Abstract 366 Background: In recent years, donor hematopoietic stem cells have been increasingly c... more Abstract 366 Background: In recent years, donor hematopoietic stem cells have been increasingly collected by leukapheresis using the PBSC procedure in GCSF-stimulated donors as an alternative to the traditional surgical marrow collection process. However, the relative medical safety and health-related quality-of-life (HRQoL) impact of the two procedures on donors have not been systematically compared. In 2004 the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) initiated a randomized trial that included evaluation of potential medical and HRQoL differences between BM and PBSC donors. Data collection for the trial is complete for the time points shortly pre-and post-donation. Donors and Methods: The goals of the analyses were to examine (a) pre- and post-donation differences on key variables by donation type, and (b) the association of pre-donation variables with donor recovery. Participants included 273 adult matched unrelated BM (n=131) and PBSC (n=142) donors who donated at U.S. centers between July, 2004 and October, 2009 and completed pre-, 48 hours post-, and weekly post-donation telephone interviews until fully recovered defined as three consecutive symptom-free weeks. Basic socio-demographics, physical and mental health status, and donation-related perceptions were self-reported by donors and key clinical variables were collected from donor centers. Odds-ratios for dichotomous variables and t-tests for continuous variables were used to examine differences in pre- and post-donation variables by donation type and to examine the potential effects of pre-donation variables on recovery at 8-weeks post-donation. Results: At pre-donation, BM donors were significantly more likely to be married (OR=1.82; 1.11–2.94), employed (OR=2.98; 1.05–8.44), and to feel prepared for donation (OR=1.89; 1.01–3.45) than PBSC donors. At 48-hours post-donation, BM donors reported significantly more physical effects of donation including greater intensity (t=3.11; p
Introduction: Although melphalan at a dose of 140 mg/m2 (MEL-140) is known to be an effective pre... more Introduction: Although melphalan at a dose of 140 mg/m2 (MEL-140) is known to be an effective preparative regimen for autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM) patients, there are very few studies comparing it to the most commonly used dose of 200 mg/m2 ( MEL-200). Methods: We retrospectively reviewed the records of all myeloma patients who underwent an ASCT between 2001 and 2010 at our institution. We then identified patients who received melphalan as their preparative regimen at doses of 140 mg/m2 or 200 mg/m2. Patients who received any other drug as conditioning regimen or had more than one ASCT or had documented amyloidosis were excluded. Data were collected for variables known to possibly affect prognosis of MM patients. We assessed effect of melphalan dose on toxicities and outcomes. Results: A total of 129 eligible patients were identified, with 33 receiving MEL-140 and 96 receiving MEL-200. As was expected significantly higher percentage of patients in the MEL-140 arm were older than 65 years (P=<0.001) or had cardiac ejection fraction…
Introduction: The adverse events associated with hematopoietic stem cell donation have been exten... more Introduction: The adverse events associated with hematopoietic stem cell donation have been extensively studied. There is an increasing literature linking psychological factors including stress, anxiety and depression to higher levels of inflammatory burden leading to poorer post-procedural outcomes including longer hospital stays and increased pain perception. Here, we aimed to evaluate whether pre-donation health related quality of life (HRQoL) markers predict toxicity profile and stem cell yield following stem cell donation in healthy donors. Methods: The study population included adult granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cell (PBSC) related donors (RD) (n= 157) and unrelated donors (URD) (n=179) who were enrolled in Related Donor Safety Study (RDSafe) and Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 clinical trials. Pre-donation HR QoL was assessed using the Short-Form (SF-8) in RDSafe and SF-12 questionnaire in BMT CTN 0201 (higher score is better). Pain and toxicity were collected on study specific forms. The primary outcome was the incidence of skeletal pain on day 5 of G-CSF administration. The secondary outcomes were the incidence of skeletal pain and highest toxicity level across selected body symptoms at 1 month, 6 months and 1-year post-donation. Another secondary outcome included CD34+ per liter of blood processed (x10 6/L) on day 5 of G-CSF as a measure of collection yield. The association between pre-apheresis HRQOL measures and pain and acute toxicities was characterized using means and SDs and compared using the t-test. Association between HRQoL and cell yield was assessed using the Pearson correlation coefficient. RD and URD were analyzed separately. Results: URDs were younger than RDs (median age 35 vs. 63). A higher proportion of RDs were female (50% vs. 40%) and obese (41% vs. 35%). A higher proportion of RD PBSC donations required 2 days or more (44% vs 21%). More RDs were collected with lower volume procedures (<18L, 28% vs. 16%), and required a central line (28% vs. 11%). RDs were more likely to report pre-donation grade 1-2 pain (27% vs. 8%) and other toxicities (16% vs. 6%). The mean pre-donation physical component summary (PCS) and mental component summary (MCS) score of RDs were 54.5 (SD 7.0) and 55.1 (SD 5.8), respectively . In the univariate analysis (table 1), pre-donation lower PCS score of RDs was associated with significantly more grade 2-4 pain at 1 month (p=0.0038) and 1-year post-donation (p=0.0099) (Table 1). In multivariable analysis (table 2), pre-donation PCS remained significantly associated with grade 2-4 pain 1-month post-donation (p=0.0098). More specifically, RDs with pre-donation PCS scores in the higher quartile were less likely to experience pain compared with donors with PCS scores in the lower quartile (OR 0.1; 95% CI 0.01-0.83; p=0.005). There was also a trend toward increased grade 2-4 pain at 1-year post-donation among RDs with lower PCS score (p=0.0176). Other outcomes such as pain at day 5 of G-CSF, other toxicities at day 5 of G-CSF, 1 month, 6 months and 1-year post-donation were not associated with pre-donation PCS score. Similarly, there was no significant association between RD pre-donation MCS score and collection-related symptoms at any time point. The mean pre-donation PCS and MCS scores of URDs were 56.2 (SD 4.7) and 54.5 (SD 5.5), respectively . In a univariate analysis, there was no association between PCS score or MCS score and donation associated pain and toxicities at any time point post-donation. Due to low event rates, multivariable analysis was not performed in the URD setting. Based on the multivariable regression analysis, there was no correlation between pre-apheresis HRQoL score (PCS or MSC) and PBSC collection yield in either the RD or URD setting. Conclusion: Our study demonstrates that pre-donation QoL markers are significantly associated with the toxicity profile after PBSC donation in the RD setting as adult RD with lower pre-donation physical QOL experience increased levels of pain after a PBSC collection procedure. There were no such associations found in URD in this small sample. Our findings may help clinicians to identify donors at higher risk of pain with donation, and lead to personalized information and interventions (e.g. increased analgesia) for specific donors. Future study with a larger sample is required to validate the results. Figure 1 Figure 1. Disclosures Farhadfar: Incyte: Consultancy. Stefanski: Novartis: Honoraria. Pulsipher: Equillium: Membership on an entity's Board of Directors or advisory committees; Adaptive: Research Funding; Jasper Therapeutics: Honoraria. Shaw: mallinkrodt: Other: payments; Orca bio: Consultancy.
Abstract 4462 The hematopoietic stem cell transplant comorbidity index (HCT-CI) was developed as ... more Abstract 4462 The hematopoietic stem cell transplant comorbidity index (HCT-CI) was developed as a risk assessment tool in patients undergoing allogeneic HCT. HCT-CI scores have been shown to be associated with non-relapse mortality (NRM) and overall survival (OS) in retrospective studies. However the correlation between HCT-CI scores and post-transplant resource utilization has not been investigated. Previously, we reported a correlation between the HCT-CI and increased hospitalization in the matched related donor setting (Szwed E, et al. Blood. 2010; 116: 4748a). In the unrelated donor population, we retrospectively analyzed 229 consecutive patients who had undergone matched unrelated donor stem cell transplant between January 2001 and December 2008. Donor stem cell sources included peripheral blood (n=90), bone marrow (n=67), and umbilical cord blood (n=72). Conditioning regimens were divided into myeloablative (MA, n = 159), reduced intensity (RIC, n = 28) and non-myeloablative (NMA, n = 42). HCT-CI scores were calculated by method of Sorror (Sorror ML, et al. Blood. 2005 106: 2912–19). Median follow-up was 6.2 years. Consistent with prior findings, HCT-CI correlated with NRM (rs = 0.16, p = 0.015) and overall survival (median survival when score ≤ 3 = 761 days vs score > 3 = 212 days [p = 0.0005]). A negative correlation was found between HCT-CI score and total hospital days as well as days spent in hospital after discharge from initial transplant hospitalization, implying that the higher the score the less time spent in the hospital after transplant (Table 1). However, this correlation disappeared when adjusted for patient survival. We also noted that the majority of readmissions and hospitalizations occurred within the first 100 days from transplant. In subgroup analysis, we found a relationship between HCT-CI score and total hospital days (rs = 0.37, p = 0.0032) and in number of hospital days after discharge for transplant (rs = 0.35, p = 0.0047) for patients who underwent a myeloablative cord blood transplant, even after adjusting for patient survival. In summary, our analysis validated the correlation between HCT-CI score and NRM/overall survival, but we were unable to find a statistically significant correlation between HCT-CI and hospitalizations, except in the myeloablative cord blood setting. We found that most readmissions and hospital days occur early in the post-transplant period (<100 days). We hope further analyses will help unravel these apparent discrepancies in this particular transplant population.Table 1:Spearman Correlation Coefficients between HCT-CI vs. Readmissions and Hospital DaysNMedian Age (yrs)Readmission*Hospital days for Transplant#Admissions after Transplant#Total#Total22935.4−0.002 (0.98)0.0068 (0.92) −0.004 (0.95)−0.26 (<0.0001)0.041 (0.54)−0.16 (0.023)0.11 (0.089)MA−NC9638.9−0.12 (0.24)−0.11 (0.32) −0.17 (0.10)−0.04 (0.68)0.093 (0.36)−0.11 (0.32)0.097 (0.34)MA−C6314.30.11 (0.39)0.093 (0.49) 0.13 (0.32)0.055 (0.67)0.35 (0.0047)0.14 (0.32)0.37 (0.0032)NMA4249.9−0.80 (0.61)−0.32 (0.045) 0.15 (0.35)0.020 (0.90)0.073 (0.65)−0.43 (0.0064)−0.14 (0.39)RIC2847.9−0.10 (0.61)0.18 (0.36)0.011 (0.95)−0.19 (0.35)0.095 (0.63)0.015 (0.94)0.31 (0.11)MA-NC=myeloablative, no cord; MA-C=myeloablative cord; NMA=non-myeloablative; RIC=reduced intensity;() p values in parentheses#Top numbers refer to unadjusted values, bottom are adjusted for patient survival Statistically significant values are bold Disclosures: No relevant conflicts of interest to declare.
Abstract 2023 Background: The role of tandem and salvage autologous stem cell transplant (ASCT) i... more Abstract 2023 Background: The role of tandem and salvage autologous stem cell transplant (ASCT) in multiple myeloma (MM) has been a subject of interest for many myeloma investigators. Further, the role of tandem ASCT in patients achieving very good partial remission (VGPR) or complete remission (CR) has not been studied prospectively. Methods: We conducted a prospective phase II clinical trial in which enrolled MM patients are assessed after the first ASCT. Patients achieving ≤ partial remission (PR) were offered 2nd tandem ASCT followed by maintenance therapy. Patients that were found to be ≥VGPR were offered maintenance therapy followed by salvage ASCT at the time of relapse. Busulfan 0.75 mg/kg PO q 6 hr days -8 through -5, Cyclophosphamide (Cy) 60 mg/kg IV days -3 and -2, and Etoposide 10 mg/kg IV days -4 to -2 were used as the conditioning regimen for the first ASCT. Patients receiving a second ASCT received 96-hour (days -6 to -3) continuous IV Cy 6 gr/m2 and low dose total body irradiation (loTBI) 600 cGy (days -2 and -1). Etoposide was omitted if patients were ≥65 years. Melphalan 140 mg/m2 was used in lieu of TBI if prior irradiation did not allow for TBI. Results: Between the years 2001–2009, 76 patients were enrolled into the study. 54 patients achieved ≥VGPR. 31 patients had ≤ PR and were offered ASCT. Of these patients, 21 patients ultimately received tandem ASCT and 1 patient had tandem autologous-allogeneic transplants. Reasons for not receiving the planned tandem ASCT were lack of socioeconomic resources, physical co-morbidities, and patient refusal. There were no treatment related mortalities in the ASCT patients. Progression-free (PFS) and overall (OS) were compared between the single ASCT (n=54) and tandem ASCT (n=21) groups. The median PFS for the single ASCT group was 27 months (range, 3–107) and 21 months (range, 7–101) in the tandem group (P=0.814). OS was 76 months (range, 5–144) vs. 38 months (range, 12–128), respectively (P=0.121). At the time of submission, a total of 26 (48%) patients in the single ASCT group and 6 (30%) patients in the tandem group are still alive. Among the tandem patients, 2 later underwent salvage ASCT and 3 went on to receive non-myeloablative allogeneic transplants. In the single ASCT group, 6 had salvage ASCT and 7 had allogeneic SCT. All salvage transplants were done at a median of 30 months (range, 8–90) from the last ASCT. Patients who declined tandem transplant had a median PFS of 20 months (range 4–38). Patients who did not quality for tandem ASCT had a median PFS of 28 months (range 3–107) (p–0.08). Median OS between the two groups was 53 months (range 5–95) and 57.5 months (12–144), respectively (p–0.67). Conclusions: Patients who achieve ≥VGPR after 1st ASCT have similar PFS and a trend toward better OS than patients who had tandem ASCT. Thus, the use of such response criteria may identify a group of lower risk patients that will do well without upfront tandem ASCT. Disclosures: No relevant conflicts of interest to declare.
Background Early response to induction therapy for AML assessed by bone marrow (BM) evaluation on... more Background Early response to induction therapy for AML assessed by bone marrow (BM) evaluation on day 14 (D14) post chemotherapy is considered an important predictor of achieving complete remission (CR). Our aim was to identify clinical and laboratory factors influencing the probability of CR in AML patients (pts) with positive D14 BM without receiving further chemotherapy. Methods Records of pts with AML treated between 1998 and 2011 were retrospectively reviewed to identify subjects with positive D14 BM who did not receive re-induction chemotherapy. The distribution of following variables such as age, white blood cell count (WBC) at the time of induction therapy, BM cellularity, percentage of blasts, disease status, and risk was compared by the univariate analysis. Recovery BM status (positive vs. negative for disease) as the response variable and age, WBC at the time of induction therapy, BM cellularity, percentage of blasts, disease status, and risk as explanatory variables were assessed by the logistic regression analysis. Poor risk AML was defined as the presence of adverse karyotype, treatment related disease or presence of antecedent hematologic disorder. Positive BM was defined as either cellularity ≥20% or ≥5% myeloblasts by IHC staining. CR was defined according to IWG 2003 criteria. Results 169/378 (44%) had a positive D14 BM after induction therapy and 92/169 (54%) did not receive re-induction chemotherapy. 68/92 (74%) underwent repeated BM evaluation at WBC recovery, which occurred 4-5 weeks after induction chemotherapy. Recovery BM showed refractory AML in 38/68 (56%) of cases. However, in 30/68 (44%) cases CR was achieved despite previously positive D14 BM. As demonstrated in Table 1, clinical and laboratory characteristics of the CR and refractory groups showed significant differences in the absolute percentage of D14 myeloblasts, abnormal vs. normal myeloblast phenotype, de novo vs. relapse disease status, and risk stratification. Higher blast percentage (P=.0016) was associated with significantly higher probability of having refractory AML and each 1% increase blasts on D14 BM increased the odds of refractory AML on recovery BM by 6% (OR=1.06 95% CI 1.022-1.099) (Figure 1) In contrast, no clear association between D14 BM cellularity and the recovery BM status was found. The results from the multivariate analysis were comparable with that from the univariate analysis. Blast percentage, disease status, and AML risk were strongly and jointly associated with the status of BM recovery. By using a logistic model including myeloblast percentage, myeloblast phenotype, disease status, and AML risk category we correctly predicted 31 refractory AML cases out of 38 (sensitivity = 82%) and we correctly predicted 23 CR cases out of 30 (specificity = 77%). For example, based on our formula, which incorporated blast percentage, disease status, and AML risk we estimated that in a patient with de novo, not a poor risk AML with 5% blasts on D14 BM the probability of positive recovery BM status was 6%, whereas in a patient with relapsed poor risk AML and 50% blasts on D14 BM the probability of positive recovery BM status was 98%. Conclusions Significant proportion of pts with positive D14 BM may achieve CR without subsequent chemotherapy administration. Low blast percentage, absence of phenotypically abnormal myeloblasts, de novo diagnosed AML, and absence of poor risk AML are associated with a significantly higher probability of CR. We developed a useful formula for predicting remission status in the setting of positive D14 BM that would be valuable in clinical trial protocols involving decision trees for re-induction chemotherapy. Disclosures: No relevant conflicts of interest to declare.
Abstract 224 Umbilical cord blood transplantation (UCBT) is an alternative stem cell source for p... more Abstract 224 Umbilical cord blood transplantation (UCBT) is an alternative stem cell source for patients with leukemia in need of an allogeneic transplant without a suitable marrow or peripheral blood stem cell donor. Extensive resources have been mobilized to increase the number of UCB donations from patients of diverse ethnic and racial backgrounds, in an effort to provide an adequate stem cell source for patients of ethnic minorities who may have a difficult time finding a compatible unrelated marrow or peripheral blood stem cell donor. We analyzed the association of race/ethnicity and outcomes of 907 patients receiving unrelated single unit UCBT from 1995 to 2006 for AML, ALL, CML, and MDS and who were reported to the CIBMTR. Race/ethnicity was reported by the transplant centers and included 612 Whites, 145 Blacks and 128 Hispanics. Patients received a variety of conditioning and graft versus host disease (GVHD) prophylaxis regimens. Most patients (72%) received ablative conditioning. Median ages at transplant were 8 years…
Cytomegalovirus (CMV) infection was detected in 65 of 143 (45%) autologous bone marrow transplant... more Cytomegalovirus (CMV) infection was detected in 65 of 143 (45%) autologous bone marrow transplant (BMT) patients. CMV pneumonitis occurred in only 2% of the patients and CMV retinitis occurred in none. Infection occurred in half of the 40 initially seronegative patients and 47% of the 94 initially seropositive patients. Among initially seropositive patients, platelet recovery was slower in infected patients than in those not infected (97 v 35 days median, P = .003), and neutrophil recovery was slightly delayed in infected patients (31 days v 24 days, P = .02). Although the incidence of CMV infection was comparable in autologous and allogeneic BMT patients, CMV pneumonitis was less frequent in autologous BMT patients (2% v 12%, P less than .001). The risk for CMV pneumonitis in autologous BMT patients was comparable with that in allogeneic BMT patients without graft-v-host disease (GVHD) (2% v 6%), but significantly lower than the risk in allogeneic BMT patients with GVHD (2% v 23%, ...
Abstract 366 Background: In recent years, donor hematopoietic stem cells have been increasingly c... more Abstract 366 Background: In recent years, donor hematopoietic stem cells have been increasingly collected by leukapheresis using the PBSC procedure in GCSF-stimulated donors as an alternative to the traditional surgical marrow collection process. However, the relative medical safety and health-related quality-of-life (HRQoL) impact of the two procedures on donors have not been systematically compared. In 2004 the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) initiated a randomized trial that included evaluation of potential medical and HRQoL differences between BM and PBSC donors. Data collection for the trial is complete for the time points shortly pre-and post-donation. Donors and Methods: The goals of the analyses were to examine (a) pre- and post-donation differences on key variables by donation type, and (b) the association of pre-donation variables with donor recovery. Participants included 273 adult matched unrelated BM (n=131) and PBSC (n=142) donors who donated at U.S. centers between July, 2004 and October, 2009 and completed pre-, 48 hours post-, and weekly post-donation telephone interviews until fully recovered defined as three consecutive symptom-free weeks. Basic socio-demographics, physical and mental health status, and donation-related perceptions were self-reported by donors and key clinical variables were collected from donor centers. Odds-ratios for dichotomous variables and t-tests for continuous variables were used to examine differences in pre- and post-donation variables by donation type and to examine the potential effects of pre-donation variables on recovery at 8-weeks post-donation. Results: At pre-donation, BM donors were significantly more likely to be married (OR=1.82; 1.11–2.94), employed (OR=2.98; 1.05–8.44), and to feel prepared for donation (OR=1.89; 1.01–3.45) than PBSC donors. At 48-hours post-donation, BM donors reported significantly more physical effects of donation including greater intensity (t=3.11; p
Introduction: Although melphalan at a dose of 140 mg/m2 (MEL-140) is known to be an effective pre... more Introduction: Although melphalan at a dose of 140 mg/m2 (MEL-140) is known to be an effective preparative regimen for autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM) patients, there are very few studies comparing it to the most commonly used dose of 200 mg/m2 ( MEL-200). Methods: We retrospectively reviewed the records of all myeloma patients who underwent an ASCT between 2001 and 2010 at our institution. We then identified patients who received melphalan as their preparative regimen at doses of 140 mg/m2 or 200 mg/m2. Patients who received any other drug as conditioning regimen or had more than one ASCT or had documented amyloidosis were excluded. Data were collected for variables known to possibly affect prognosis of MM patients. We assessed effect of melphalan dose on toxicities and outcomes. Results: A total of 129 eligible patients were identified, with 33 receiving MEL-140 and 96 receiving MEL-200. As was expected significantly higher percentage of patients in the MEL-140 arm were older than 65 years (P=<0.001) or had cardiac ejection fraction…
Introduction: The adverse events associated with hematopoietic stem cell donation have been exten... more Introduction: The adverse events associated with hematopoietic stem cell donation have been extensively studied. There is an increasing literature linking psychological factors including stress, anxiety and depression to higher levels of inflammatory burden leading to poorer post-procedural outcomes including longer hospital stays and increased pain perception. Here, we aimed to evaluate whether pre-donation health related quality of life (HRQoL) markers predict toxicity profile and stem cell yield following stem cell donation in healthy donors. Methods: The study population included adult granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cell (PBSC) related donors (RD) (n= 157) and unrelated donors (URD) (n=179) who were enrolled in Related Donor Safety Study (RDSafe) and Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 clinical trials. Pre-donation HR QoL was assessed using the Short-Form (SF-8) in RDSafe and SF-12 questionnaire in BMT CTN 0201 (higher score is better). Pain and toxicity were collected on study specific forms. The primary outcome was the incidence of skeletal pain on day 5 of G-CSF administration. The secondary outcomes were the incidence of skeletal pain and highest toxicity level across selected body symptoms at 1 month, 6 months and 1-year post-donation. Another secondary outcome included CD34+ per liter of blood processed (x10 6/L) on day 5 of G-CSF as a measure of collection yield. The association between pre-apheresis HRQOL measures and pain and acute toxicities was characterized using means and SDs and compared using the t-test. Association between HRQoL and cell yield was assessed using the Pearson correlation coefficient. RD and URD were analyzed separately. Results: URDs were younger than RDs (median age 35 vs. 63). A higher proportion of RDs were female (50% vs. 40%) and obese (41% vs. 35%). A higher proportion of RD PBSC donations required 2 days or more (44% vs 21%). More RDs were collected with lower volume procedures (<18L, 28% vs. 16%), and required a central line (28% vs. 11%). RDs were more likely to report pre-donation grade 1-2 pain (27% vs. 8%) and other toxicities (16% vs. 6%). The mean pre-donation physical component summary (PCS) and mental component summary (MCS) score of RDs were 54.5 (SD 7.0) and 55.1 (SD 5.8), respectively . In the univariate analysis (table 1), pre-donation lower PCS score of RDs was associated with significantly more grade 2-4 pain at 1 month (p=0.0038) and 1-year post-donation (p=0.0099) (Table 1). In multivariable analysis (table 2), pre-donation PCS remained significantly associated with grade 2-4 pain 1-month post-donation (p=0.0098). More specifically, RDs with pre-donation PCS scores in the higher quartile were less likely to experience pain compared with donors with PCS scores in the lower quartile (OR 0.1; 95% CI 0.01-0.83; p=0.005). There was also a trend toward increased grade 2-4 pain at 1-year post-donation among RDs with lower PCS score (p=0.0176). Other outcomes such as pain at day 5 of G-CSF, other toxicities at day 5 of G-CSF, 1 month, 6 months and 1-year post-donation were not associated with pre-donation PCS score. Similarly, there was no significant association between RD pre-donation MCS score and collection-related symptoms at any time point. The mean pre-donation PCS and MCS scores of URDs were 56.2 (SD 4.7) and 54.5 (SD 5.5), respectively . In a univariate analysis, there was no association between PCS score or MCS score and donation associated pain and toxicities at any time point post-donation. Due to low event rates, multivariable analysis was not performed in the URD setting. Based on the multivariable regression analysis, there was no correlation between pre-apheresis HRQoL score (PCS or MSC) and PBSC collection yield in either the RD or URD setting. Conclusion: Our study demonstrates that pre-donation QoL markers are significantly associated with the toxicity profile after PBSC donation in the RD setting as adult RD with lower pre-donation physical QOL experience increased levels of pain after a PBSC collection procedure. There were no such associations found in URD in this small sample. Our findings may help clinicians to identify donors at higher risk of pain with donation, and lead to personalized information and interventions (e.g. increased analgesia) for specific donors. Future study with a larger sample is required to validate the results. Figure 1 Figure 1. Disclosures Farhadfar: Incyte: Consultancy. Stefanski: Novartis: Honoraria. Pulsipher: Equillium: Membership on an entity's Board of Directors or advisory committees; Adaptive: Research Funding; Jasper Therapeutics: Honoraria. Shaw: mallinkrodt: Other: payments; Orca bio: Consultancy.
Abstract 4462 The hematopoietic stem cell transplant comorbidity index (HCT-CI) was developed as ... more Abstract 4462 The hematopoietic stem cell transplant comorbidity index (HCT-CI) was developed as a risk assessment tool in patients undergoing allogeneic HCT. HCT-CI scores have been shown to be associated with non-relapse mortality (NRM) and overall survival (OS) in retrospective studies. However the correlation between HCT-CI scores and post-transplant resource utilization has not been investigated. Previously, we reported a correlation between the HCT-CI and increased hospitalization in the matched related donor setting (Szwed E, et al. Blood. 2010; 116: 4748a). In the unrelated donor population, we retrospectively analyzed 229 consecutive patients who had undergone matched unrelated donor stem cell transplant between January 2001 and December 2008. Donor stem cell sources included peripheral blood (n=90), bone marrow (n=67), and umbilical cord blood (n=72). Conditioning regimens were divided into myeloablative (MA, n = 159), reduced intensity (RIC, n = 28) and non-myeloablative (NMA, n = 42). HCT-CI scores were calculated by method of Sorror (Sorror ML, et al. Blood. 2005 106: 2912–19). Median follow-up was 6.2 years. Consistent with prior findings, HCT-CI correlated with NRM (rs = 0.16, p = 0.015) and overall survival (median survival when score ≤ 3 = 761 days vs score > 3 = 212 days [p = 0.0005]). A negative correlation was found between HCT-CI score and total hospital days as well as days spent in hospital after discharge from initial transplant hospitalization, implying that the higher the score the less time spent in the hospital after transplant (Table 1). However, this correlation disappeared when adjusted for patient survival. We also noted that the majority of readmissions and hospitalizations occurred within the first 100 days from transplant. In subgroup analysis, we found a relationship between HCT-CI score and total hospital days (rs = 0.37, p = 0.0032) and in number of hospital days after discharge for transplant (rs = 0.35, p = 0.0047) for patients who underwent a myeloablative cord blood transplant, even after adjusting for patient survival. In summary, our analysis validated the correlation between HCT-CI score and NRM/overall survival, but we were unable to find a statistically significant correlation between HCT-CI and hospitalizations, except in the myeloablative cord blood setting. We found that most readmissions and hospital days occur early in the post-transplant period (<100 days). We hope further analyses will help unravel these apparent discrepancies in this particular transplant population.Table 1:Spearman Correlation Coefficients between HCT-CI vs. Readmissions and Hospital DaysNMedian Age (yrs)Readmission*Hospital days for Transplant#Admissions after Transplant#Total#Total22935.4−0.002 (0.98)0.0068 (0.92) −0.004 (0.95)−0.26 (<0.0001)0.041 (0.54)−0.16 (0.023)0.11 (0.089)MA−NC9638.9−0.12 (0.24)−0.11 (0.32) −0.17 (0.10)−0.04 (0.68)0.093 (0.36)−0.11 (0.32)0.097 (0.34)MA−C6314.30.11 (0.39)0.093 (0.49) 0.13 (0.32)0.055 (0.67)0.35 (0.0047)0.14 (0.32)0.37 (0.0032)NMA4249.9−0.80 (0.61)−0.32 (0.045) 0.15 (0.35)0.020 (0.90)0.073 (0.65)−0.43 (0.0064)−0.14 (0.39)RIC2847.9−0.10 (0.61)0.18 (0.36)0.011 (0.95)−0.19 (0.35)0.095 (0.63)0.015 (0.94)0.31 (0.11)MA-NC=myeloablative, no cord; MA-C=myeloablative cord; NMA=non-myeloablative; RIC=reduced intensity;() p values in parentheses#Top numbers refer to unadjusted values, bottom are adjusted for patient survival Statistically significant values are bold Disclosures: No relevant conflicts of interest to declare.
Abstract 2023 Background: The role of tandem and salvage autologous stem cell transplant (ASCT) i... more Abstract 2023 Background: The role of tandem and salvage autologous stem cell transplant (ASCT) in multiple myeloma (MM) has been a subject of interest for many myeloma investigators. Further, the role of tandem ASCT in patients achieving very good partial remission (VGPR) or complete remission (CR) has not been studied prospectively. Methods: We conducted a prospective phase II clinical trial in which enrolled MM patients are assessed after the first ASCT. Patients achieving ≤ partial remission (PR) were offered 2nd tandem ASCT followed by maintenance therapy. Patients that were found to be ≥VGPR were offered maintenance therapy followed by salvage ASCT at the time of relapse. Busulfan 0.75 mg/kg PO q 6 hr days -8 through -5, Cyclophosphamide (Cy) 60 mg/kg IV days -3 and -2, and Etoposide 10 mg/kg IV days -4 to -2 were used as the conditioning regimen for the first ASCT. Patients receiving a second ASCT received 96-hour (days -6 to -3) continuous IV Cy 6 gr/m2 and low dose total body irradiation (loTBI) 600 cGy (days -2 and -1). Etoposide was omitted if patients were ≥65 years. Melphalan 140 mg/m2 was used in lieu of TBI if prior irradiation did not allow for TBI. Results: Between the years 2001–2009, 76 patients were enrolled into the study. 54 patients achieved ≥VGPR. 31 patients had ≤ PR and were offered ASCT. Of these patients, 21 patients ultimately received tandem ASCT and 1 patient had tandem autologous-allogeneic transplants. Reasons for not receiving the planned tandem ASCT were lack of socioeconomic resources, physical co-morbidities, and patient refusal. There were no treatment related mortalities in the ASCT patients. Progression-free (PFS) and overall (OS) were compared between the single ASCT (n=54) and tandem ASCT (n=21) groups. The median PFS for the single ASCT group was 27 months (range, 3–107) and 21 months (range, 7–101) in the tandem group (P=0.814). OS was 76 months (range, 5–144) vs. 38 months (range, 12–128), respectively (P=0.121). At the time of submission, a total of 26 (48%) patients in the single ASCT group and 6 (30%) patients in the tandem group are still alive. Among the tandem patients, 2 later underwent salvage ASCT and 3 went on to receive non-myeloablative allogeneic transplants. In the single ASCT group, 6 had salvage ASCT and 7 had allogeneic SCT. All salvage transplants were done at a median of 30 months (range, 8–90) from the last ASCT. Patients who declined tandem transplant had a median PFS of 20 months (range 4–38). Patients who did not quality for tandem ASCT had a median PFS of 28 months (range 3–107) (p–0.08). Median OS between the two groups was 53 months (range 5–95) and 57.5 months (12–144), respectively (p–0.67). Conclusions: Patients who achieve ≥VGPR after 1st ASCT have similar PFS and a trend toward better OS than patients who had tandem ASCT. Thus, the use of such response criteria may identify a group of lower risk patients that will do well without upfront tandem ASCT. Disclosures: No relevant conflicts of interest to declare.
Background Early response to induction therapy for AML assessed by bone marrow (BM) evaluation on... more Background Early response to induction therapy for AML assessed by bone marrow (BM) evaluation on day 14 (D14) post chemotherapy is considered an important predictor of achieving complete remission (CR). Our aim was to identify clinical and laboratory factors influencing the probability of CR in AML patients (pts) with positive D14 BM without receiving further chemotherapy. Methods Records of pts with AML treated between 1998 and 2011 were retrospectively reviewed to identify subjects with positive D14 BM who did not receive re-induction chemotherapy. The distribution of following variables such as age, white blood cell count (WBC) at the time of induction therapy, BM cellularity, percentage of blasts, disease status, and risk was compared by the univariate analysis. Recovery BM status (positive vs. negative for disease) as the response variable and age, WBC at the time of induction therapy, BM cellularity, percentage of blasts, disease status, and risk as explanatory variables were assessed by the logistic regression analysis. Poor risk AML was defined as the presence of adverse karyotype, treatment related disease or presence of antecedent hematologic disorder. Positive BM was defined as either cellularity ≥20% or ≥5% myeloblasts by IHC staining. CR was defined according to IWG 2003 criteria. Results 169/378 (44%) had a positive D14 BM after induction therapy and 92/169 (54%) did not receive re-induction chemotherapy. 68/92 (74%) underwent repeated BM evaluation at WBC recovery, which occurred 4-5 weeks after induction chemotherapy. Recovery BM showed refractory AML in 38/68 (56%) of cases. However, in 30/68 (44%) cases CR was achieved despite previously positive D14 BM. As demonstrated in Table 1, clinical and laboratory characteristics of the CR and refractory groups showed significant differences in the absolute percentage of D14 myeloblasts, abnormal vs. normal myeloblast phenotype, de novo vs. relapse disease status, and risk stratification. Higher blast percentage (P=.0016) was associated with significantly higher probability of having refractory AML and each 1% increase blasts on D14 BM increased the odds of refractory AML on recovery BM by 6% (OR=1.06 95% CI 1.022-1.099) (Figure 1) In contrast, no clear association between D14 BM cellularity and the recovery BM status was found. The results from the multivariate analysis were comparable with that from the univariate analysis. Blast percentage, disease status, and AML risk were strongly and jointly associated with the status of BM recovery. By using a logistic model including myeloblast percentage, myeloblast phenotype, disease status, and AML risk category we correctly predicted 31 refractory AML cases out of 38 (sensitivity = 82%) and we correctly predicted 23 CR cases out of 30 (specificity = 77%). For example, based on our formula, which incorporated blast percentage, disease status, and AML risk we estimated that in a patient with de novo, not a poor risk AML with 5% blasts on D14 BM the probability of positive recovery BM status was 6%, whereas in a patient with relapsed poor risk AML and 50% blasts on D14 BM the probability of positive recovery BM status was 98%. Conclusions Significant proportion of pts with positive D14 BM may achieve CR without subsequent chemotherapy administration. Low blast percentage, absence of phenotypically abnormal myeloblasts, de novo diagnosed AML, and absence of poor risk AML are associated with a significantly higher probability of CR. We developed a useful formula for predicting remission status in the setting of positive D14 BM that would be valuable in clinical trial protocols involving decision trees for re-induction chemotherapy. Disclosures: No relevant conflicts of interest to declare.
Abstract 224 Umbilical cord blood transplantation (UCBT) is an alternative stem cell source for p... more Abstract 224 Umbilical cord blood transplantation (UCBT) is an alternative stem cell source for patients with leukemia in need of an allogeneic transplant without a suitable marrow or peripheral blood stem cell donor. Extensive resources have been mobilized to increase the number of UCB donations from patients of diverse ethnic and racial backgrounds, in an effort to provide an adequate stem cell source for patients of ethnic minorities who may have a difficult time finding a compatible unrelated marrow or peripheral blood stem cell donor. We analyzed the association of race/ethnicity and outcomes of 907 patients receiving unrelated single unit UCBT from 1995 to 2006 for AML, ALL, CML, and MDS and who were reported to the CIBMTR. Race/ethnicity was reported by the transplant centers and included 612 Whites, 145 Blacks and 128 Hispanics. Patients received a variety of conditioning and graft versus host disease (GVHD) prophylaxis regimens. Most patients (72%) received ablative conditioning. Median ages at transplant were 8 years…
Cytomegalovirus (CMV) infection was detected in 65 of 143 (45%) autologous bone marrow transplant... more Cytomegalovirus (CMV) infection was detected in 65 of 143 (45%) autologous bone marrow transplant (BMT) patients. CMV pneumonitis occurred in only 2% of the patients and CMV retinitis occurred in none. Infection occurred in half of the 40 initially seronegative patients and 47% of the 94 initially seropositive patients. Among initially seropositive patients, platelet recovery was slower in infected patients than in those not infected (97 v 35 days median, P = .003), and neutrophil recovery was slightly delayed in infected patients (31 days v 24 days, P = .02). Although the incidence of CMV infection was comparable in autologous and allogeneic BMT patients, CMV pneumonitis was less frequent in autologous BMT patients (2% v 12%, P less than .001). The risk for CMV pneumonitis in autologous BMT patients was comparable with that in allogeneic BMT patients without graft-v-host disease (GVHD) (2% v 6%), but significantly lower than the risk in allogeneic BMT patients with GVHD (2% v 23%, ...
Uploads