ALBERT

Description: Advances in supportive care have reduced early treatment related mortality with ASCT to approximately 1%. Registry data has shown that relapse is the cause of treatment failure in approximately 80% of patients. However, non-relapse mortality (NRM), over time, affects 20% of transplant recipients. Delayed NRM is poorly studied. To characterize the factors associated with NRM, we reviewed 1573 consecutive autologous transplants performed at the Cleveland Clinic from 1/1992 through 12/2005. This analysis included only adult patients (pts) receiving peripheral stem cells, busulfan based preparative regimens, single transplants, and diagnoses of NHL, HD and MM (n = 856). The median age was 49, 62% were male, and 30% received prior radiation therapy. The most common number of prior chemotherapy regimens was 2 (48%); the primary diagnosis was NHL (67%), HD (18%), MM (15%); and 90% had sensitive disease at the time of transplant. 471 (55%) are alive and 385 (45%) have died. Relapse was the most common cause of death, occurring in 303 (79%) patients. Non-relapse mortality occurred in 82 patients (21% of deaths). The most common cause of NRM was pulmonary toxicity, occurring in 26 patients, followed by secondary malignancy in 19 pts, infection (12 pts), cardiac toxicity (7 pts), other organ failure (7 pts), and other causes (11 pts). Patients who died from secondary malignancy were significantly more likely to have received prior radiation therapy (p = 0.004), to require more days of pheresis to collect stem cells (p

Description: There are relatively few reports in the medical literature describing psychosocial assessment of bone marrow transplant patients; what data exists primarily focuses on allogeneic transplant recipients. We have begun to prospectively assess psychosocial parameters of patients undergoing autologous transplantation using the Functional Assessment of Cancer Therapy-BMT (FACT-BMT) tool. The general questions consist of four subscales developed and normed in cancer patients that measure; physical well-being; social/family well-being; emotional well-being; functional well-being; and a specific module to address BMT-specific concerns. Each subscale is positively scored, with higher scores indicating better functioning. A baseline survey is collected by the social worker pre-transplant and a follow-up survey is administered and collected approximately 6 weeks post-transplant by the Transplant Coordinator. 56 consecutive patients undergoing autologous stem cell transplant have FACT-BMT data both pre-transplant and approximately one month post-discharge. Median age was 50. 52% are male; underlying diagnoses include NHL (45%), Hodgkin’s disease (32%), myeloma (16%), AML (5%), testicular cancer (2%). 93% had chemosensitive disease at the time of transplant. All patients received peripheral blood progenitor cells (PBPCs), and all received a chemotherapy-only preparative regimen. All patients were hospitalized for approximately three weeks for the transplant. For most of the variables measured by the FACT-BMT tool, there was no significant difference in pre-transplant and post-transplant scores. The one variable that did change was emotional well-being: patients scored statistically significantly higher post-transplant as compared to the pre-transplant score (p

Description: The kinetics of G-CSF PBPC mobilization are well described. CD34+cells in peripheral blood rise four days after G-CSF administration, and decline after the eighth day. VP-16 is increasingly used with G-CSF as a mobilizing regimen; however, the kinetics of mobilization are sparsely described. We retrospectively reviewed 275 patients (pts) with NHL or HD who received VP-16 plus G-CSF as a primary PBPC mobilizing regimen. 214 (78%) had NHL; 31% received prior radiation therapy; 63% were male; 85% had responsive disease. Pts received VP-16 (2 gm/m2) followed by daily G-CSF (10 mcg/kg). All pts experienced a significant WBC nadir. Pts began pheresis when their WBC recovered to 5,000. Pts were pheresed for at least 2 days or until 7.0 x 106 CD34+ cells/kg were collected; pheresis continued until a minimum of 2.0 x 106 CD34+ cells were collected. WBC nadir occurred day +6 after VP-16 and WBC recovery to 5,000 occurred day +13 (median) after VP-16. Pts were pheresed for a median of 3 days which yielded a median of 9.7 x 106 CD34+ cells/kg (range, 2.0–100.1 x 106). 72% of pts began collection on day +12, day +13, or day +14. The average CD34+ cell collection was maximal on the first 3 days of pheresis, but reasonable yields continued to be obtained for approximately 10 days of pheresis, as shown below: Figure Figure 81% collected ≥ 5 x 106 CD34+ cells/kg, and 72% collected ≥ 7 x 106 CD34+ cells/kg. The platelet count on the first day of pheresis correlated with the ability to collect 5 and 7 x 106 CD34+ cells/kg (p

Description: Purpose: An overwhelming amount of information is given to patients/caregivers undergoing Bone Marrow Transplantation at all phases of the treatment. It is difficult for many to comprehend the information and retain it. We observed that patients, while eager to be discharged home, often become apprehensive about leaving the 24 hour care given in the hospital. Based on the experience of other BMT centers, we developed a post-transplant education group for the 17 bed inpatient unit, to increase patient and family/caregiver knowledge of care and precautions that are required post-discharge as well as coping with life after transplant. Methods: The Cleveland Clinic BMT team recently designed a Bone Marrow Transplant Education Binder specific to our BMT program. Although this is used to supplement the face to face contact with the patient/caregiver, the information can still be overwhelming. The post-transplant group was designed to increase knowledge and confidence while reinforcing the information in the education binder. The information presented was designed by nursing and social work. The initial group session took place in May 2005 and has been repeated monthly since. The post-transplant information was initially presented by an outpatient BMT nurse coordinator and a BMT social worker. After 7 months the program was improved by having an inpatient BMT nurse also assist in presenting the information. All participants sign an attendance form indicating if they are the patient, family member or caregiver. The group covers topics such as coping with life after transplant, preventing infections, resuming physical and sexual activity, nutrition guidelines and graft vs. host disease. At the conclusion of the group, participants evaluate the session. The evaluation includes overall rating of the session, whether information was helpful, if participants feel better prepared for discharge, and suggestions to improve the program. Results: The post-transplant education session has been well attended by patients/caregivers with an average monthly attendance of 10 (range 6–15). The number of patients versus family members or caregivers was nearly equal. The evaluations have shown that patients/caregivers feel they are better prepared for discharge and have increased knowledge of what is required after transplant. A total of 138 evaluations were completed and 99.3% of the participants rated the session as good or excellent. Suggestions offered to improve the session included providing more detailed information about nutrition after transplant and inclusion of the dietician in the sessions. Conclusion/Recommendations: The post-transplant education group has enhanced the education of our patients/caregivers, increased their confidence and knowledge, and has become a helpful tool in new team member orientation. The recommendation of patients and caregivers to include a dietician will be implemented to improve the nutrition information provided. The benefits of this group may encourage other centers to implement similar programs. Based on the success of our post-transplant education group the possibility of a pre-transplant education group will be explored.

Description: The reactivity of NK cells and some T cell populations is regulated by KIR interactions with HLA class I molecules. Such interactions have been suggested to influence outcomes after myeloablative allogeneic HSCT. However, in NMHSCT the effect of KIR interactions on outcomes including the development of CDC has not been well described. We analyzed 51 pts who received related donor NMHSCT at our institution from 1/10/00–10/25/05. All pts received fludarabine 30 mg/m2/d x 3 days followed by total body irradiation 200 cGy (n=35) or 400 cGy (n=16) for conditioning. The median age was 54 (range, 21–64). Short tandem repeat analysis for T cell (CD3+) chimerism was performed on peripheral blood and CDC was defined as achievement of 〉95% DNA of donor origin in the CD3+ T cells. 37 (73%) of patients achieved CDC at a median time of 3.3 mos (range, 0.4–11.2). KIR genotypes were determined for recipients by PCR-rSSOP analysis. Donor HLA KIR ligands were categorized as: HLA-Cw groups C1 (+ or −); C2 (+ or −); HLA-Bw4 (+ or −); and HLA-A3 or -A11 (+ or −) [as reviewed by Farag et al. Blood2002; 100:1935–47]. Recipient KIR genotype and donor HLA KIR ligands were used to generate an inhibitory KIR score for pts from 1 to 4 corresponding to the potential number of inhibitory KIRs engaged. 7 pts had a score of 1, 27 had a score of 2, 14 had a score of 3 and 3 had a score of 4. Figure Figure The Kaplan-Meier method was used to estimate the achievement of CDC by inhibitory KIR score (figure, p=0.09). Pts with a score of 1 were less likely to achieve CDC compared to those with a score of 2 (p=0.02), while those with a score of 2 tended to be less likely to develop CDC than those with a score of 4 (p=0.07). There were no differences in CD34+ or CD3+ cell doses between any of the groups. When combined with the inhibitory KIR score data the presence of single or multiple activating KIR’s was not found to influence the development of CDC. Thus, pts with lower inhibitory KIR scores may have more active anti-donor effector cells (NK cells and T cell subsets) that may reduce donor cell chimerism. Conversely, those with higher inhibitory KIR scores may have less active populations and be more likely to achieve CDC. Given the genotypic potential to inhibit all NK cells KIR expression may be variable among different clones, and may affect the development of CDC. Further investigation of KIR expression at the cellular level rather than by genotyping alone should be pursued.

Description: Assessment of chimerism after AHSCT has been important to monitor donor hematopoietic engraftment and to assess for residual disease or relapse. Achievement of T cell (CD3+) complete donor chimerism (CDC), particularly after NM AHSCT, has been considered important to achieve a graft-vs.-malignancy effect. Formal comparisons of the onset and frequency of T cell CDC in pts treated with MY vs. NM conditioning regimens have not been well described. The current analysis compared rates of achieving T cell CDC for 116 pts transplanted from 1/10/00–5/19/06 who were categorized into the following 4 groups based upon type of transplant conditioning: 1) 200 cGy total body irradiation (TBI) + fludarabine 30 mg/m2/d × 3 days (NM200; n=47); 2) 400 cGy TBI + fludarabine (NM400; n=23); 3) MY AHSCT with busulfan/cyclophosphamide without TBI (MY-noTBI; n=31); 4) MY AHSCT with TBI (MY-TBI; n=15). All NM AHSCT pts received peripheral blood stem cells and all MY AHSCT patients received bone marrow as their stem cell source. The total nucleated cell (TNC) and CD34+ cell doses were higher in the NM AHSCT patients. 36 (31%) pts had matched unrelated donors, all with at least an 8/8 match (HLA-A, -B, -Cw, -DR) by HLA class I and II DNA-based typing [10 (21%) NM200, 7 (30%) NM400, 9 (29%) MY-noTBI, 10 (67%) MY-TBI; p=0.011]. Graft-vs-host disease prophylaxis consisted of mycophenolate mofetil and cyclosporine or tacrolimus for most pts. Short tandem repeat analysis for T cell (CD3+) chimerism was performed on peripheral blood post transplant and CDC was defined as achievement of 〉95% DNA of donor origin isolated from CD3+ T cells. Post-transplant T cell chimerism was found in both the MY and NM AHSCT groups. The number of pts who achieved CDC and the median time to its occurrence for each group was as follows: NM200 - 34 (72%) at 4 mos; NM400 - 18 (78%) at 2.7 mos; MY-noTBI - 20 (65%) at 3.3 mos; and MY-TBI - 13 (87%) at 1.3 mos. The Kaplan-Meier curves for achievement of CDC are shown above (p=0.23). The group of pts who received MY-TBI developed T cell CDC more rapidly than the NM200 pts (p=0.05). No significant differences were observed between the NM400, MY-noTBI and MY-TBI groups with regards to achieving CDC. NM conditioning with either 200 cGy or 400 cGy TBI did not show a significant difference in rate of achieving T cell CDC as compared to MY conditioning with busulfan/cyclophosphamide without TBI. This may be related in part to the higher TNC and CD34+ cell doses in the NM AHSCT pts. However, the increased TBI doses utilized for MY conditioning may more effectively suppress anti-donor immune effector cells from the recipient, which resulted in the increased CDC compared to the NM200 group. In conclusion, post-transplant monitoring for T cell CDC is important in both MY and NM AHSCT to allow for immune manipulation to maintain a state of donor-host tolerance in order to prevent graft rejection. Figure Figure

Description: We have anecdotally observed that many patients mobilized with Etoposide (VP) + filgrastim (G) collect very high numbers of CD34+ cells for autologous stem cell transplantation (ASCT). Some BMT centers have suggested that the cellular composition of an autologous graft may influence ASCT outcome. We therefore queried whether patients collecting high numbers of PBPCs (“super-mobilizers”) have a better outcome than other patients. We retrospectively reviewed 693 consecutive adult patients with Non-Hodgkin Lymphoma (NHL) or Hodgkin Lymphoma (HL) receiving an ASCT from 1/1994 through 12/2005 treated with a uniform preparative regimen of Busulfan, Cyclophosphamide and Etoposide (Bu/Cy/VP). Of these 693 patients, 350 were mobilized with VP (2 gm/m2) + G and comprised the study population. After receiving VP+G, patients were collected for a minimum of 2 days with a collection goal of 7 × 106 CD34+ cells/kg. A minimum collection of 2.0 × 106 cells was required to proceed to ASCT. Super-mobilizers were defined as collecting, and infusing, greater than 8 × 106 CD34+ cells/kg. 203 patients were super-mobilizers, while 147 collected between 2.0 and 7.95 CD34+ cells/kg. Pre-transplant performance status, LVEF, and DLCO were similar between the two groups. Super-mobilizers were slightly younger (mean 47 years old vs. 51 years old, p=0.003) and more likely to have received 2 or fewer prior chemotherapy regimens, (80% vs. 63%, p

Description: The decision to offer or not offer high dose therapy with ASCT to an individual lymphoma patient is sometimes (but perhaps mistakenly) based on the specific histology alone and not necessarily on patient characteristics, clinical manifestations, or disease behavior. Therefore, we reviewed the long-term outcome of FL, dnDLBL, and tDLBL patients, who received high dose chemotherapy (CT) with ASCT at the Cleveland Clinic, to determine if the specific histology is important. Between June 1991 and July 2004, 235 patients with FL, dnDLBL, or tDLBL in second or third remission received high dose CBV (n=7), BuCy (n=1), or BuCyVP (n=227) with ASCT. The median follow-up among survivors is 3.4 (.1–11.4) years. Patient, disease, and ASCT characteristics and outcome according to histology Variable FL (n=88) dnDLBL (n=123) tDLBL (n=24) p-value Age: median (range) 51(33–69) 50(22–71) 56(40–70) 0.021 Male sex: N (%) 47(53) 73(59) 12(50) 0.56 Years from diagnosis to ASCT: median (range) 2.6(0.4–17.5) 1.5(0.3–15.6) 3.4(1–14.0) 10 cm at ASCT: N (%) 14(16) 27(23) 4(17) 0.46 Disease progression: N (%) 35(40) 55(45) 10(42) – Death from lymphoma: N (%) 21(24) 42(34) 7(29) – Death from any cause: N (%) 31(35) 58(47) 13(54) – Kaplan-Meier freedom from progression curves accarding to histology are shown: Figure Figure Kaplan-Meier overall survival curves according to histology are shown: Figure Figure There is no significant difference in freedom from progression between FL, dnDLBL, and tDLBL patients transplanted in second or third remission. By Cox proportional univariate analysis, only male sex predicted a higher risk of progression while male sex, older age, and dnDLBL or tDLBL (compared to FL) predicted a higher risk of death. By Cox proportional multivariate analysis, no factor predicted a higher risk of progression while older age, male sex, and dnDLBL predicted a higher risk of death. In conclusion, high dose chemotherapy with ASCT leads to long-term remissions in 40–50% of FL, dnDLBL, and tDLBL patients in second or third remission. These results suggest that the distinction between these three histologies is less important than other factors in determining patient eligibility for ASCT.

Description: High-dose chemotherapy followed by autologous stem cell transplant (ASCT) is frequently performed in patients with hematologic malignancies. ASCT can result in significant nausea, pain, and discomfort. Supportive care has improved and pharmacologic therapies are frequently employed, but with limitations. Music therapy has been demonstrated to improve nausea and pain in patients undergoing chemotherapy, but little data are available in the transplant setting. We present Results from a randomized study of music therapy in patients undergoing ASCT. Patients with lymphoma or multiple myeloma undergoing ASCT were randomized to receive either interactive music therapy (MT) with a board-certified music therapist or no music therapy (No MT). The MT arm received two music therapy sessions: the first occurring as close to Day +1 as possible, the second occurring 48-96 hours later (listed as Day +1 and Day +5). Primary outcomes were perception of pain and nausea, measured on a visual analog scale which ranged from 0 to 10 (0 = no nausea, 10 = worst nausea). These were measured before and after the first music therapy session or at comparable interval for No MT patients and on days +5 and +7. Secondary outcomes were narcotic pain medication use, with pain medication doses converted to morphine equivalents and assessed daily from Day -1 to Day +5. Mood disturbance assessed by Profile of Mood States (POMS). POMS has six scales: depression, vigor, anger, tension, confusion, and fatigue. Categorical variables were compared between arms using Chi-square test, continuous variables were compared using Wilcoxon rank sum test. Repeat measures analysis of variance was used to compare outcomes between study arms over time. Eighty-two patients were enrolled: MT 37 patients, No MT 45 patients. MT arm had more African American patients (16% vs. 2%, p = 0.02), but otherwise patient characteristics in terms of age, gender, disease type, and preparative regimen were balanced. (Table 1). There was no difference in nausea between MT and No MT arms for Days 1 and +5, however, by Day +7, the MT arm had more nausea than the No MT arm (mean score 2.1 vs. 1.1, P=0.03). Although there was no difference in pain between MT and No MT patients, MT patients required significantly less morphine equivalent over the 7 study days (median 24mg vs 73mg, p =0.03). (Figure 1 and 2). There was no difference between arms for depression, vigor, anger, tension, confusion, or fatigue. In conclusion, despite having similar pain scores between both groups, the patients who received MT required significantly less narcotic pain medication use. Future study will focus on impact of music therapy on pain. Table 1 Patient characteristics Figure 1 Pain assessment Figure 1. Pain assessment Figure 2 Narcotic medication use Figure 2. Narcotic medication use Disclosures: Duong: Celgene: Honoraria, Research Funding. Off Label Use: Approved in the US but not in Europe. Hill:Celgene: Honoraria, Research Funding.

Description: Fludarabine(FLU) and 200cGy TBI is commonly used for RIC AHSCT, but we observed 12% graft rejections and a 43% incidence of disease relapse when used at our institution. We hypothesized that this might be improved with dose escalation of TBI to 400cGy. From 12/03–4/07 40 pts with hematologic malignancies received RIC AHSCT using FLU 30 mg/m2/d on days -5, -4 and -3 and then TBI 200cGy on days -1 and 0. Our analysis compared outcomes with 42 historical control pts who received 200cGy TBI from 1/00–11/03. Matched sibling donors (MSD) were used for 32(76%) pts in the 200cGy group and 26 (65%) in the 400cGy group (p=0.27); other pts had 8/8 HLA matched unrelated donors (MUD). MSD pts received cyclosporine/mycophenolate and MUD pts received tacrolimus/mycophenolate. There were no differences in diagnostic categories between the 200cGy and 400cGy groups, which included 19(45%) and 22(56%) pts with myeloid (MY) diseases, respectively, (AML most common for both) while the remaining pts with lymphoid (LY) diseases had NHL most commonly. No other baseline characteristics differed between the groups. 200cGy pts received a higher median CD34+ cell dose (6.77 vs 4.93 × 106/kg, p