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Abstract Absolute lymphocyte count (ALC) post-autologous stem cell transplantation is an independent predictor for survival in Hodgkin’s Disease (HD). Lymphopenia at diagnosis is associated with worse prognosis in patients with newly diagnosed HD. The role of ALC recovery during standard chemotherapy for HD is unknown. We analyzed all patients managed for HD at the Mayo Clinic from 1986 to 2003. Of the 141 consecutive patients, two patients were excluded due to missing ALC data. Of the 139 patients, 63 patients were females and 76 males. The median age of patients at diagnosis was 31 years (range 6–75 years). 118 (85%) patients presented with nodular sclerosis HD, 10 (7%) with mixed cellularity, 2 (1%) with lymphocyte predominance, 1(1%) with lymphocyte depletion, 4 (3%) with lymphocyte predominant (nodular variant), and 4 (3%) unclassified. Frontline chemotherapy included ABVD (N = 79), MOPP-ABV (N = 47), COPP-ABV (N = 8), BEACOPP (N = 3), and Stanford V (N =2). The median number of cycles was 6 (range: 2–10). The median follow-up for the cohort was 62 months (range: 4–221 months). The ALC recovery was analyzed during the first 4 cycles as 90% of the patients received at least 4 cycles of therapy. Patients with an ALC ≥ 1.3 x 109/l at any time point within the first four cycles of chemotherapy (N = 93) demonstrated improved overall survival (OS) and progression-free survival (PFS) compared to patients with an ALC < 1.3 x 109/L at all time points within the first four cycles of chemotherapy (N =46) (10 years OS and PFS: 91% vs 51%, p < 0.0001; 85% vs 52%, p < 0.0001, respectively). Both groups were balanced for the Hasenclever Index: albumin < 4g/dl (p = 0.1), hemoglobin < 10.5 g/dl (p = 0.46), male gender (p =0.21), age ≥ 45 years (p = 0.06), stage IV disease (p = 0.68), leukocytosis ≥ 15 x 109/L (p = 0.58), and lymphopenia < 600 cell/ml (p = 0.211). Multivariate analysis demonstrated ALC recovery to be independent predictor of OS and PFS when compared to the Hasenclever index. These data suggest a critical role of lymphocyte (immune) recovery during standard chemotherapy in HD.

Abstract Background: High dose therapy with autologous stem cell rescue has been shown to prolong survival in patients with multiple myeloma in randomized controlled trials. However, most of the prospective studies have included younger patients, usually 65 or less. It is important to have a better understanding of the outcome of transplantation in the older patients given the median age of onset of myeloma of 65 years. We retrospectively reviewed our institutions experience with high dose therapy for patients over 70 years. Methods: We identified 35 patients with multiple myeloma, from the transplant database, who were at or over the age of 70 at the time of their high dose therapy. We matched these patients to 70 patients (two matches for each patient), based on stage at transplant (primary refractory, plateau phase, relapse off therapy, or relapse on therapy), Durie Salmon stage, high or low labeling index, conventional cytogenetics (abnormal vs normal), presence or absence of circulating plasma cells at time of transplant, and whether cyclophosphamide was used as part of mobilization in that order of priority. Results: The median age of the two groups were 55.3 (Range 37.3–64.8) and 71.7 (Range 70–75.8) years at the time of transplant. The median time to transplant from diagnosis was similar (6.4 for the older patients compared to 6.9 months for the other, P = NS). Ten of the 35 older patients received reduced dose melphalan (140 mg/2)) compared to 3 patients in the control group; P < 0.01. The median follow up from transplant was 10.1 months for the older patients compared to 18 months for the control group. The overall response rate was similar for the two groups (97.1% for the older patients compared to 95.5 for the control group). Eleven (31%) of the older patients and 17 (24%) of the control patients achieved a CR (P = NS). The post transplant progression free survival estimate at 1 year post transplant was 65.3% for the older patients compared to 66% for the control group (P = 0.3)The two year estimated overall survival from transplant was similar in the two groups; 58% for the older patients compared to 67% for the control group. The overall survival from diagnosis was similar for the two groups (P = 0.6). The median number of days hospitalized was 9 days for the older population compared to 5 days for the control group (P = 0.37). Four patients died within the first one hundred days, one (3%) among the older patient group and 3 (4.3%) in the control group. Conclusions: High dose therapy and autologous stem cell transplantation is feasible in selected patients with multiple myeloma over 70 years. It is likely that these older patients were selected based on their overall performance status, a factor that is difficult to analyze in this retrospective review. Nearly 70% of the elderly patients received full dose melphalan for conditioning (200 mg/m2). The toxicity of transplant as well as the outcome appears to be very similar to the younger patients. Patients with multiple myeloma should not be excluded from high dose therapy solely on the basis of their chronological age.

Abstract Intravascular lymphoma is a rare subtype of extranodal DLBCL characterized by the proliferation of malignant B-cells within the lumina of blood vessels. Organ involvement is variable and diffuse. Making the diagnosis can be challenging with symptoms persisting for months prior to definitive diagnosis. Treatment to date with standard anthracycline containing chemotherapy regimens has been disappointing with variable response rates, high relapse rates, and median survival times typically measured in months. We report diagnostic, treatment, and follow-up information regarding a group of patients with intravascular lymphoma evaluated at the Mayo Clinic with special attention to those receiving rituximab and/or high dose chemotherapy with or without peripheral blood autologous stem cell rescue. Methods: The medical records of patients with intravascular lymphoma seen at the Mayo Clinic between January 1970 and May 2005 were reviewed. Patients were included if they had evidence of intravascular lymphoma at the time of diagnosis of lymphoma. Pathologic specimens were reviewed for confirmation of diagnosis. Results: Twenty patients with a diagnosis of intravascular lymphoma were identified. Their median age was 66.5 years. Thirteen (65%) had B symptoms at the time of diagnosis and 13 had a performance status ≥ 3. Nine (45%) had an IPI ≥ 4. The median time to diagnosis from the onset of symptoms was 5.5 months. All had stage IV disease with biopsy proven involvement of at least one organ. The sites of disease involvement were CNS (10), marrow (7), lung (5), adrenal (3), kidney (2), lymph node, seminal vesicle, and skin (1). Two patients had involvement of three organs, six had involvement of two organs, and twelve had involvement of one organ. Nineteen patients received chemotherapy: ProMACE/CytaBOM (3), CHOP (6), RCHOP (6), DHAP (1), high dose methotrexate (1), methylprednisolone, nitrogen mustard, rituximab (1), and hyperCVAD (1). Three patients underwent peripheral blood autologous stem cell rescue after conditioning with BEAM. With a median follow-up of 60 months for all patients, the median overall survival was 8 months. No difference in outcome was seen with regard to site of organ involvement, number of organs involved, presence of B symptoms, or IPI. With a median follow-up for those receiving rituximab of 26 months, the median survival has not yet been reached while the median survival for those receiving non-rituximab containing regimens was 6.5 months. Similarly, with a median follow-up for those receiving high dose chemotherapy (hyperCVAD or BEAM) of 9.3 months, the median survival has not yet been reached while the median survival for those not receiving high dose therapy was 7 months. Conclusion: Intravascular lymphoma is a unique and aggressive subtype of DLBCL. The clinical presentation and sites of organ involvement are variable and the time from onset of symptoms to diagnosis can be prolonged. Standard chemotherapeutic treatment leads to poor outcomes. However, survival may be improved upon with newer strategies such as the use of rituximab and/or high dose chemotherapy with or without peripheral blood autologous stem cell rescue.

Abstract The proposed immune-mediated mechanisms of action of Rituximab (ADCC or “vaccinal” effect) suggest that the efficacy of rituximab therapy depends on the immunocompetency of the host. Therapies, such as IL-12, that stimulate the immune system may increase the efficacy of rituximab. Recently, we reported that absolute lymphocyte count (ALC), as a surrogate maker of immune recovery, is a survival prognostic factor in autologous stem cell transplantation for non-Hodgkin’s lymphoma (NHL). We hypothesize host immune competence (i.e, normal ALC counts) would predict a superior survival in NHL patients treated with rituximab-based regimens. The primary end-point of the study was to assess whether the ALC count prior to rituximab therapy predicted progression-free survival (PFS) and the second end-point was to identify which lymphocyte subset was responsible for affecting PFS. We studied 41 NHL patients that participated in our Phase I interleukin-12 plus rituximab study. These patients were selected because the Phase I study required baseline ALC count and flow cytometry analysis providing lymphocyte subset data prior to treatment. There were 20 females and 21 males in the study. The median age of the cohort was 53 years (range: 34–84). PFS was assessed from the initial date of treatment. The median follow-up was 42 months (1–84 months). Patients with an ALC ≥ 0.9 × 109/l experienced a superior PFS versus an ALC < 0.9 × 109/l prior to rituximab therapy (31 months vs 4 months, p < 0.0001). The relapse rate in the ALC ≥ 0.9 × 109/l group was 55% (11/20) versus 95 % (20/21) in the ALC < 0.9 × 109/l (p < 0.0016). Patients with a CD4 count ≥ 500 cells/μl also experienced a superior PFS versus a CD4 count < 500 cells/μl (21 months vs 9 months, p < 0.0062). The relapse rate in the CD4 count ≥ 500 cells/μl group was 56% (9/16) versus 88 % (22/25) in the CD4 count < 500 cells/μl (p < 0.0216). No association with PFS was identified for CD3, CD8, CD19, CD16/56, the use of IL-12, or lymphoma type by WHO classification. CD4 count was found to be an independent prognostic factor for PFS. In the subgroup of patients with follicular lymphoma, patients with an ALC ≥ 0.9 × 109/l experienced a superior PFS versus an ALC < 0.9 × 109/l prior to rituximab therapy (35 months vs 9 months, p < 0.0076). The relapse rate in the ALC ≥ 0.9 × 109/l group was 45% (5/11) versus 90 % (9/10) in the ALC < 0.9 × 109/l (p < 0.0243). Patients with a CD4 count ≥ 500 cells/μl also experienced superior PFS versus a CD4 count < 500 cells/μl (not reached vs 9 months, p < 0.0098). The relapse rate in the CD4 count ≥ 500 cells/μl group was 29% (2/7) versus 86 % (12/14) in the group with a CD4 count < 500 cells/μl (p < 0.0216). CD4 count was found to be an independent prognostic factor for PFS when compared to the Follicular Lymphoma International Prognostic Index at the time of treatment. Our data suggest the significance of an immunocompetent host in predicting the efficacy of rituximab therapy. These data support our previous report that patients with higher number of activated CD4+ cells at the lymphoma site have a better prognosis (Ansell et al, JCO2001; 19: 720–6). These findings warrant further studies to understand the role of ALC (i.e, CD4 count) in the mechanism of action of rituximab. Supported in part by CA69912

Abstract Rationale Escalation of the Zevalin dose is limited by hematologic toxicity associated with marrow B-cells ± tumor cells. Rituxan treatment before Zevalin may reverse marrow infiltration with malignant and normal B-cells allowing an increase in the dosage of Zevalin with enhanced radiation delivery to lymphoma tumor sites. Since NHL is radiation sensitive, a substantial increase in radiation dose delivered should increase the ORR and CR rates. Design Low-grade follicular/transformed NHL patients receive 4 weekly dose of Rituxan (375mg/m2) before the corresponding Zevalin dose. Bilateral bone marrow biopsies/aspirates as well as biodistribution and dosimetry studies using 111In-2B8 were obtained before and after Rituxan. The trial was schedule to escalate the Zevalin dose (from 0.4 to 0.7 mCi/Kg). After completion of the 0.4 mCi/kg cohort an additional cohort of Rituxan sensitive patients using 0.3 mCi/kg was completed. Safety, pharmacokinetics, dosimetry and preliminary responses are presented. Results 5 pts were enrolled in the 0.4mCi/kg cohort and 6 pts in the 0.3 mCi/kg cohort. In the 10 Rituxan sensitive patients the plasma T ½ and the AUC of 111In-2B8 increased after the administration of Rituxan, with a reduction in the plasma clearance (T½ from 45 ± 4.5 hours to 54 ± 1.9 hours, AUC from 60 ± 10 hrs/μCi/ml to 85 ± 14 hrs/μCi/ml, and the clearance from 1.4 ± 0.3 ml/hrs/kg to 0.9 ± 0.2 ml/hrs/kg). Dosimetry showed no differences in the radiation-absorbed dose for major normal organs (whole body, liver, kidneys) except for the spleen in which a reduction was observed in 7 out of 10 patients. The radiation-absorbed dose to the marrow increased after Rituxan; from 3.6 rads/mCi to 4.28 rads/mCi. In the 0.4 mCi/kg cohort 3 out of 4 evaluable patients for response had a complete response, and 1 patient had progression documented at initial evaluation six weeks post-Zevalin (patient refractory to previous Rituxan). No non-hematological toxicity was observed. One patient had a grade 4 thrombocytopenia, 3 patients had grade 3 thrombocytopenia, and 4 patients had grade 4 WBC and ANC. All patients recovered within two weeks after the nadir. Two out of 6 patients treated in the 0.3 mCi/kg cohort had complete response by physical evaluation, and 4 had partial response; no early progressions were seen in this cohort. No non-hematological toxicity was observed. Only one patient had a grade 4 WBC and ANC, and 2 patients had a grade 3; 3 patients had grade 3 thrombocytopenia; all patients recovered. Conclusions The administration of high doses of Rituxan before Zevalin prolongs the circulation time of the radiolabeled antibody and increases the bone marrow exposure to the radioisotope. Additionally, the increased amount of the radiolabeled antibody available after Rituxan therapy with the prolonged circulation time may explain the unusual high complete response rate observed in this small number of patients despite extensive chemotherapy failures. Although this is very provocative data, the number of patients is very limited to generate a strong conclusion. The trial continues at this time.

Abstract Introduction: We previously reported that serum cardiac biomarkers are among the most powerful predictors of overall survival. This observation was based on outcomes of more than 300 patients with primary systemic amyloidosis (AL) receiving either low dose chemotherapy or high dose chemotherapy with peripheral blood stem cell transplant (PBSCT). Not all institutions use the N-terminal pro-brain natriuretic peptide (NTproBNP) assay, but rather the B-type natriuretic peptide (BNP) assay. We therefore determined the relative utility of BNP in patients with AL undergoing PBSCT and up-dated our results using our NTproBNP-troponin T staging system. Methods: Between 4/10/96 and 2/24/05, 164 patients with AL undergoing PBSCT had measurements of serum cardiac biomarkers. All BNP measurements were done on fresh serum (Biosite Inc., San Diego). The NTproBNP (Roche Diagnostics, Indianapolis, IN) and troponin T (TnT) (Roche Diagnostics, Indianapolis, IN) measurements were done on either stored serum or on fresh samples as previously reported. Follow-up for patients was through March 2005. Results: Between 5/1/03 and 2/15/05, 72 patients had BNP measurements pre-transplant. The median value was 167 pg/ml (range 5 to 7739). Forty-two of these patients also had an NTproBNP measured. There was good agreement between the two tests in the 42 patients that had both measurements (rho 0.823, p<0.0001). To further test the relationship between the two tests, we evaluated the correlation between BNP and NTproBNP using 204 simultaneous measurements from 106 patients (rho=0.89, p<0.0001). Next, we tested the prognostic utility of BNP. Using a cut-off point of 120 pg/L (the upper limit of normal for women over the age of 70 and the 50th percentile of all measurements in our data set), we found that BNP was prognostic for survival post-transplant. It was independent of TnT values, and patients could be divided into 3 risk categories using these two measurements (low risk if both values were low, high-risk if both were high, and intermediate if either was high). This system was highly predictive of overall survival (Figure A). We next compared the BNP-TnT staging system to our previously reported NTproBNP-TnT staging system in the 42 patients that had all 3 values pre-transplant. The correlation between the two staging systems was excellent (rho=0.91, p<0.0001). Follow-up for the 100 patients who had been reported previously is now 26.9 months. As shown in Figure B, the NTproBNP-TnT system predicts for overall survival post transplant. Conclusions: Serum levels of cardiac biomarkers are invaluable prognostic markers in patients with AL. Preliminary data would suggest that a BNP-TnT system is as useful as the NTproBNP-TnT system. Risk thresholds: BNP <120 pg/ml; TnT <0.035 ng/ml; NT-proBNP < 332 pg/ml BNP-TnT statisfaction: low risk, both low; high risk, both high; intermediate, either high. NT-proBNP-TnT satisfaction: low risk, both low; high risk, both high; intermediate, either high. Risk thresholds: BNP <120 pg/ml; TnT <0.035 ng/ml; NT-proBNP < 332 pg/ml BNP-TnT statisfaction: low risk, both low; high risk, both high; intermediate, either high. NT-proBNP-TnT satisfaction: low risk, both low; high risk, both high; intermediate, either high.

Abstract Introduction: The Bone Marrow Transplant Program at Mayo Clinic (Rochester, Minnesota) developed a multidisciplinary approach (involving physicians, nurses, pharmacists, dietitians, and financial specialists) for outpatient management of patients undergoing stem cell transplantation. This approach uses an electronic ordering system for diagnostic tests and chemotherapy to minimize medical errors. Table. Patient Characteristics (N=716) Characteristic Value Male, no. of patients (%) 426 (59) Age, median (IQR), y 59 (53–65) Creatinine, median (IQR), mg/dL 1.0 (0.9–1.2) b2-Microglobulin, median (IQR), mcg/mL 2.5 (1.9–3.7) Gammopathies, no. of patients (%) Measured by serum immunofixation or immunoelectrophoresis IgA 148 (21) IgG 414 (58) IgM 6 (1) IgD 12 (2) Light chain 83 (12) Biclonal 6 (1) None 47 (7) Measured by urine immunofixation or immunoelectrophoresis k light chain 402 (56) l light chain 226 (32) Biclonal 1 (0) None 79 (11) Not performed (anuric) 8 (1) Status at stem cell transplant, no. of patients (%) Untreated 4 (1) Plateau 436 (61) Primary refractory 113 (16) Relapse after therapy 93 (13) Relapse during therapy 70 (10) Characteristic Value CD34+ cells, median (IQR), ×106/kg Collected, no. 10.0 (7.6–12.6) Infused, no. 4.7 (3.9–6.2) Sessions of apheresis, median (IQR) 3 (2–5) Engraftment, median (IQR), days after transplantation Neutrophils, 0.5×109/L 13 (12–15) Platelets, 50×109/L 16 (14–22) Duration of hospitalization, median (IQR), d 4 (0–10) Abbreviation: IQR, interquartile range. Results: During a 45-month period after implementation of the program (2005-Sept 2007), the day-100 survival rate was 99.5% for low-risk myeloma patients (transplantation during first plateau; n=202) and 97% for high-risk myeloma patients (refractory, relapsing or second or greater plateau; n=71). The overall day-100 survival rate was 99%(270/273). Analysis of hospitalization trends since inception of the program showed that 39% of patients completed the transplant procedure as outpatients. The median duration of hospitalization for all patients was 4 days; age and serum creatinine levels were predictive of the need for and duration of hospitalization Conclusion: Outpatient stem cell transplantation is feasible for patients with multiple myeloma with a therapy mortality of 1%. Nearly 40% of our patients completed the procedure without hospitalization. Age and serum creatinine levels predicted a higher likelihood of hospitalization. Implementation of out patient transplant requires affordable housing in the community since many third party payers do not support hotel costs despite the reduction of hospital days. The hospital physical plant and patient registration process has to support use of designated hospital rooms for purely out patient practice. The transplant team must have process owners to standardize across all disease categories collection protocols, conditioning regimens, infusion SOP’s and post infusion supportive care guidelines for standard antibiotics, narcotics, laboratory work and transfusion thresholds. A care team meeting between physicians, nursing, dietary, pharmacy, business office, data base and appointment coordinators is essential to coordinate all the multidisciplinary efforts. Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of age greater than or less than or equal to 65 years Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of age greater than or less than or equal to 65 years Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of creatinine greater than or equal to or less than 1.5mg/dL Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of creatinine greater than or equal to or less than 1.5mg/dL

Abstract The International Prognostic Index at the time of relapse (IPI-R) has been reported to predict clinical outcome in patients with relapsed diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem cell transplantation (ASCT) [Jabbour et al, Leukemia & Lymphoma2005;46(6):861–867; Lerner et al, Biology of Blood and Marrow Transplant2006;13:486–492; and Costa et al, Bone Marrow Transplant2008;41:715–720]. The absolute lymphocyte count (ALC) has been reported as a prognostic factor for survival at diagnosis, during standard chemotherapy and at day 15 post-ASCT for multiple hematological malignancies; however, no reports have addressed whether ALC at the time of relapse (ALC-R) predicts survival. Thus, we assessed the prognostic significance of ALC-R in patients with relapsed DLBCL. To be included in the study, patients were required to have been diagnosed with relapsed DLBCL, have ALC values available from the time of relapse, and to be followed at Mayo Clinic, Rochester. From Feb 2,1987 until March 6, 2006, 121 DLBCL patients qualified for the study. The overall survival (OS) was measured from the time of relapse to the date of death or last follow-up and progression-free survival (PFS) was defined as the time from relapse to the time of progression, relapse, death, or last follow-up. The median age at relapse was 68 years (range:25–88 years) and the median ALC-R was 1.21 x 109/L (range: 0.33–5.99 x 109/L). The value of ALC-R ≥ 1.0 x 109/L was used for the analysis based on previous publications. The groups (ALC-R ≥ 1 or < 1 x 109/L) were balanced for the IPI-R (p=0.1), as well as for undergoing ASCT (p=0.4). Superior OS was observed in patients with an ALC-R ≥ 1.0 x 109/L (N = 76) [median OS: 27.5 months, 3 years OS rates of 42%] compared with patient with an ALC-R < 1.0 x 109/L (N =45) [median OS: 9.4 months, 3 years OS rates of 13%] (p <0.0001). Superior PFS was also observed in patients with an ALC-R ≥ 1.0 x 109/L (N = 76) [median PFS: 14.8 months, 3 years PFS rates of 30%] compared with patient with an ALC-R < 1.0 x 109/L (N =45) [median PFS: 6.2 months, 3 years PFS rates of 11%] (p <0.001). ALC-R was an independent prognostic factor for OS [RR = 0.551, p < 0.009] and PFS [RR = 0.674, p < 0.02] in the multivariate analysis when compared with the IPI-R and whether patients underwent ASCT or not. Our study supports the hypothesis that ALC at relapse predicts clinical outcome in DLBCL and suggests that patient host immunity is an important variable predicting survival in relapsed DLBCL.

Abstract Introduction: We previously reported that plerixafor + G-CSF was as safe as and more effective than placebo + G-CSF in mobilizing hematopoietic stem cell for autologous transplant in patients with non-Hodgkins lymphoma (NHL) through 100 days follow-up (DiPersio ASH 2007). We report herein the 12 months data. Methods: This was a phase 3, multicenter, randomized, double-blind, placebo-controlled study. NHL patients requiring an autologous hematopoietic stem cell transplant were eligible. Patients received G-CSF (10 μg/kg) subcutaneously daily for up to 8 days. Beginning on evening of Day 4 and continuing daily for up to 4 days, patients received either plerixafor (240 μg/kg) or placebo subcutaneously. Starting on morning of Day 5, patients began daily apheresis for up to 4 days or until ≥ 5 x 106 CD34+cells/kg were collected. We report herein the 12 months graft durability and hematology data. Results: As reported previously, 89/150 (59%) patients in the plerixafor group and 29/148 (20%) patients in the placebo group met the primary endpoint of collecting ≥ 5 x 106 CD34+ cells/kg in ≤ 4 days of apheresis, p < 0.001. 135 patients (90%) in plerixafor group and 82 patients (55%) in placebo group underwent transplantation. Median time to neutrophil and platelet engraftment was similar in both groups. There were no differences in graft durability through 12 months follow-up between the two groups. Two plerixa for treated patients had graft failure (one had pre-existing MDS and one developed AML). One plerixafor-treated patient had delayed platelet engraftment. The hematology profiles were similar between the two groups through 12 months follow-up, except that patients in the plerixafor group had significantly higher platelet count at 12 months than patients in the placebo group (p=0.026) (Table 1). During the 12 months follow-up, 14/135 (10.4%) patients in plerixafor group and 10/82 (12.2%) patients in the placebo group died. 7/14 in the plerixafor group and 5/10 in the placebo group died of disease progression. Plerixafor + G-CSF Placebo + G-CSF Hematology data presented as mean ± SD and n= number of patients with available data aAll patients who underwent transplantation bAll patients who underwent transplantation and had laboratory data at the study visit cP values were NS for all variables at all time points between groups except for platelet count at 12 months (p=0.026) Graft durability (n, %) 100 daysa 128/135 (94.8%) 78/82 (95.1%) 6 monthsb 120/123 (97.6%) 77/78 (98.7%) 12 monthsb 110/112 (98.2%) 65/65 (100.0%) Platelet (x 109/L) 100 days 183 ± 83 (n= 113) 169 ± 81 (n=63) 6 months 190 ± 78 (n=100) 180 ± 77 (n=64) 12 monthsc 209 ± 81 (n=50) 170 ± 78 (n=37) Neutrophils (x 109/L) 100 days 3.1 ± 1.7 (n=107) 3.2 ± 2.1 (n=61) 6 months 3.3 ± 1.4 (n=98) 3.8 ± 2.6 (n=64) 12 months 3.5 ± 1.4 (n=50) 4.2 ± 2.7 (n=38) Hemogloblin (mg/dL) 100 days 12.3 ± 1.5 (n=112) 12.3 ± 1.5 (n=63) 6 months 12.5 ± 1.5 (n=100) 12.4 ± 1.5 (n=64) 12 months 13.0 ± 1.4 (n=50) 12.7 ± 1.6 (n=37) Conclusions: The addition of plerixafor to G-CSF resulted in higher CD34+ cell collection in fewer days of apheresis and higher proportion of patients proceeding to transplant than G-CSF alone. Importantly, this 12 months report showed that transplants with cells collected with plerixafor resulted in graft durability rates that were similar to cells collected with G-CSF alone.

Abstract Background: Germinal center B cell-like (GCB) DLBCL, as determined by gene expression profiling or immunohistochemistry, is more likely to be cured by initial conventional chemoimmunotherapy than non-germinal center B cell-like (non-GCB) DLBCL. For patients with relapsed or refractory chemosensitive DLBCL, high-dose chemotherapy and autologous hematopoietic stem cell (HSC) transplant is considered standard-of-care treatment, but it is unknown whether the outcome of these patients is similarly influenced by the subtype of DLBCL. We therefore explored the differences between patients with GCB and non-GCB DLBCL as regards their clinical features at relapse after first line therapy and their outcome following salvage autologous HSC transplant. Methods: Patients undergoing BEAM conditioning and autologous HSC transplantation for relapsed or refractory chemosensitive DLBCL at Mayo Clinic, Rochester, MN between 2001 and 2006 were included. Immunohistochemical analysis was performed for CD10, BCL-6 and MUM1 allowing classification in GCB and non-GCB-like DLBCL, as well as for BCL-2. GCB and non-GCB groups were compared in terms of known prognostic factors at time of progression and outcome after HSC transplant Results: Fifty-nine patients were included and had retrievable tumor samples to allow immunohistochemical analysis. Median follow-up of survivors was 25 months; median age at the time of transplant was 60 years (range 17–77); All patients had failed at least one previous anthracycline-based regimen (15 had refractory disease). Overall, 25/59 cases (42%) were positive for CD10, 32/58 (55%) for BCL-6, and 19/58 (32%) for MUM1. Thirty-two patients (54%) were classified as having GCB and 27 (46%) non-GCB-like DLBCL. Patients in the GCB and non-GCB group had similar time to progression (TTP) (median 12.5 months vs. 11 months, Wilcoxon P=0.81) after first line therapy and similar IPI-R scores (Chi-square, P=0.38). In univariate analysis, GCB and non-GCB did not differ in time to relapse after HSC transplant (log rank test P=0.77) or survival (log rank test P=0.48; figure). The lack of demonstrable difference in survival persisted even after correction for IPI-R and TTP, factors know to affect transplant outcome (Cox regression, RR=0.80 for GCB; P=0.28). BCL-2 was highly expressed in both GCB (81%) and non-GCB (96%) and did not correlate with outcome in the entire population nor in any of the two groups. Conclusion: Patients with chemosensitive relapsed or refractory GCB and non-GCB-like DLBCL derive similar benefit from autologous HSC transplant. Figure Figure