hutchinson there is little difference in long-term survival between MDS patients who receive stem cells from sibling donors and those transaplanted with stem cells from MUDs. Busulfan/Cytoxan seems to work better than TBI base regimens. PBSCT appears to work better than bone marrow transplantation, although this is not statistically significant. In low risk (IPSS scores of 2 or less) life expectancy is better when transplant is delayed until the disease progresses. High risk patients should go immediately to transplant.

NST has been used in older MDS patients with modest success. Fludarabine and TBI have been used as the preparative regimen.

Myelofibrosis patients who have a HBG of 10 or better and do not need transfusions have good outcomes with HSCT. Other patients have poorer outcomes.

New developments in both transplants and non-transplant therapies mean continuously reassessing optimal strategy.

New therapy in non-transplant management of bone marrow failure - Jeffrey Molldrem

Jeffrey Molldrem introduced Mia Hamm (the soccer player). They had just finished interviews to increase marrow donors. Mia's brother was diagnosed with Aplastic Anemia in 1997 and passed away from complications of a bone marrow transplant. There is more information on her web site: http://www.miafoundation.org/.

Immune Suppression has been used to treat cytopenias in MDS patients. ATG was given to transfusion dependent patients. In 61 patients with a median age of 61 and an IPSS score of 1 there was a response rate of 34% (a response in this case, meant that they were transfusion independent for 2 months). Survival was also better in the responding patients. This leads to the hypothesis that T-cells contribute to the cytopenias in at least some patients.

8:30 AM - 10:00 AM

PLENARY 2: Antigen Specific Function Following HSCT Session Chair: Robertson Parkman, MD;

Immune reconstitution after human HSCT - Robertson Parkman, MD;

Incidence of infections is about the same in patients undergoing URD transplant regardless of whether or not they have GVHD and is higher than the incidence in patients transplanted with stem cells from related donors. Patients who undergo PBSCT seem to be more resistant to infections. Adults have a decreased capacity to make new T-cells. This is even more true in older adults. Patients with URDs may have permanently impaired responses to certain bacteria.

Thymic epithelial function following HSCT - George Hollander, MD;

CLP to improve post-HSCT immunocompetence - Janice (Wes) Brown, MD

CLP stands for Common Lymphoid Progenitor cells. Treatment or prevention of CMV with ganciclovir has significant morbidity. CMV represents a considerable and recurrent burden to the immune system. CMV disease could be prevented with the transplantation of CMV specific T-cells. Progenitor cell transplantation may also be protective against aspergillus and other pathogens.

10:30 AM - 12:00 PM

CONCURRENT 4: Is Isolation Necessary after Stem Cell Transplantation? Session Chair: Alois Gratwohl, MD;

Can the goals of isolation still be achieved? - Alois Gratwohl, MD;

In the beginning of HSCT, isolation units (laminar air flow rooms) were routinely used. Sterile water and food were used as well as skin and gut decontamination. Patients enter the room before conditioning and left when they recovered. However there was no evidence that this benefited patients and isolation was too expensive.

In an EBMT study of more than 13,000 patients transplanted between 1980 and 2001, 61% of patients survived. 20% of the deaths were due to infection. The main improvement in surival since 1980 was reduced toxicity. Deaths due to viral infections have decreased but ARDS (Acute Respiratory Distress Syndrome) has increased. Epidemics of various organisms occur at different hospitals and are problematic. The incidence of epidemics is likely under-reported.

Outpatient care after allogeneic HSCT - James A Russell, MA, MB, FRCP;

288 patients with leukemia and MDS were transplanted in Calgary between 1988 and 1998. It appears that there are few infectious disease deaths that could be prevented by isolation . Most of the infections develop in patients after they leave the hospital. Older patients and patients with advanced disease have much higher 100 day mortality. There have been improvements in preventing early deaths in more recent years. Early death is still high in adults transplanted with stem cells from unrelated donors. However it seems that most can not be prevented by isolation.

Perhaps environment plays a role and different centers at different latitudes may have different incidences of infections. [There was a reference to a paper published about this, but I was unable to find a reference to this.]

Home care after allogeneic transplantation - Britt-Marie Svahn, RN;

In Sweden, patients were allowed to have an allogeneic transplant, almost entirely at home. Between 1998 and 2000, 60 patients were treated, 54 were given the choice of having the transplant at home or in the hospital. 36 patients choose to be at home. The majority of patients had an URD. No plants and pets were allowed in the home (they had to be removed if they were there). The infection control people from the hospital visited the home to make sure it was reasonably clean. All patients needed a caregiver. Patients were given chemo at the hospital. A nurse from the hospital visited each patient once or twice a day. The doctor talked with the patient by phone every day.

Outpatient allo HSCT is safe and there was no difference in infections. Patients were re-admitted if they had fever. Outpatients spent a median of 4 days in the hospital. There was no difference in fever or use of IV antibiotics. Home care patients used much less IV analgesics (in the discussion, it was said this was in part because home care patients did not want to be re-admitted, which does not sound like a good reason to use less pain medications) and used less IV nutrition. Acute GVHD was significantly less in home care group. There was 70% survival in the home care group which was better than the hospital group.

Again climate seems to be important and aspergillus incidence (and spore counts) are signficantly different in different latitudes. [Again no reference.]

Discussion - Olle Ringden, MD, PhD.

12:00 PM - 1:30 PM

Satellite Luncheon Symposium - Orphan Medical, Inc.
Transplantation for Infants to Young Adults: Expanding Our Options - Donna Wall, MD, Chair;
Supported by an educational grant from Orphan Medical, Inc.

This session focused on the difficulties of transplants in children, particularily in infants and adolescents.. The last part of the session focused on one particular problem, the dosing of busulfan in children.

Transplantation for adolescents/young adults: adults or children? - Ka Wah Chan;

There is no clear dividing line between children and adults. Different institutions treat some as adults and some as children. Although data on the outcome of HSCT in adolescents is not usually analyzed separately, data from the NMDP and IBMTR suggest treatment related mortality is higher in adolescents than in younger children. There are some differences in cancer incidence in adolescents and younger children. Most hereditary disorders are not seen in adolescents, since transplants for these patients are done at a young age.

There are significant psychological differences between adolescents and younger children. Adolescents are at a time in their life when they need to fit in. In addition, drug and alcohol abuse can be a problem in some patients.

Special issues in transplantation for infants - Martin Champagne;

Transplants done in infants (less than 1 year of age) are rare, and there are differences from older children. The most common indication for HSCT in infants are imuune deficiencies.

Haploidentical transplants have been done in infants with SCIDs (Severe Combined Immunodeficiency Diseases). Immune reconstitution make take 3-6 months and many patients require additional transplants.

Age and Busulfan dosing: optimizing the Busulfan-based regimen in children - Donna Wall;

There are many neurocognitive and endocrinologic long term problems with the use of TBI in children. For those reasons, there is a strong desire to avoid radiation if possible. IV Busulfan become available in 1999, and allows accurate dosing.

2:30 PM - 4:00 PM

IBMTR/ABMTR Chronic Leukemia Working Committee Meeting
Co-Chairs:IBMTR: Emilio Montserrat, MD-University of Barcelona; ABMTR: Sergio Giralt, MD-M.D. Anderson Cancer Center; Statistician: Kathleen Sobocinski, MS

Virtually no one is proposing HSCT early in any chronic phase CML patients. Gleevec should be tried first. Although there has been a substantial decrease in the number of HSCTs for CML there does not appear to an increase in the percentage of patients who are not in the chronic phase going to transplant.

The question is, if Gleevec is not curative, will its use negatively impact patients who then go on to transplant. 1. Is there a difference in transplant related mortality? 2. Is there a difference in the rates and severity of GVHD? 3. Is there a difference in relapse risk?

David Marks from Bristol, England proposed a study called: "The effect of smoking on transplant outcome." He wants to study CML patients since they are a relatively homogenous disease group and the risk factors in transplant patients are well understood. It is hypothesized that smokers will do worse. This study will not look at the risk of secondary tumors.

There was a a discussion on what the definition of a relapse is for CML patients. Molecular remission, which is the deepest form of remission for CML, means that there are no Philadelphia Chromosome (PH+) positive cells in about 100000 cells in 2 tests done with PCR 4 weeks apart (this was a definition given in the journal Blood, in an article which I do not have the reference to). Just because a patient is treated post-HSCT with a DLI or with Gleevec, does not necessarily mean that he or she has relapsed.

4:00 PM - 5:30 PM

WORKSHOP 2: Lung Injury after SCT: How Can We Improve Early Diagnosis and Treatment?
Co-Chairs: Kenneth R Cooke, MD, University of Michigan and Joan G Clarke, MD, Fred Hutchinson Cancer Research Center.

Diffuse lung injury is a major complication of HSCT. There is a 25-55% incidence with a mortality rate of 30-45% (these number seem to high to me). In about 50% of cases it is due to infection in the other cases, there is no infection.

Broncholitis Oblierans (BO) has no fever and has lung airway obstruction. It typically occurs more than 3 months post-HSCT.

Idiopathic Pnemonia Syndrome (IPS), has the symptoms of pneumonia with abnormal lung function with a median onset 2-3 months post-HSCT. It has a 50-80% mortality rate. Risk factors include transplants for diseases other then leukemia, GVHD and older age. T-cell depletion is associated with a lower incidence. Possible causes include toxic effects of conditioning, occult infection and immunologic mechanisms.

Is the lung a target organ of GVHD. IPS is associated with acute GVHD and BO is associated with chronic GVHD.

At the University of Michigan, IPS occurs in 5-20% of patients (higher incidence in patients with an URD) and has about a 75% mortality rate.

There is no standard therapy for IPS. Human Keratinocyte Growth Factor (KGF) prevents some alveolar cell destruction in mice. Another drug used for IPS is Enbrel. In a Phase I/II trial at the University of Michigan, which to date has enrolled 11 patients with IPS (and no infection), the use of Enbrel resulted in an 80% response rate (versus 32% in historical controls) and a mortality of 20% (versus the 75% sited above).

Broncholitis Oblierans (BO) is a nonspecific inflammatory injury of the small airways. It has an estimated incidence of 6-20%. Risk factors include GVHD. Symptoms are dry cough, dyspnea and wheezing. Diagnosis is via Pulmonary Function Test (PFT) and bronchoalveolar lavage to rule out infections. Treatment is immunosuppression for GVHD, although there is little data on efficacy.

At Fred Hutchinson, a large retrospective study found 1022 patients (who were alive and had a pre-treatment PFT) eligible for a study and 26% had airflow obstruction. Risk factors were GVHD and a history of respiratory disease in the first 100 days post-HSCT. There is significantly poorer survival in patients with airflow obstruction. There is anecdotal evidence in some patients that Extracorporeal photopheresis (ECP) seems to help.

5:45 PM - 8:45 PM

BMT Clinical Trials Network Fungal Prophylaxsis Protocol Investigators Meeting, Protocol #0101: A Randomized Double-blind Trial of Fluconazole versus Voriconazole for the Prevention of Invasive Fungal Infections in Allogeneic Blood and Marrow Transplant Recipients.

I was only able to attend part of this session (in order to make dinner). This is a trial to test whether prophylactic treatment with voriconizole is associated with fewer invasive fungal infections than the use of fluconazole. A secondary hypothesis is that early detection with the Galactamannan assay will reduce Invasive Fungal Infection mortality. The Galactmannan assay is a new blood test for aspergillus that is not yet FDA approved.

7:00 PM - 8:30 PM

Satellite Dinner Symposium - Schering AG Berlin,Germany/Berlex Oncology
Allogeneic Non-myeloablative SCT with Fludarabine-based Conditioning Regimens: the Treatment of the Future - Richard E Champlin, MD, chair, M.D. Anderson;
Supported by an educational grant from Schering AG Berlin, Germany/Berlex Oncology NST: where are we? - Robert Negrin, Stanford University;

Initial studies have shown donor engraftment and a graft versus tumor (GVT) effect with the use of NST. NST clearly reduces transplant related mortality and morbidity.

In Multiple Myeloma, a study treated patients initially with chemo (VAD) followed by an autologous PBSCT followed by an allogeneic NST. The NST was less toxic than the autologous PBSCT. The overall survival was 78% and progression free survival was 55% for patients who completed the entire treatment.

In CML in the first chronic phase studies have shown survival as high as 85% at 42 months post NST.

In a small study of NST for indolent Non-Hodgkin's Lymphoma, 17 of 20 patients survived. Long term remissions have been achieved.

The major remaining problem is disease progression and GVHD.

Overview of IwNST-sponsored core protocols - Sergio Giralt, M.D. Anderson Cancer Center;

There is a need for prospective studies in single diseases. GVHD continues to be a major problem. In refractory leukemia the results are particularly poor.

There have been no randomized trials comparing NST with full HSCT and there probably never will be. There have been no comparisons between different conditioning regimens.

The causes of death after NST are similar to after HSCT. There is a need to determine which regimens work best for which diseases.

The role of alemtuzumab in fludarabine-based conditioning regimens - Steve Mackinnon, University College London;

Campath (alemtuzumab) was added to the conditioning regimen in 93 patients with Non-Hodgkin's Lymphoma or CLL. 68 patients received PBSC from matched siblings, 25 received bone marrow from URDs. Patients were then given cyclosporine as GVHD prophylaxis. There was a low incidence of severe (grade III-IV) acute GVHD (4 patients) and chronic GVHD (5 patients). The actuarial 4 year overall survival was 35% for patients with high grade NHL and 69% in patients with low grade NHL.

The advantage of Campath was lower GVHD, because of in vivo T-cell depletion. The disadvantage was a high incidence of CMV disease. DLI was used in patients with mixed chimerism or after relapse.

NST for solid tumors - Richard Childs, National Heart, Lung and Blood Institute of the National Institutes of Health;

The use of NST with a conditioning regimen of fludarabine and cytoxan resulted in about a 40% response in patients with renal cell carcinoma. The response to treatment often takes many months, so it is important to not use NST in patients with rapidly progressing disease.

NST was used to treat patient with metastatic melanoma. It has produced disappointing results. At NIH 25 patients were treated and 4 patients responded. However responses were not durable and disease progression occurred 1-3 months afterwards. NST are no longer used at NIH to treat melanoma.

Saturday, February 1, 2003

6:45 AM - 8:15 AM

Satellite Breakfast Symposium - SuperGen, Inc.
Changing approaches to Acute and Chronic GvHD and Reduced-Intensity Allogeneic Bone Marrow Transplantation - Brenda Sandmaier, MD, chair; Fred Hutchinson Cancer Research Center.
Supported by an educational grant from SuperGen, Inc.
GvHD prophylaxis and treatment of GvHD - Daniel Couriel, M.D. Anderson Cancer Center, Houston, Texas;

Risk factors for severe chronic GVHD include more than 50% skin involvement, a platelet count of less than 100,000 and progressive onset (progressing from acute GVHD directly to chronic GVHD). There is no agreed upon definition of steroid refractory GVHD and no standard therapy for steroid refractory GVHD.

Infliximab has shown good responses, particularly in the gut but has only been studies in small trials. Rapamycin has also shown good responses, but also only in small trials. Extracorporeal photochemotherapy (ECP) has only shown responses, mainly in skin GVHD. Pentostatin at Johns Hopkins has had a 54% response. Once patients are steroid refractory, it is too late for effective therapy.

Treatment of chronic GVHD - Sherif Farag, Ohio State University, Columbus, Ohio;

Many therapies have been tried for steroid refractory chronic GVHD. These include thalidomide (which seems safe and effective, although some patients still discontinue its use because of side effects), cyclosporine, tacrolimus (FK-506 has good response, although significant renal toxicity) and Mycophenolate Mofetil (MMF).

Non-myeloablative stem cell transplantation - Gregory Bociek, University of Nebraska Medical Center, Omaha, Nebraska;

Pentostatin was used as part of the conditioning regimen along with a low dose (200 cGy) of total body irradiation. Pentostatin was given 21 day post transplant over 3 days.

Reduced intensity conditioning for allogeneic BMT - Francine Foss, New England Medical Center, Boston, Massachusetts;

92 patients were treated with non-myeloablative stem cell transplants with a preparative regimen consisting of extracorporeal photochemotherapy, pentostatin and 600 cGy of TBI. GVHD was relatively low, only 17% had grade II-IV acute GVHD and only 12% had extensive chronic GVHD. 5 patients failed to engraft, all of who had refractory AML that was not in remission at the time of transplant. There was a 1 year survival rate of about 60% and about a 25% relapse rate. In AML patients 8/20 relapsed (if the 20 included the 5 who did not engraft, then overall survival for AML patients looks poor).

8:30 AM - 10:00 AM

PLENARY 3: Novel Regimens for Autologous Transplantation, Session Chair: Julie Vose, MD

Novel transplantation regimens for NHL: vaccines, radioimmunotherapy, monoclonal antibodies - Julie Vose, MD, University of Nebraska;

Rituxan, a monoclonal antibody has been used in relapsed Non-Hodgkin's Lymphoma (NHL). It can be used for in vivo purging, prior to a stem cell harvest. Its use appears to improve survival compared to historical controls.

Concerns about Rituxan are that some studies show an unexplained neutropenia after Rituxan is given post-HSCT. Some studies have also shown increased lung complications. It may only be effecting in patients who are BCL-2 positive.

A monoclonal antibody attached to a radioactive particle is a radioimmuno conjugate, for example Bexxar. At Fred Hutchinson Bexxar has been used instead of TBI with the same chemotherapy drugs as a preparative regimen for an autologous HSCT and shows better survival compared to historical controls. Other places are combining Bexxar with other drugs. At Nebraska they are using low dose Bexxar with BEAM, City of Hope is adding Zevalin (to Bexxar and perhaps something else). At Stanford a vaccine is used after autologous HSCT, in a small study 5/12 patients relapsed.

The addition or monoclonal antibodies to transplant regimens for NHL appears to improve the efficacy, but there needs to be a randomized trial.

Update on autologous transplant regimens for AML - Richard Jones, MD,PhD, Johns Hopkins;

Most doctors assume that all autologous HSCT regimens for AML are about the same and most relapse are from systemic disease and/or leukemia cells that remain in the graft. There is a need for a novel post transplant therapy that mimics the allogeneic GVL effect. It must target the leukemic stem cell. There is an ongoing multi-center trial using an autologous HSCT with a vaccine. Leukemia cells are harvested at diagnosis to make the vaccine.

Transplant regimens using cellular therapy for hematologic malignancies - Robert Negrin, MD, Stanford University;

10:45 AM - 11:45 AM

E. Donnall Thomas Lecture: "Apoptosis: 'Tis Death That Makes Life Live" Dr. Tak Mak, molecular biologist credited with first describing T-cell receptors and how the receptors recognize and defeat invading viruses, bacteria and oncogenes, will present the annual E. Donnell Thomas lecture.

Tak Mak described the cellular mechanisms of apoptosis (programmed cell death). Apoptosis is required during fetal development. Tumor cells mutate genes to both suppress apoptosis and promote proliferation.

MALT (Mucosa-Associated Lymphoid Tissue) lymphoma develops at sites of chronic infections. H. Pylori is associated with almost all cases. Early MALT is dependent on H. Pylori and can usually be cured with antibiotics. However late MALT has the p53 gene inactivated and p16 deletion and can not typically be cured with antibiotics alone.

12:00 PM - 1:30 PM

Satellite Luncheon Symposium - Pfizer Inc.
Fungal Infections Following BMT: Re-examining Current Approaches - John R. Wingard, MD, Chair;
Supported by an educational grant from Pfizer Inc.

Changing times: patient characteristics and fungal epidemiology - John R. Wingard, University of Florida College of Medicine;

There are two peaks of fungal infections. Candida peaks about 20 days post transplant, although anti-fungal prophylaxis has reduced this significantly. The second peak is around day +100 and is mostly aspergillus. Worldwide there is an incidence Invasive Aspergillosis of about 15%. The rate of Invasive Fungal Infections (IFI) in patients with stage III-IV GVHD is about 35%.

Moving on to new antifungal agents for invasive aspergillosis - Thomas F. Patterson, University of Texas Health Science Center at San Antonio;

New therapies and diagnostic tools are needed to improve the prognosis of patients with IFI. Newer drugs include Amphotericin B Lipid formulations.

A new class of drugs in the Echinocandins. This include Caspofungin (MK-0991), Micafungin (FK463) and Andiulfungin (VER-002). They break down the cell wall of fungus but not human cells. Casponfungin has shown a better response rate (41%) compared to historical controls (17%) in high risk patients, 67% had hematological malignancies.

The Azoles also have activity. Posaconazole is a new drug that is in Phase 2/3 studies. Voriconazole is approved and can be given orally or IV.

Diagnosis of invasive aspergillosis: making it earlier - John R. Wingard;

Aspergillus and other molds have a rising incidence and represent the main infectious therat after allogeneic HSCT. New treatment options are becoming available and are needed. Early detection should lead to better results.

4:00 PM - 5:00 PM

ORAL ABSTRACT PRESENTATIONS: Session 3
Four oral presentations selected from Submitted abstracts on Histocompatibility/Alternative Stem Cell Sources and Graft Processing, Moderated by Mitchell S. Cairo.

The abstracts were published in Biology of Blood and Marrow Transplantation, February, 2003, Volume 9, Number 2.

Interleukin-10 and tumour necrosis factor alpha haplotypes predict transplant related mortality after unrelated donor stem cell transplants, Hows J. M., Division of Transplantation Sciences, Department of Clinical Medicine, University of Bristol, Bristol, United Kingdom.

Maturation stage of cord blood natural killer cells, Duval M, et. al. Division of Hemato-Oncology, Hopital Sainte-Justine, Montreal, QC, Canada, Montreal, QC, Canada.

High incidence of Epstein-Barr virus lymphoproliferative disease (EBV-LPD) after CD34-selected autologous peripheral blood stem cell transplant (PBSCT) in children with neuroblastoma(NB), Grupp S., N. J. Childrens Hospital, Philadelphia, PA;

EBV-LPD is rate in autologous HSCT. Risk factors for the development of EBV-LPD in allogeneic HSCT are T-cell depletion, GVHD and larger doses of immunosuppressive drugs.

Previous studies have shown that increasing the dose intensity of chemotherapy improves Event Free Survival (EFS) in neuroblastoma patients.

415 patients with neuroblastoma were treated with tandem PBSCTs. CD34 selection was used on the stem cells in an attempt to remove tumor cells. 5 patients developed EBV-LPD, they were treated and the EBV-LPD did not reoccur. Neuroblastoma patients treated with tandem CD34 selected PBSCT may be at a higher risk of developing EBV-LPD and screening for the Epstein-Barr virus (EBV) is recommended.

Optimal use of peripheral CD34 counts (PCD34) to guide leukapheresis in autologous peripheral hematopoietic stem cell transplantation (PHSCT), Griffin D. L, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.

Sunday, February 2, 2003

6:45 AM - 8:15 AM

Satellite Breakfast Symposium
Novel Applications of Photoimmunotherapy in the Management of GvHD - Francine Foss, MD, New England Medical Center, chair;
Supported by an educational grant from THERAKOS, a Johnson & Johnson Company

Extracorporeal photochemotherapy (ECP), also called Extracorporeal photopheresis) involves removing cells from the peripheral blood, exposing them to 8-MOP which make them more sensitive to ultraviolet light. The cells are then irradiated and returned to the patient.

Photopheresis in the prevention of GvHD - Francine Foss;

ECP has been used in the treatment of chronic GVHD at NEMC. 24 patients have been treated and 70% responded to ECP. All had extensive steroid refractory chronic GVHD.

ECP, given at day -7 and -6 as part of the preparative regimen for NST. It is given with Pentostatin (days -5 and -4) and a medium dose of TBI (in 3 fractions on day -3 and -2). This appears to be largely the same group as reported on in the Saturday Breakfast Symposium, although the number reported here seemed to be somewhat different.

Extracorporeal photopheresis for the management of cutaneous GvHD - Paolo Anderlini, M.D. Anderson Cancer Center, Houston, Texas;

A retrospective analysis of all patients who received ECP for the treatment of cutaneous chronic GVHD between September, 1998 and December, 2000 at M.D. Anderson. Only patients who were treated after day 100 and received at least 4 weeks of ECP are included in this analysis. There were 32 patients with a median age of 43. 30 of the patients had received other therapies for chronic GVHD before ECP. The complete response rate was 25% and the partial response rate was 34%. 63% of patients had a steroid sparing response (which means there was at least a 50% reduction in amount of steroids required). However 11 of the patients died, all the deaths were due to chronic GVHD or related infections. Of the 20 patients who survive (one was lost to followup), all but one remain on some immunosuppressive therapy for chronic GVHD.

Conclusion: ECP can be given over an extended period of time and has a substantial response rate in cutaneous chronic GVHD.

Extracorporeal photochemotherapy for pediatric patients with acute and chronic GvHD - Roberto Dall'Amico, University of Padua School of Medicine, Padua, Italy;

Another retrospective report on the use of ECP, this time in children. 4 centers in Italy treated 77 patients with ECP, from January, 1992 to December, 2000. There were 33 patients treated for acute GVHD, with complete regression of skin, liver and gut symptoms in 71%, 57% and 63% of patients respectively. 44 patients with chronic GVHD were treated with ECP for 6 months. 15 (44%) had a complete response and 10 (29.5%) had a partial response.

Conclusion: ECP is a non-aggressive treatment with mild side-effects that may benefit pediatric patients with both acute and chronic GVHD who do not respond to standard therapy.

8:30 AM - 10:00 AM

PLENARY 4: Homing Session Chair: Richard O'Reilly, MD;

Homing of blood-born cells to the bone marrow - Irina Mazo, MD, PhD, Harvard University;

Chemokines and Leukocyte Homing - Campbell, Stanford University;

Lymphocytes are in constant circulation looking for antigens. Granolyctes leave the blood stream and go to sites of inflammation. Lymphocytes are mainly in lymph nodes. Chemokines are responsible help mediate the different functions of these different kinds of leukocytes.

Chemokines and chemokine receptors in organ-selective metastasis of cancer - Sam T Hwang, MD, PhD;

There are two main ways for metastatis to occur, through the lymph nodes and through the blood stream. The CCR7 chemokine helps dendritic cells to migrate to lymph nodes, which is useful for an immune response, but it also helps melanoma cells to metstasize.

10:30 AM - 12:00 PM

CONCURRENT 6: Transplant Center Resources - What Do We Need to Give High-Quality Care? Session Chair: J Douglas Rizzo, MD

IBMTR/ABMTR survey of US transplant centers - Fausto R.Loberiza Jr., MD, MS;

This survey looked at practices at many different centers that are part of the IBMTR/ABMTR.

Follow-up, about 75% of centers follow allogeneic patients every month from 3 months to 1 year post HSCT. Most follow autologous patients every 3 months. After 1 year most follow allogeneic patients every month, while autologous patients are followed every 6 months.

Most center do allogeneic HSCTs. The median number of transplants done in a year is 32, with 19 allogeneic transplants and 13 autologous.

Most centers have a 1:2 or 1:3 nurse to patient ratio.

The median number of beds in each center is 8. Most centers used HEPA filtering. 70% are in Centers of Excellence, 50% are FACT accredited, with another 30% having applied for accreditation. FACT accreditation seems to show a survival advantage - this may be because major centers are getting FACT accreditation first and it may be that major centers with more experience do better and that FACT accreditation has little to do with survival.

In the future they will look at 100 day and 1 year transplant related mortality.

Canadian analysis of required resources for transplant centers - Eric J Bow, MD;

Until recently patients in Manitoba were sent to other provinces (or the U.S.) if they needed a transplant. A program has now been establiched in Manitoba.

European perspective on transplant center resources - Jane Apperly, MBChB;

This is based on data reported to the European Bone Marrow Transplant Registry (EBMT).

There is a clear correlation between GNP and transplants rates in different countries. There is also a correlation between per capita health care expenditures and transplant rates.

They looked at whether the number of transplants done at a center effected outcome. Looking at PBSCT for CML, teams with more experience had less transplant related mortalitity (TRM) than teams with less experience. However this difference did not show up when bone marrow was used. Teams that did more URD transplants had less TRM.

Insurance industry perspective: what determines excellence? - Richard Watt, MD.

12:30 PM - 2:00 PM

IBMTR/ABMTR Late Effects Working Committee Meeting Chair:Gerard Socie,MD,PhD-Hopital Saint-Louis; Statisticians: Kathleen A. Sobocinski, MS and J. Douglas Rizzo, MD.

Although I recall this being an interesting session, I did not take any notes.

2:30 PM - 4:00 PM

IBMTR/ABMTR Acute Leukemia Working Committee Meeting
Co-Chairs: AML: Armand Keating,MD - Princess Margaret Hospital; ALL: Daniel J. Weisdorf,MD - University of Minnesota; Statistician: Waleska Perez, MPH.

The agenda and studies discussed at this meeting are available online (You will need the Adobe® Acrobat® Reader™).

LK01-01 is an attempt to develop a decision procedure to decide on whether to transplant patients with MDS. Patients with less aggressive disease (an IPSS score of no more than 2) do better when transplant is delayed for several years. Patients with more aggressive disease (IPSS at least 2) should get a transplant immediately.

Another study is looking at whether the outcome of transplants (for both acute and chronic leukemia) in different among different ethnic groups. So far, the data seems to show that Hispanics seem to have a higher probability of relapse, with a lower risk of chronic GVHD and poorer disease free survival. Other groups (Blacks, Caucasians, Asians) have similar outcomes. However there is no socio-economic data available to see if that is a factor.

4:00 PM - 5:30 PM

WORKSHOP 4: PBSC from Unrelated Donors: Can We Exploit Them to Improve Outcome?
Co-Chairs: Claudio Anasetti, MD and Dennis Confer, MD.

See also Transplanting From Alternative Donor Sources: Enhancing Outcomes, John R. Wingard, MD., from Medscape.

In matched sibling transplants, overall survival is similar when bone marrow (BM) or peripheral blood (PB) is used. There seems to be a little more relapses with BM and better survival in high risk patients with PB.

A French study showed more chronic GVHD in patients receiving PB as well as more extensive GVHD. There was no difference in survival. Patients who received a lower dose of CD34 cells did better.

In a Seattle study using URD in non-myeloablative transplants (using a conditioning regimen of 200 cGy of TBI and Fludarbine), patients who received BM had about a 50% rejection rate, while 85% of patients receiving PB engrafted. Patients receiving PB had a higher survival rate. Patients who had less than 5% blasts (presumably in patients with AML/MDS) also did better. In another study in Seattle with fully myeloablative conditioning, using BM with a higher CD34 count correlated with better survival. Using PB from URD patients with either a high dose or a low dose of CD34 cells had poorer survival. It seems that CD34 dose is important, but it must not be too high or too low.

A randomized trial of PB versus BM in patients being transplanted with URD donors was conducted in Sweden. There were 107 pateints in each group. Patients who received PB engrafted more quickly. The rates of severe (stage II-IV) GVHD was similar in both groups and the rates of chronic GVHD did not differ. The transplant related mortality (TRM) and the relapse free survival (RFS) were similar in both groups.

At Dana Farber, a study using CD8+ (as I recall, they were selecting mostly cells that expressed the CD8 antigen) T-cell depletion enrolled 25 patients and non-myeloablative conditioning. All patients engrafted. After 3-6 months there was 100% donor chimerism. There was 1 relapse and 4 transplant related deaths. 20 patients are alive and disease free, although there has been less than 1 year of followup.

7:00 PM - 8:30 PM

Satellite Dinner Symposium - GlaxoSmithKline, Inc.
Advances in the Diagnosis and Management of PCP and Other Opportunistic Infections Following SCT - Thomas R Spitzer, MD, Chair;
Supported by an educational grant from GlaxoSmithKline, Inc.

See also Combating Infections in HSCT Recipients, by W. Garrett Nichols, MD, MEpi, from Medscape.

Overview: Treatment settings and duration of risk - Richard Nash, Fred Hutchinson Cancer Research Center, Seattle, Washington;

Current treatment strategies - Michael Boeckh, Fred Hutchinson Cancer Research Center, Seattle, Washington;

The incidence of PCP was reduced markedly when prophylaxis was added (in 1977 at Fred Hutchinson). First line therapy is intermittent TMP-SMX (2 days/week). However a significant number (about 30%) of patients do not tolerate it well and require other agents. Second line treatments are not standard. Dapsone has good efficacy but its toxicity is not well known. Other drugs have been used, but there is little data on efficacy and toxicity.

New strategies for the prevention of PCP and other opportunistic infections following SCT - Thomas R. Spitzer, Massachusetts General Hospital, Boston, Massachusetts;

Multiple prophylaxis strategies are required for PCP and other opportunistic infections. The choice of regimens should be based on institutional infection data and patient characteristics. Controlled trials to determine the best strategies are important.

Monday, February 3, 2003

6:45 AM - 8:15 AM

Satellite Breakfast Symposium - Baxter Oncology
Reconstructing Immunity Following Allogeneic Transplantation - Edmund K. Waller, MD, PhD, Emory University, Chair;
Supported by an educational grant from Baxter Oncology

These breakfasts are very early, plus I had to pack, so I missed the introduction and the beginning of Ted Waller's talk.

Tabula Rosa: Re-writing the immune system after allogeneic transplantation - Edmund K. Waller;

In T-cell depleted haploidentical transplant (e.g. from a parent), T-cell recovery is poor and takes a long time. The majority of deaths come from infection. Only in younger patients (up to about age 20) is there reasonable T-cell recovery. In mice, adding memory T-cells appears to increase T-cell recovery without increasing the risk of GVHD.

A new method for isolating tumor-specific CD8+ lymphocytes - Oystein Amellem, Dynal Biotech ASA;

Described a new method of isolating CD8+ lymphocytes using a device made at Dynal Biotech.

Adoptive transfer of IL10 anergized T-cells to haploidentical recipients - Maria-Grazia Roncarolo;

The idea is to do a Peripheral Blood harvest and select CD34+ cells to produce engraftment. At 30 days or so post transplant, T-cells that are anergized with IL-10 are re-infused. T-cells anergized with IL-10 should not cause GVHD but should provide protection against infection. A pilot clinical trial of this approach has been started, with a dose-escalating protocol (larger doses of anergized T-cells are given to patients enrolled later). In patients treated so far, only a low dose of anergized T-cells have been reinfused and there has been little effect on T-cell reconstitution, only 1 patient had some additional immune reconstitution.

8:30 AM - 10:00 AM

CONCURRENT 9: International Session: Non-Myeloablative Transplantation
Session Co-Chairs: Jane Apperly and Alexandra Filipovich;

Introduction and development - Alois Gratwohl;

The tools of HSCT are:

  1. Tumor load reduction and immune suppression
  2. Graft versus leukemia (GVL)

In the EBMT registry, about 27% of allogeneic HSCT in Europe were NST in 2001. Should these be compared to standard HSCT or to chemotherapy. Increased acute GVHD leads to poorer survival in CML patients and limited chronic GVHD leads to improved survival. The challenge is to define the role of NST versus fully myeloablative HSCT.

Current EBMT experience in NST for CML - Charles Crawley;

Most series have reported less than 10 patients with CML. Or et. al., ( Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase, Reuven Or, Michael Y. Shapira, Igor Resnick, Avraham Amar, Aliza Ackerstein, Simcha Samuel, Memet Aker, Elizabeth Naparstek, Arnon Nagler, and Shimon Slavin, Blood, Volume 101, Number 2, page 441) describe NST in 24 patients. There were no transplanted related deaths by day 100 and only 3 deaths overall. The Disease Free Survival was 85% at 5 years.

Uzunel, et. al. ( Kinetics of minimal residual disease and chimerism in patients with chronic myeloid leukemia after nonmyeloablative conditioning and allogeneic stem cell transplantation, Mehmet Uzunel, Jonas Mattsson, Mats Brune, Jan-Erik Johansson, Johan Aschan, and Olle Ringdn) treated 15 patients with a median age of 50. 13/15 were alive at a median of 20 months post transplant.

Overall there are 223 patients in the EBMT database how have had a NST for CML. The median age is 50. 60% of had CML in the first chronic phase. 148 (67%) had a matched sibling donr. The median time from diagnosis to transplant was 15 months. 80% of the patients had a NST for their first transplant. There were 22 different chemotherapy regimens used. 67% were transplanted with PBSC with the rest transplanted with bone marrow. Full donor chimerism was achieved in 70% of patients and at least 95% donor chimerism in 75% of patients.

Only 8% of those patients had chronic GVHD of grade III or IV with 26% having extensive chronic GVHD. The transplant related mortality was 24%, it was higher in patients with advanced disease.

The overall 2 year survival (OS) was 54%, with progression free survival (PFS) of 38%. For patients transplanted in the first chronic phase, OS was 67%. 48 of 157 patients had a DLI, most of them for relapse (I am not sure why only 157 patients were considered here). 23 of 128 patients received Gleevec, most for relapse.

Conclusion: NST is feasible in older patients. The disease phase at transplant is the most important predicator of survival.

Current experience in NST for multiple myeloma - Christopher Bredeson;

Multiple Myeloma (MM) responses to DLI, In one series of 98 patients, 36% achieved a complete remission and 22% a partial remission after a DLI. However 52% had acute GVHD and 36% had chronic GVHD. Conclusion, there is a graft versus myeloma effect.

In Seattle, 54 patients were treated with an autologous transplant followed by an allo NST. Most patient were not at high risk as they had responded to previous therapy. There was an 80% overall survival at a median of 18 months post allogeneic NST. The rate of chronic GVHD was 46%.

It seems that for MM, patients are getting NST instead of fully myeloablative HSCT, but the patient characteristics are the same (i.e. the patients getting NST are not older than the patients getting a full HSCT).

Summary and Perspective - Alexandra Filipovich

10:30 AM - 12:00 PM

WORKSHOP 7: Clinical Puzzles: How Can Registry Studies Help Answer Them?
Co-Chairs: Daniel Weisdorf, MD and Olle Ringden, MD, PhD

This session was an showed how the registries (IBMTR, ABMTR, EBMT) can be used to study interesting questions. Several puzzles were used to illustrate this.

Martin Tallman talked about whether consolidation chemotherapy should be given to patients with AML in first complete remission who were going to go on to an allogeneic transplant. At the time of the study there was no consensus on this issue. The study looked at registry data and found no different in Leukemia Free Survival or Overall Survival in patients going directly to a transplant following induction chemotherapy versus patients who first had standard dose or high dose chemotherapy. [AML patients are typically treated with induction chemotherapy to get them into remission. After they obtain remission, there are 2 basic options, more chemotherapy called consolidation or some kind of HSCT. Standard chemotherapy now is high dose chemotherapy, although lower doses have been used in the past, this is what is referred to as "standard dose" above.]

Hilliard Lazarus looked at what the optimal therapy is for AML if there is no sibling donor, comparing the results of autologous transplant versus transplants using URD. The gold standard to answer this question would be a randomized trial, but that would be extremely difficult and will never be done. Outcomes were compared for patients receiving autologous transplants versus those receiving transplants using URD. There were 684 autologous transplants in the ABMTR versus 515 patients who received transplanted from URD in the NMDP database, between the years of 1989 and 1996. The transplant related mortality was 50% for those in second complete remission who received a transplant from an URD and 40% for those in first complete remission. The Overall Survival was better in autologous HSCT.

10:30 AM - 12:00 PM

WORKSHOP 9: Terrorism: Is the Transplant Community Prepared? Chair: Dennis Confer, MD, NMDP

This looked to be an interesting session that I only caught the tail end of. You might be wondering what terrorism has to do with blood and marrow transplants. If there were an isolated nuclear bomb attack or a so-called "dirty" bomb, there might be quite a few people who would need a transplant. NMDP is developing a contingency plan to provide donors in case of such an attack.



I would like to thank the National Marrow Donor Program (NMDP) and the Bone Marrow Transplantation Branch of the Department of Transplantation of the Office of Special Programs of the United States Department of Health Resources and Services Administration (HRSA) for paying for my travel and conference registration. The views expressed in this article are my own and do not necessarily reflect the views of NMDP or HRSA. Also I would like to thank Sue Stewart of the BMT Infonet for her helpful comments.

Art Flatau flataua@acm.org

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