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Abstract 3545

Off Label Use: Etoposide (VP16) may be considered off-label. Total body irradiation (TBI) and etoposide (VP16) is an effective conditioning regimen for allogeneic hematopoietic stem cell transplantation, but its utility in multiple unit umbilical cord blood transplantation has not been well described. This abstract shares results of a novel trial with TBI/VP/ATG for multiple unit umbilical cord blood transplantation.

Abstract 4344

Cyclosporine (CSA) and methotrexate (MTX) is a standard, effective regimen for prophylaxis of GVHD following allogeneic BMT. However, MTX increases mucosal injury and delays hematopoietic recovery in myeloablative allografts. We demonstrated in a prospective, randomized trial that CSA and mycophenolate mofetil (MMF) decreased mucositis and permitted more rapid neutrophil engraftment versus CSA/MTX in 40 patients undergoing myeloablative allogeneic BMT from matched sibling donors, with similar rates of acute and chronic GVHD, relapse, and 6-month survival. We subsequently adopted CSA/MMF as our preferred regimen for GVHD prophylaxis in matched sibling donor allografts. The objective of this analysis is to describe peri-transplant and long-term outcomes in an expanded cohort, comparing CSA/MMF with CSA/MTX. Inclusion criteria: adult patients (18 years or older) who underwent allogeneic BMT with myeloablative conditioning from a matched sibling donor with either CSA/MTX (n=76) or CSA/MMF (n=89) for GVHD prophylaxis. Median age was 45 years (range, 18–65). Diagnoses: AML (50%), CML (15%), ALL (15%), MDS (9%), NHL (6%), other (8%). Only 21% of patients had more than 2 prior regimens, and 9% had prior radiotherapy. Preparative regimens included busulfan (Bu) and cyclophosphamide (Cy) (64%), Bu/Cy + etoposide (19%), TBI-based (13%), or other (4%). All but 1 patient who received Bu/Cy + etoposide also received CSA/MTX. No other baseline characteristic differed between the groups. Median CD34+ cell dose: 1.78 x 10E6/kg overall, no difference between groups; CD3+ cell doses were incomplete for most patients who received CSA/MTX, but median values were equal between CSA/MMF and CSA/MTX patients with available data. Compared with CSA/MMF patients, those who received CSA/MTX had worse mucositis (median score 0.17 versus 1.0, P<0.001) and longer length of hospital stay for transplantation (27 versus 34 days, P<0.001). The risk of mucositis remained elevated for patients who received CSA/MTX versus CSA/MMF after adjusting for the influence of etoposide in the preparative regimens (P<0.001). Patients who received CSA/MMF had more rapid neutrophil engraftment (ANC > 500, median 11 versus 19 days, P<0.001) and platelet engraftment (platelets > 20,000, median 19 versus 24 days, P<0.001) post-transplantation. Median follow-up post allogeneic BMT was shorter for CSA/MMF patients (36 vs. 82 months, P<0.001). The probabilities of acute GVHD (all grades, grades II-IV, grades III-IV) were similar for CSA/MMF (58%, 36%, 18%) and CSA/MTX (66%, 42%, 15%) (P=NS). CSA/MMF patients experienced a lower likelihood of chronic GVHD than CSA/MTX patients (overall 42% vs. 53%, P=0.04; extensive 20% versus 37%, P=0.01). Overall infection rates were similar (P=NS), although CMV reactivation or infection was somewhat more frequent in CSA/MMF patients (58% versus 43% at 1 year, P=0.08). Five-year rates of relapse (36% versus 39%), non-relapse mortality (39% versus 39%), and overall survival (39% versus 37%) also did not differ between CSA/MMF and CSA/MTX patients. In multivariable models, CSA/MTX prophylaxis was the only factor associated with a greater risk of chronic GVHD (overall, HR 1.79, 95%CI 1.06– 3.02, P=0.03; extensive, HR 2.27, 95%CI 1.16–4.44, P=0.02). CONCLUSION: GVHD prophylaxis with CSA/MMF in matched sibling donor allografts reduces mucositis, time to engraftment, length of stay, and the risk of chronic GVHD compared with CSA/MTX, without adversely influencing rates of relapse, non-relapse mortality, or overall survival. The protective effect of CSA/MMF against chronic GVHD may be related to the fact that MMF is administered for a longer period post-transplantation than MTX, or the reduction in peri-transplant mucosal injury with MMF could result in decreased activation of potentially alloreactive T-cells. CSA/MMF is a safe and effective regimen for prophylaxis against GVHD in matched sibling donor allogeneic BMT with myeloablative conditioning.

Cyclosporine (CSA) and methotrexate (MTX) is a standard, effective regimen for prophylaxis of GVHD following allogeneic BMT. However, MTX increases mucosal injury and delays hematopoietic recovery in myeloablative allografts. We demonstrated in a prospective, randomized trial that CSA and mycophenolate mofetil (MMF) decreased mucositis and permitted more rapid neutrophil engraftment versus CSA/MTX in 40 patients undergoing myeloablative allogeneic BMT from matched sibling donors, with similar rates of acute and chronic GVHD, relapse, and 6-month survival. We subsequently adopted CSA/MMF as our preferred regimen for GVHD prophylaxis in matched sibling donor allografts. The objective of this analysis is to describe peri-transplant and long-term outcomes in an expanded cohort, comparing CSA/MMF with CSA/MTX. Inclusion criteria: adult patients (18 years or older) who underwent allogeneic BMT with myeloablative conditioning from a matched sibling donor with either CSA/MTX (n=76) or CSA/MMF (n=89) for GVHD prophylaxis. Median age was 45 years (range, 18–65).

In June 2007 four members of the University of Michigan Cardiothoracic transplant team died in a plane crash while transporting organs to an expectant transplant recipient. Matched Unrelated Donor Stem Cell transplants (MUDs) require that patients receive the preparative regimen before the hematopoeitic stem cells are transported. Our transplant program performs a “back-up” autologous harvest prior to administration of the conditioning regimen for use if the donor graft fails to arrive or if graft failure occurs. However, this practice is not uniform and insurers sometimes balk at payment. To evaluate the value of their routine collection, we reviewed the results of our center’s use of back-up marrows. 215 MUD transplants were performed at CCF from 1/95 to 12/05 and 146 recipients underwent back-up marrow collection. All recipients of adult MUD or Cord Blood transplants with hematologic malignancies in complete remission were harvested. Of 146 back-up marrows harvested, 15 patients (10%) had their back-up harvest infused. All 15 patients received their rescue marrow infusion for graft failure (adult MUD, n=12; Cord, n=3) 0.7–7.6 (median 1.1) months after the original transplant. Seven of the 15 (46%) patients had undergone full molecular matching, the other 8 (54%) patients being matched by serology for class I antigens and DNA typing for class II antigens. 9 patients were 6/6 serologic or molecular matches, 3 patients were 5/6 matches, and the 3 cord transplants were 4–5/6 matches. Deteriorating clinical status and a need for rapid engraftment was the rationale for infusion of autologous back-up marrow, as opposed to seeking additional donor cells (which potentially takes several weeks). Five patients (33%) are alive and in complete remission 14.6 to 137 (median 91) months from back-up infusion. Of these, two were bridged to a second MUD transplant. These two patients are alive and well at days 4200 and 1950 respectively. The other three have shown surprisingly durable disease free survival without repeat allogeneic transplant. Survivors Following Rescue Autologous Stem Cell Infusion Patient No. Primary Disease Transplant Material - all MUD Day of rescue infusion HLA typing of 1st transplant Second transplant Outcome 1 CML BM +29 Serologic 6/6 Yes (+560) Alive last f/u (+4200) 2 CML BM +33 Serologic 5/6 No Alive last f/u (+3363) 3 NHL BM +62 Serologic 8/8 No Alive last f/u (+2833) 4 AML Adult PBSC +230 Molecular 8/8 Yes (+1581) Alive and well (+1950) 5 AML Cord +38 Molecular 5/6 No Alive last f/u (+482) In total, 5 patients went on to a second transplant, all from adult MUD donors. Three patients died following second transplant - two from relapse and the 3rd from ARDS. Ten patients died following back-up infusion: 4 (36%) from relapse, 5 (54%) from infections and 1 from graft failure before rescue cells could engraft. Within this group, patients lived a mean of 114.5 (4–357) days from autologous rescue. Five patients were discharged from the hospital and lived a mean of 7.1 (1–12) months from discharge. In conclusion, a rescue autograft following graft failure may allow for rapid hematopoeitic recovery providing an opportunity for a second allogeneic transplant if another donor is available. In some cases it can directly result in durable remission. This procedure has saved the lives of 5 patients and should be more widely employed.

Hypogammaglobulinemia (HG) may increase the risk of infection after AHSCT. However, whether pre-transplant HG influences other outcomes after AHSCT is less certain. We therefore investigated the effect of pre-transplant serum immunoglobulin (Ig) levels on non-infectious post-transplant outcomes. From January 2001 to April 2007, 287 AHSCTs were performed at our institution. For the current analysis 65 were excluded (15 no baseline Ig data, 13 cord blood transplant, 3 <16 yrs of age, 26 with <8/8 HLA match, 8 2ndAHSCT). The median age was 43 yrs (range, 16–65), 119 (54%) were males, 90% were Caucasian, 148 had myeloid diseases (AML most common, 46%), 68 had lymphoid diseases (ALL most common, 19%) and median time from diagnosis to AHSCT was 6.4 mos (range, 0.2–106). The most common preparative regimen was busulfan/cyclophosphamide(Bu/Cy)-based (70%) followed by total body irradiation (TBI)-based conditioning. There were 134 (60%) matched related and 88 (40%) 8/8 HLA matched unrelated donors. HG was defined as serum Ig levels less than the normal ranges (NR) for IgG (717–1411 mg/dL), IgM (55–334 mg/dL) and IgA (78–391 mg/dL). The median pre-transplant Ig levels were IgG 953 (range, 18–2710) with 65 (29%) patients (pts)

Hypogammaglobulinemia (HG) may increase the risk of infection after AHSCT. However, whether pre-transplant HG influences other outcomes after AHSCT is less certain. We therefore investigated the effect of pre-transplant serum immunoglobulin (Ig) levels on non-infectious post-transplant outcomes. From January 2001 to April 2007, 287 AHSCTs were performed at our institution. For the current analysis 65 were excluded (15 no baseline Ig data, 13 cord blood transplant, 3 <16 yrs of age, 26 with <8/8 HLA match, 8 2nd AHSCT). The median age was 43 yrs (range, 16–65), 119 (54%) were males, 90% were Caucasian, 148 had myeloid diseases (AML most common, 46%), 68 had lymphoid diseases (ALL most common, 19%) and median time from diagnosis to AHSCT was 6.4 mos (range, 0.2–106). The most common preparative regimen was busulfan/cyclophosphamide(Bu/Cy)-based (70%) followed by total body irradiation (TBI)-based conditioning. There were 134 (60%) matched related and 88 (40%) 8/8 HLA matched unrelated donors. HG was defined as serum Ig levels less than the normal ranges (NR) for IgG (717–1411 mg/dL), IgM (55–334 mg/dL) and IgA (78–391 mg/dL). The median pre-transplant Ig levels were IgG 953 (range, 18–2710) with 65 (29%) patients (pts)

In June 2007 four members of the University of Michigan Cardiothoracic transplant team died in a plane crash while transporting organs to an expectant transplant recipient. Matched Unrelated Donor Stem Cell transplants (MUDs) require that patients receive the preparative regimen before the hematopoeitic stem cells are transported. Our transplant program performs a “back-up” autologous harvest prior to administration of the conditioning regimen for use if the donor graft fails to arrive or if graft failure occurs. However, this practice is not uniform and insurers sometimes balk at payment. To evaluate the value of their routine collection, we reviewed the results of our center's use of back-up marrows. 215 MUD transplants were performed at CCF from 1/95 to 12/05 and 146 recipients underwent back-up marrow collection. All recipients of adult MUD or Cord Blood transplants with hematologic malignancies in complete remission were harvested. Of 146 back-up marrows harvested, 15 patients (10%) had their back-up harvest infused. All 15 patients received their rescue marrow infusion for graft failure (adult MUD, n=12; Cord, n=3) 0.7–7.6 (median 1.1) months after the original transplant. Seven of the 15 (46%) patients had undergone full molecular matching, the other 8 (54%) patients being matched by serology for class I antigens and DNA typing for class II antigens. 9 patients were 6/6 serologic or molecular matches, 3 patients were 5/6 matches, and the 3 cord transplants were 4–5/6 matches. Deteriorating clinical status and a need for rapid engraftment was the rationale for infusion of autologous back-up marrow, as opposed to seeking additional donor cells (which potentially takes several weeks). Five patients (33%) are alive and in complete remission 14.6 to 137 (median 91) months from back-up infusion. Of these, two were bridged to a second MUD transplant. These two patients are alive and well at days 4200 and 1950 respectively. The other three have shown surprisingly durable disease free survival without repeat allogeneic transplant.

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

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.

Purpose: The lived experience of patients undergoing myeloablative (allos) compared to non-myeloablative (mini allos) allogeneic BMT is unclear due to a lack of empirical psychosocial studies. This study compares patient characteristics, psychosocial profiles, and outcomes of patients undergoing allos and mini allos. Methods: From 3/2003 to 12/2005, 125 patients (99 allos and 26 mini allos), completed three psychometric instruments: FACT-BMT (QOL), Brief COPE (coping), and POMS short form (mood states). Patients completed these instruments post discharge for allos and post infusion for mini allos, day 100, 6 months, and 1 year post transplant. P<.05 is utilized to indicate statistical significance. Results: Relative to allos, mini allos are older (P<.001), married longer (P=.004), have more children (P=.036), are more likely to be retired (P=.025), have more anxiety (P=.039), and a longer interval from diagnosis to transplant (P<.001). Several medical characteristics differ between groups, including diagnosis, preparative regimen, and source of hematopoietic cells. Mini allos engraft faster (P<.001) than allos. Although percentage of patients requiring post-transplant readmission is similar (>85%) between groups, duration of readmission is shorter for mini allos than for allos (median 7 vs.13 days). Outcomes of GVHD, relapse, and survival did not differ significantly between the subgroups; death rate at 1½ year follow-up for allos is 50.5% and for mini allos 42.3%. There are only two baseline differences in psychosocial functioning: social well-being (FACT-QOL) in mini allos is better (P=.014) while planning (COPE) is worse (P=.044). At first post-infusion visit, mini allos have better scores on four FACT-QOL scales: functional well-being (P=.031), additional concerns (P=.019), trial outcome index (P=.010), and total score (P=.046), and worse scores on positive reframing (P=.040). By day 100, minis continue to have better scores on three FACT-QOL scales: additional concerns (P=.012), trial outcome index (P=.013), and total score (P=.031), and worse scores on COPE’s planning scale (P=.034). Due to patient and/or staff omissions in data collection and patient death rates, there are fewer patients who have 6 and 12 month assessments, but among this subset COPE’s use of instrumental support at 6 months is worse for mini allos (P=.029), while positive reframing is worse among mini allos at both 6 months (P=.026) and 12 months (P=.048). Conclusions: Mini allos have better QOL than allos up to 100 days. However, that QOL returns close to baseline by one year post transplant for surviving patients of both subgroups is encouraging. That mood state scores for both groups are close to baseline at one year, and depression and tension scores are lower suggests a positive outcome. That coping scores for both groups become close to baseline, except for emotional support being used less, indicates return to more independent emotional functioning at one year. The lack of more significant differences between subgroups is surprising. Further analysis of the return to baseline functioning with a larger sample of patients in both subgroups would be of interest.

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.

Purpose: The lived experience of patients undergoing myeloablative (allos) compared to non-myeloablative (mini allos) allogeneic BMT is unclear due to a lack of empirical psychosocial studies. This study compares patient characteristics, psychosocial profiles, and outcomes of patients undergoing allos and mini allos.

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.

Quality of life (QOL) data concerning allogeneic BMT recipients is relatively sparse. We surveyed allogeneic BMT recipients at baseline, one month post-transplant, and one year from transplant attempting to determine fluctuations in QOL over time. We used the FACT-BMT tool, which consists of five component scores, including physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and additional concerns (AC). PWB, SWB, and FWB uses a 0–28 point scale while EWB ranges from 0–24. Fifty-three patients were initially entered into this analysis, all of whom received ablative allogeneic transplants from 6/2003 to 6/2005. Median age was 46 years; the majority (57%) were female; underlying diagnoses included AML (42%), ALL (23%), MDS (13%), and other (22%). Median time from diagnosis to transplant was rapid, at 5.2 months. Fifty-one percent had a matched related donor, and 49% had a matched unrelated donor. As of August 2005, 70% of these 53 patients are alive. This analysis compares scores obtained one month from transplant and one year from transplant to baseline values. The average hospital length of stay for this ablative transplant was 29 days. One month after transplant, 21% of patients had grade 2–4 acute GVHD. The median WBC was 4.4 K/μL and the median platelet count was 51 K/μL. When surveyed one month post-transplant, not surprisingly, patients had a significant deterioration of physical well-being and functional well-being scores as shown in the table below. However, this was coupled by a significant increase in emotional well-being: FACT-BMT SCORES: median (range) Component Baseline (n = 53) 1-month post-transplant BMT (n = 53) 1-month p-value compared to baseline 12-months post-BMT (n = 23) 12-month p-value compared to baseline PWB 21 (6–28) 18 (2–26) p < 0.001 21 (3–28) 0.82 FWB 17 (0–27) 13 (4–23) p = 0.006 17 (6–27) 0.46 EWB 17 (3–24) 19 (1–24) p < 0.001 19 (5–24) 0.015 The decrease in PWB and FWB was expected given the rigors of an ablative allogeneic transplant, but the significant rise in EWB was surprising. This may reflect a sense of accomplishment, relief, and optimism among patients concerning their underlying diagnosis and treatment. Twenty-three patients were available to complete the survey tool 12 months after transplant. This was a favorable cohort of patients with continued remissions. Fifty-two percent of these 23 patients, however, did have some degree of chronic graft-versus-host disease. The PWB and SWB scores returned to baseline, and the enhanced EWB scores persisted. Thus, the negative impact of the BMT on PWB and SWB was self-limited. The underlying mechanisms of the sustained EWB improvement one year post-transplant may reflect the fact that these patients were doing well clinically. Further analysis of the early rise in emotional well-being after ablative allogeneic BMT would be of interest.

Quality of life (QOL) data concerning allogeneic BMT recipients is relatively sparse. We surveyed allogeneic BMT recipients at baseline, one month post-transplant, and one year from transplant attempting to determine fluctuations in QOL over time. We used the FACT-BMT tool, which consists of five component scores, including physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and additional concerns (AC). PWB, SWB, and FWB uses a 0–28 point scale while EWB ranges from 0–24. Fifty-three patients were initially entered into this analysis, all of whom received ablative allogeneic transplants from 6/2003 to 6/2005. Median age was 46 years; the majority (57%) were female; underlying diagnoses included AML (42%), ALL (23%), MDS (13%), and other (22%). Median time from diagnosis to transplant was rapid, at 5.2 months. Fifty-one percent had a matched related donor, and 49% had a matched unrelated donor. As of August 2005, 70% of these 53 patients are alive. This analysis compares scores obtained one month from transplant and one year from transplant to baseline values. The average hospital length of stay for this ablative transplant was 29 days. One month after transplant, 21% of patients had grade 2–4 acute GVHD. The median WBC was 4.4 K/μL and the median platelet count was 51 K/μL. When surveyed one month post-transplant, not surprisingly, patients had a significant deterioration of physical well-being and functional well-being scores as shown in the table below. However, this was coupled by a significant increase in emotional well-being:

We have previously demonstrated the value of evaluating patients with NHL undergoing autologous HSCT at 2 years post-transplant; high grade lymphoma patients in CCR 2 years post-transplant are cured, whereas patients with intermediate and low grade histologies are at ongoing risk of relapse. We elected to perform a similar analysis of AHSCT patients. We retrospectively reviewed 161 consecutive AHSCT recipients who had a minimum of 2 years follow-up and who were alive 2 years post AHSCT. Patients received their transplants from 7/1988 to 7/2002. Median age was 36 years; 75% had myeloid malignancies and 25% lymphoid; AML was the most common diagnosis (39%) followed by CML (29%), ALL (14%), NHL (10%), MDS (6%), and myeloma (2%). 98% received bone marrow alone as the hematopoietic stem cell source; 98% received a busulfan/cyclophosphamide-based preparative regimen. 129 (80%) had a matched related donor. Of those patients alive 2 years post AHSCT, 31 patients (19%) have subsequently died, with a median follow up of 6 years. Relapse was the cause of death in 29%; GVHD in 35%; secondary malignancy in 7%; infections in 16%. Patients with myeloid malignancies faired better than those transplanted with lymphoid malignancies, as shown below; (p= 0.04) Figure Figure When we analyzed the pts who developed their first episode of any chronic GVHD or extensive chronic GVHD there were no significant differences between lymphoid and myeloid malignacy patients. Patients receiving a matched sibling donor transplant did not have a plateau in their survival curve, and it continued to inexorably decline. Patients receiving a matched unrelated donor transplant did have a plateau of their survival curve if patients survived at least 3 years (p=0.03). We conclude that the significant majority of patients alive after AHSCT do well with extended follow-up. The graft vs. tumor effect appears to be more robust in myeloid malignancies as compared to lymphoid malignancies. Although most of these patients do well with extended follow-up, the lack of a plateau in the survival curve for patients receiving a matched sibling donor allogeneic BMT warrants additional study.

Class I and II DNA-based HLA typing has resulted in improved outcomes in MUD ABMT compared to that observed with HLA serologic typing methods. Since MUDs do not necessarily possess the same linkage of HLA genes on haplotypes as found in matched sibling donors (MSD) it is important to determine the specific alleles present through DNA-based methods in order to improve matching between recipients and donors. We analyzed 146 consecutive hematologic malignancy patients (pts) who underwent ABMT at our institution from 1/7/99–2/4/04, to compare outcomes of 41 MUD and 105 MSD pts. All pts were matched at HLA-A, B, C, and DRB1 by at least low to intermediate resolution using either PCR-sequence specific priming or PCR-sequence specific oligonucleotide probing using Class I and II DNA-based HLA typing. All pts received a busulfan/cyclophosphamide (Bu/Cy)-based preparative regimen. All MUD ABMTs were CD8+ T cell depleted while all MSD ABMTs were T cell replete. GVHD prophylaxis for MUD pts consisted of FK506 and methotrexate while MSD pts received cyclosporine and methotrexate or mycophenolate mofetil. There were no differences between MUD or MSD pts in terms of sex, age, race, prior radiation therapy, or donor-pt gender. Primary diagnoses were comparable except the MSD group had more CML pts (19 vs. 0) (p=0.01 for all diagnoses). There were no differences between MUD and MSD pts regarding infection, acute GVHD, acute grade 3–4 GVHD, chronic GVHD or extensive chronic GVHD. MUD pts as compared to MSD pts had higher graft failure rates (12% vs. 3%, p = 0.019); lower relapse-free survival (median 5.4 mos vs. 10.7 mos, p=0.037); higher 100-day mortality (37% vs. 21%, p=0.05), and lower overall survival (median 5.7 mos vs.13.6 mos, p=0.036). Deaths occurred in 30 (73%) of MUD pts and 61 (58%) of the MSD pts with disease relapse followed by GVHD as the most common causes of death. Since CML pts were only in the MSD group, we repeated the analysis excluding these pts and there were no longer any significant differences between the MUD and MSD pts in 100 day mortality (p=0.12), relapse-free survival (median 5.4 mos vs. 6.5 mos, p=0.22), or overall survival (median 5.7 mos vs. 10.0 mos, p=0.18). For further purposes of comparison, we also analyzed 112 consecutive ABMT pts (31 MUD, T cell depleted; 81 MSD, T cell replete; Bu/Cy-based preparative regimens for all pts) previously transplanted at our institution from 4/93–11/98 during which time only HLA serologic and Class II DNA-based typing was used. In this earlier pt cohort, the MUD pts had a significantly higher incidence of acute GVHD (p<0.001), lower 100-day mortality (52% vs. 12%, p<0.001), lower relapse-free survival (p=0.001) and lower overall survival (2.6 mos vs. 32.5 mos, p=0.001) than the MSD patients. We conclude that Class I and II DNA-based HLA typing is important and can improve outcome in MUD ABMT. Further investigation with high resolution HLA typing methods may continue to improve outcomes with MUD ABMT.

Class I and II DNA-based HLA typing has resulted in improved outcomes in MUD ABMT compared to that observed with HLA serologic typing methods. Since MUDs do not necessarily possess the same linkage of HLA genes on haplotypes as found in matched sibling donors (MSD) it is important to determine the specific alleles present through DNA-based methods in order to improve matching between recipients and donors. We analyzed 146 consecutive hematologic malignancy patients (pts) who underwent ABMT at our institution from 1/7/99–2/4/04, to compare outcomes of 41 MUD and 105 MSD pts. All pts were matched at HLA-A, B, C, and DRB1 by at least low to intermediate resolution using either PCR-sequence specific priming or PCR-sequence specific oligonucleotide probing using Class I and II DNA-based HLA typing. All pts received a busulfan/cyclophosphamide (Bu/Cy)-based preparative regimen. All MUD ABMTs were CD8+ T cell depleted while all MSD ABMTs were T cell replete. GVHD prophylaxis for MUD pts consisted of FK506 and methotrexate while MSD pts received cyclosporine and methotrexate or mycophenolate mofetil. There were no differences between MUD or MSD pts in terms of sex, age, race, prior radiation therapy, or donor-pt gender. Primary diagnoses were comparable except the MSD group had more CML pts (19 vs. 0) (p=0.01 for all diagnoses). There were no differences between MUD and MSD pts regarding infection, acute GVHD, acute grade 3–4 GVHD, chronic GVHD or extensive chronic GVHD. MUD pts as compared to MSD pts had higher graft failure rates (12% vs. 3%, p = 0.019); lower relapse-free survival (median 5.4 mos vs. 10.7 mos, p=0.037); higher 100-day mortality (37% vs. 21%, p=0.05), and lower overall survival (median 5.7 mos vs.13.6 mos, p=0.036). Deaths occurred in 30 (73%) of MUD pts and 61 (58%) of the MSD pts with disease relapse followed by GVHD as the most common causes of death. Since CML pts were only in the MSD group, we repeated the analysis excluding these pts and there were no longer any significant differences between the MUD and MSD pts in 100 day mortality (p=0.12), relapse-free survival (median 5.4 mos vs. 6.5 mos, p=0.22), or overall survival (median 5.7 mos vs. 10.0 mos, p=0.18). For further purposes of comparison, we also analyzed 112 consecutive ABMT pts (31 MUD, T cell depleted; 81 MSD, T cell replete; Bu/Cy-based preparative regimens for all pts) previously transplanted at our institution from 4/93–11/98 during which time only HLA serologic and Class II DNA-based typing was used. In this earlier pt cohort, the MUD pts had a significantly higher incidence of acute GVHD (p<0.001), lower 100-day mortality (52% vs. 12%, p<0.001), lower relapse-free survival (p=0.001) and lower overall survival (2.6 mos vs. 32.5 mos, p=0.001) than the MSD patients. We conclude that Class I and II DNA-based HLA typing is important and can improve outcome in MUD ABMT. Further investigation with high resolution HLA typing methods may continue to improve outcomes with MUD ABMT.

We have previously demonstrated the value of evaluating patients with NHL undergoing autologous HSCT at 2 years post-transplant; high grade lymphoma patients in CCR 2 years post-transplant are cured, whereas patients with intermediate and low grade histologies are at ongoing risk of relapse. We elected to perform a similar analysis of AHSCT patients. We retrospectively reviewed 161 consecutive AHSCT recipients who had a minimum of 2 years follow-up and who were alive 2 years post AHSCT. Patients received their transplants from 7/1988 to 7/2002. Median age was 36 years; 75% had myeloid malignancies and 25% lymphoid; AML was the most common diagnosis (39%) followed by CML (29%), ALL (14%), NHL (10%), MDS (6%), and myeloma (2%). 98% received bone marrow alone as the hematopoietic stem cell source; 98% received a busulfan/cyclophosphamide-based preparative regimen. 129 (80%) had a matched related donor. Of those patients alive 2 years post AHSCT, 31 patients (19%) have subsequently died, with a median follow up of 6 years. Relapse was the cause of death in 29%; GVHD in 35%; secondary malignancy in 7%; infections in 16%. Patients with myeloid malignancies faired better than those transplanted with lymphoid malignancies, as shown below; (p= 0.04)