Litzow, Mark R.

Abstract Over the past decade several prospective studies of post-remission therapy in AML have compared allogeneic hematopoietic stem cell transplantation (HSCT), autologous HSCT and chemotherapy. The data are appropriately presented by intention-to-treat analyses. However, such analyses do not provide information to the clinician or patient as to outcome from the initiation of post-remission therapy, be it HSCT or chemotherapy. Furthermore, such analyses are impossible to interpret when a significant percentage of patients do not receive their intended therapies (for example, only 54% of patients randomized to autologous HSCT; Cassileth, NEJM, 1998). Finally, such studies present survival data that may not be relevant to current practice where the mortality from autologous HSCT has decreased sharply (for example, 14% non-relapse mortality from autologous HSCT; Cassileth, NEJM, 1998). In the current analysis, results from 4 consecutive ECOG studies that included autologous HSCT were analyzed and the data collated. In PC486 patients received standard induction followed by allogeneic HSCT if they had a compatible sibling; otherwise they were to undergo an autologous HSCT without any prior consolidation (Cassileth, JCO, 1993). E4995 studied standard induction with added high-dose cytarabine (HiDAC) intensification on D 8–10, followed by 2 courses of HiDAC consolidation. All patients were to undergo an autologous HSCT after induction and consolidation (Cassileth, Leuk Lymph, 2005). E3489 was a US Intergroup study in which patients received standard induction (3 + 7). If in CR, all patients received an attenuated course of induction (2 + 5). Patients who had a histocompatible sibling were assigned to allogeneic HSCT; those without a donor were randomized to an autologous HSCT or chemotherapy (Cassileth, NEJM, 1998). E1900 is an ongoing phase III study in which patients receive standard induction followed by allogeneic HSCT or two courses of HiDAC followed by autologous HSCT. The latter study is ongoing; therefore, only data describing transplant-related mortality (TRM) are presented. The relapse rate from start of each post-remission regimen in these studies, based on therapy actually received and not on intention-to-treat analysis, is presented in table 1 and the TRM is presented in table 2. Table 1. Relapse Rate from Start of Post-Remission Therapy Cytogenetics Allogeneic HSCT (n=85) Autologous HSCT (n=113) Chemotherapy (n=109) Favorable 11.8% (2/17) 10.5% (2/19) 60% (12/20) Intermediate 20.5% (8/39) 32.3% (10/31) 53.7% (22/41) Unfavorable 16.7% (2/12) 41.7% (5/12) 83.3% (15/18) Unknown 23.5% (4/17) 33.3% (17/51) 56.7% (17/30) Table 2. Treatment-Related Mortality after Post-Remission Therapy Allogeneic HSCT Autologous HSCT – Marrow Autologous HSCT – Blood Chemotherapy Study E3489, E4995, E1900 E3489, PC 486 E4995, E1900 E3489 Treatment-related mortality 15.3% (18/117) 11% (16/85) 1.5% (2/135) 2.7% (3/109) In conclusion: The TRM after autologous HSCT using mobilized peripheral blood has decreased substantially in recent years. As shown in table 2, in PC486 and E3489 where bone marrow was harvested and treated with perfosfamide (4-HC) prior to cryo-preservation, the TRM was significantly greater than in the later studies, E4995 and E1900, where peripheral blood was harvested after priming with chemotherapy and/or cytokines. The lower relapse rate post autologous transplant, together with the lower procedural mortality with current practice, may confer a survival advantage in future prospective studies of autologous HSCT versus chemotherapy. While absolute comparisons cannot be made, as the timing of each therapy may not be identical, these data provide crucial information for informed and patient/physician discussions prior to initiation of postremission therapy.

Abstract Background: Myelofibrosis (MF) shortens survival but also compromises quality of life from disease associated splenomegaly and constitutional symptoms (fatigue, weight loss, night sweats, and bone pain). No current validated instrument of patient reported outcomes (PRO) captures the spectrum of MF associated symptoms. In an era of rapid development and testing of therapeutic agents which may impact the natural history and symptoms associated with MF (such as JAK2 inhibitors) a uniform and validated instrument for capturing the presence, severity (and potentially improvement) of MF symptoms is needed. We sought to develop and validate such an instrument, the myelofibrosis symptom assessment form (MFSAF). Methods: Based upon the results in our MF QOL survey (Cancer2007;109(1):68–76), we developed the MFSAF to assess fatigue (via the brief fatigue inventory (BFI-Cancer1999;85:1186)), additional symptoms were independently assessed for presence and severity on a scale from 0 (absent) to 10 (worst possible) for splenomegaly associated symptoms (early satiety, pain, inactivity, cough) night sweats, itching, bone pain, fever, unintentional weight loss as well as an estimate of overall quality of life. Additionally, patients provided feedback on the quality and nature of the MFSAF, and also completed for comparison validated instruments including the Memorial Symptom Assessment Scale (MSAS), the Insomnia Severity Index (ISI), and the Brief Pain Index. Physician input was included including their assessment of patient’s fatigue, spleen symptoms, and quality of life (blinded to patient’s responses) as well as clinical history, lab and exam findings. Results: MFSAF Results 34 MPD patients were enrolled (24 MF, 10 in the comparison group (4 polycythemia vera (PV), 6 essential thrombocythemia (ET)). the MFSAF was rated by patients as easy to understand (median score 1, range 0–6), and “addressed most of my symptoms” (median score 1, range 0–6) both on a scale of 0 (as good as possible to 10 as bad as possible). When asked if a symptom was not addressed (open ended response) no single symptom was named more than once. As we have previously reported fatigue was common with BFI scores (median 3.6 (0–10) for MF and 2.5 (range 0.2–3.8) for the ET/PV group (increasing BFI score associated with worsening fatigue) worse than median score of published “healthy” controls 2.2. Additional MF associated symptoms were captured well by the MFSAF with splenic, constitutional symptoms, and QOL (median 3 (range 0–7) MF, median 2 (0–3) ET/PV) documented easily and worse than ET/PV controls. Physicians estimation of QOL was excellent (median 3 (0–8) for MF, median 2 (0–4) for ET/PV). MFSAF Comparison to other Instruments: The MSAS demonstrated more adverse values for MF (than ET/PV) in the PSYCH (psychologic stress; mean-1.27 (STD DEV 0.80), PHYS (physical symptoms; mean 0.90 (STD DEV 0.53)), GDI (Global Distress Index mean-1.29 (STD DEV 0.77)) and a total MSAS symptom score (mean 0.85 (std dev (0.49)) comparable with advanced renal disease (PSYCH 0.99, PHYS 0.99, GDI 1.27, and MSAS of 0.81; J of Pall Med2007;10(6):1266), as well as advanced lung disease, AIDS, and various advanced malignancies. Individual, previously validated MSAS questions were all highly correlated (all p<0.01) with MFSAF (in italic) counterparts including lack of energy (fatigue), cough (same), pain (both abdominal pain and bone pain), sweats (night sweats), itching (same), and weight loss (same). Further validation of pain measurements in the MFSAF came from comparison to the BPI where both individually the presence, and intensity of pain (both abdominal and bone) were highly correlated (all p<0.01). Insomnia, not yet included in the MFSAF, was present in 68% and 63% of patients (MSAS and ISI, respectively). Additionally, problems with sexual interest, or activity, was noted in 35% of patients to the MSAS. Conclusions: Currently available instruments of PRO and symptoms are lengthy, and individually incomplete for assessing the presence and severity of the diverse nature of symptoms associated with MF. The proposed MFSAF, was comprehensive and well understood by patients and the results for the individual symptoms assessed were highly correlated with previously validated instruments for other conditions as well as with physicians perceptions of fatigue and QOL. The MFSAF, with the addition of questions regarding insomnia and sexuality, should be utilized in all trials of therapeutic agents in MF patients in which symptomatic improvements are an endpoint.

Abstract Introduction: We retrospectively analyzed outcomes of 716 patients with multiple myeloma who were mobilized using cyclophosphamide and growth factor (n=370) or growth factor alone (n=346) before stem cell transplantation. Table. Patient Characteristics (N=716) Variable Cyclophosphamide (n=370) Growth Factor Only (n=346) P Value Abbreviation: IQR, interquartile range. *Or equivalent dosage. Men, No. of patients (%) 224 (61) 202 (58) .50 Age, median (IQR), y 58 (52–64) 60 (53–65) .11 b-2 Microglobulin, median (IQR), mcg/mL 2.7 (1.9–4.0) 2.3 (1.9–3.2) .01 Creatinine, median (IQR), mg/dL 1.1 (0.9–1.3) 1.0 (0.8–1.2) .002 Apheresis, median (IQR) collections, No. 2 (1–3) 4 (3–6) .001 Marrow plasma cells, % 17 (5–34) 5 (1–13) .001 CD34+cells, median (IQR), cells/kg Total collected 10.3x106(7.2x106–14.6x106) 9.9x106(7.6x106–11.9x106) .01 Infused 5.6x106(4.5x106–7.6x106) 4.2x106(3.8x106–5.0x106) <.001 Duration of hospitalization, median (IQR), d 4 (0–10) 4 (0–9) .92 Nonstaphylococcal bacteremia, No. of patients (%) 48 (13) 25 (7) .01 Melphalan dosage, No. of patients (%) .04 200 mg/m2* 337 (91) 298 (86) 140 mg/m2* 33 (9) 48 (14) Exposure before mobilization, No. of patients (%) Melphalan 45 (12) 44 (13) .50 Lenalidomide 14(4) 63(18) .01 Results: Patients receiving cyclophosphamide had higher stem cell yields than the growth factor only group (median number of apheresis sessions needed to achieve stem cell collection goals, 2 vs 4 sessions, respectively [P=.001]). However, patients treated with cyclophosphamide required more time for engraftment of platelets and neutrophils (P<.001 for both). For patients receiving cyclophosphamide, 75% achieved engraftment (defined as a platelet count of 50x109/L) by day 39, whereas 75% of patients not receiving cyclophosphamide achieved engraftment by day 18. Similar results were observed for neutrophil engraftment. These differences did not affect the duration of hospitalization, but patients treated with cyclophosphamide had a higher incidence of posttransplant nonstaphylococcal bacteremia. For cyclophosphamide-mobilized patients, considerably faster platelet engraftment (5 fewer days) resulted if stem cell reinfusion occurred more than 30 days after the first apheresis session. Conclusion: Our data suggested that cyclophosphamide damaged the microenvironment and slowed engraftment. By lengthening the period between the completion of apheresis and stem cell reinfusion, the microenvironment may recover and result in faster engraftment. We suggest that the cyclophosphamide used for mobilization may affect the marrow microenvironment. Cyclophosphamide improves yields but increases bacteremia rates after transplantation. Cyclophosphamide increases time required to collect stem cells and slows engraftment. Figure Figure

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

Abstract Results from clinical trials may change with time. Data presented in initial abstracts or early reports are often different from what appears in subsequent publications, sometimes due to a more rigorous analysis (as in initial response rates) or to maturity of data (as in reports of survival). Survival curves usually provide projected data based on Kaplan-Meier analyses. Such data may change with time when unexpected events occur (as, for example, relapse after T-cell depleted allogeneic transplants) or more patients advance to the initially projected time point. For AML, several groups have reported that there are very few relapses beyond 3 years. At issue is the optimal time for reporting these survival data. Table 1 reports data from 6 consecutive clinical trials addressing induction and post-remission questions in AML patients performed by ECOG. These data compare the 3-year overall survival (OS) and disease-free survival (DFS) for the identical cohorts of patients as presented at 1 year and at 3 years after completion of the study accrual. PC 486 was a phase II study of induction therapy followed by allogeneic or autologous transplant without prior consolidation. E 3489 was a US intergroup study in which patients received post-induction therapy using an allogeneic transplant (allo), an autologous transplant (auto) or chemotherapy (chemo). E1490 was a study in older adults of induction and consolidation with GM-CSF or placebo. E2491 was an intergroup study comparing ATRA induction versus standard chemotherapy in patients with APL. After consolidation, patients were randomized to maintenance with ATRA versus observation (obs). E3993 was a study in older adults comparing priming with GMCSF or placebo. E4995 was a phase II study of intensified induction and consolidation followed by an autologous transplant. For the same cohorts of patients the 3-year OS tends to decrease as the time from completion of study accrual increases. When looking at the DFS, while a decrease may also occur, in several studies there was an improved DFS with time (for example, in E2491, chemo to ATRA, or in E3993 with GM-CSF priming). There were no changes in either OS or DFS beyond 3 years (data not shown). Table 1: Three-year OS and DFS Presented at Different Time Points OS (%) DFS (%) Study One year Three years One year Three years PC 486 auto or allo HSCT 42 → 38 45 → 39 E 3489 allo HSCT 50 → 50 48 → 47 auto HSCT 47 → 46 39 → 39 chemo 56 → 51 36 → 36 E 1490 Induction / consolidation GM-CSF 23 → 22 23 → 24 placebo 15 → 12 16 → 15 E2491 APL induction+ maintenance ATRA + ATRA 87 → 84 72 → 73 ATRA + obs 83 → 80 61 → 60 chemo + ATRA 81 → 75 43 → 58 chemo + obs 54 → 45 16 → 18 E 3993 Induction/consolidation GM-CSF priming 13 → 11 5 → 10 placebo 14 → 14 9 → 9 E 4995 Induction / consolidation / auto HSCT 54 → 48 63 → 53 In conclusion: For large cooperative group studies, treatment results in AML presented one year from conclusion of study accrual are unlikely to dramatically alter the overall results. Nonetheless, some differences may occur, both in OS and DFS, warranting caution in interpreting the data and comparing with other published reports. Such differences are likely to be even greater if data are presented upon completion of study accrual, prior to one year - although, in a cooperative group setting, this should be balanced against the need to release data for future planning. Publication of interim data, before conclusion of the study accrual, may be misleading and are to be strongly discouraged. Three years appear to be the appropriate time for the publication of definitive survival data.

Abstract This phase 1 clinical trial evaluated the safety and effects of autologous dendritic cells (DC) injected to patients in late chronic or accelerated phase of chronic myelogenous leukemia (CML). Seven patients with a median age of 63 years (range 55–78) entered the trial. Median time from diagnosis to registration was 38 months (range 16–94). Two patients were in the accelerated phase of disease based on the presence of additional bone marrow chromosomal abnormalities, all other patients were in chronic phase. Prior therapies included hydroxyurea and alpha interferon with or without cytosine arabinoside. Four patients were on therapy with imatinib mesylate during the course of the trial, two were treated before imatinib became available and one was previously intolerant of imatinib. CD14+ monocytes were selected from a leukapheresis product by clinical grade immunoadsorption (Miltenyi Biotec). The monocytes were matured to CD83+ and bcr-abl+ DC after 10 days in culture with X-VIVO 15 medium with 1% human AB serum, GM-CSF, IL-4, as the base culture media followed by maturation mediated by TNF-alpha, IL-6 and prostaglandin E2. The first patient entered had a positive mycoplasma reaction by polymerase chain reaction at the time of his first DC injection, the cells were not given and he was withdrawn from the study. The other six patients were treated in two cohorts of three patients and received four injections each of 3x106 DC and 15x106 DC per injection, respectively. CML-DC injections were generally well tolerated and all non-hematologic toxicities were ≤ grade 2. All injections were given intra-nodally into a cervical lymph node except in the first patient where the DCs were injected subcutaneously. We observed no major clinical responses, but the white blood cell counts normalized or were maintained at normal level in four patients during therapy. Three patients experienced a transient reduction in the percentage of bcr-abl+ cells suggesting that the treatment may have affected the cells in a leukemia specific manner. We detected vascular endothelial growth factor (VEGF) in the plasma prior to therapy. In four of five patients, VEGF levels decreased by more than 75 percent during therapy. T cells isolated from patients’ blood and incubated with autologous CML DC before, during and after therapy showed increased proliferation and secretion of interferon gamma during the course of therapy. DCs from three patients were transfected with a recombinant replication-defective adenovirus carrying the gene for IL-2 under a constitutively active promoter. IL-2 secreted by transfected dendritic cells enhanced in vitro T cell proliferation and interferon gamma release and these effects increased with increasing numbers of DC injections. This study demonstrates that CML-DC can be prepared from the blood of patients treated with imatinib mesylate, that they can be administered safely and that progress of therapy is accompanied by an increase in DC-specific T cell reactivity and a decrease in circulating VEGF.

Abstract Background: In childhood acute lymphoblastic leukemia (ALL), a rapid decline of circulating blasts in response to induction chemotherapy or prednisone is one of the most important prognostic factors for achieving remission and for relapse-free survival (RFS). However, in AML parameters of chemosensitivity have been restricted to the assessment of residual bone marrow (BM) blasts during aplasia. We hypothesized that time to peripheral blood (PB) blast clearance would have prognostic relevance with respect to RFS in AML. Methods: From 1994 to 2006 outcomes of 86 adults (47 males; median age 52 y) with previously untreated AML (non- acute promyelocytic leukemia) achieving CR and receiving high-dose cytarabine (HDAC)-based consolidation have been included in this retrospective analysis. The median and range of white blood cell count (WBC), platelet count and PB blast percent were 5.3 × 109/L (0.9–267), 59 ×109/L (5–361) 22.5% (0–97), respectively. A 100 cell manual slide differential count was done in all with PB blasts unless the WBC was less than 0.5 ×109/L. Karyotype was classified as favorable, intermediate and unfavorable in 10, 63 and 12 cases, respectively and failed in one. Induction consisted of idarubicin at 12 mg/m2/ d (n=70) or daunorubicin at 45 mg/m2/d (n=16) on days 1–3 with infusional cytarabine at 100 mg/m2/ d on days 1–7 and repeated in those with persistent BM blasts on day 14 (n=17). The first consolidation was the same as that used to achieve CR. Thereafter, 3 courses of HDAC at 3g/m2 (1.5 g/m2 if ≥ 60 y) q12 h on days 1, 3 and 5 were planned. Results: At the time of analyses, 43% had died, primarily of relapse (97%). Median overall survival (OS) and RFS were 30.2 m (5.5–133) and 14 m (2–131.5), respectively. The median time to PB blast clearance was five days (range: 2–10). For this analysis, only those with PB blasts at initiation of induction (n=73) were included. We defined the day of PB blast clearance as the first day after commencing induction that PB blasts were absent. Separation according to blast clearance on or before day 5 resulted in the most balanced distribution and strongest significant difference between each subgroup of 45 and 28 patients, with significantly different rates of relapse of 33% and 79%, respectively (p<0.0001). We also defined three “blast risk groups” as good, intermediate and poor, according to PB blast clearance on or before day 3, on days 4 or 5, or on day 6 or beyond, respectively. This provided 3 well-balanced groups (good, intermediate and poor) of 16, 30 and 27 patients with significantly different and escalating relapse rates of 12.5%, 47% and 78%, respectively (Fig 1). Univariate analysis of several variables identified PB blast clearance day (p<0.0001), number of inductions to CR (p =0.0043) and cytogenetic risk group (p=0.028) as being significantly associated with RFS. On multivariable analysis, only the first sustained its significance. The results were similar for OS. Conclusion: In adults who achieve CR after induction chemotherapy for non-APL AML, early PB blast clearance predicts superior RFS and OS. Figure Figure

Abstract INTRODUCTION The bone marrow plasma cell labeling index (PCLI) and the beta 2 microglobulin (β2M) when combined provide a powerful staging system highly predictive of outcomes in myeloma patients (Greipp et. al., Blood, 81:3382–87, 1993). This staging system lacks information on cytogenetics and it has been demonstrated that deletion 13 (Δ13) by conventional cytogenetics is associated with poor outcomes. In conventionally treated patients Δ13 by FISH is an independent prognostic variable. We analyzed the importance of Δ13 by FISH in a cohort of patients receiving high dose therapy and assessed its value relative to known prognostic parameters, PCLI and β2M. PATIENTS AND METHODS 238 patients undergoing high dose therapy between January 1990 and September 2001 were studied. The minimum follow-up of patients was 34 months. The median age of the cohort 56 years. Interphase fluorescence in situ hybridization with Probes LSI13/D13S319 was performed with simultaneous immunofluorescent detection of bone marrow plasma cells by the presence of cytoplasmic immunoglobulin. PCLI was done by a slide-based immunofluorescence method with antibodies to bromodeoxyuridine. RESULTS Of the 238 patients studied 215 had a successful FISH analysis and 212 of these had a bone marrow labeling index. Deletion 13 was absent in 104 patients (48%) and present in 111 patients. The overall survival and time to progression for patients lacking and having deletion 13 was 47.8 vs 26.4 (OS) and 19.0 vs 11.7 (TTP)months respectively. A Cox model was constructed with the PCLI, the presence or absence of deletion 13 and serum β2M. Although all three variables were independently predictive of survival and time to progression, the β2M was the weakest of these three variables. The hazard function for survival for PCLI, deletion 13 and β2M was 1.4, 1.6 and 1.1 respectively. A staging system was constructed assigning 1 point for the presence of deletion 13 or a PCLI ≥ 1%. Patients fell into 3 categories of 0 points (N=69), 1 point (N=104) and 2 points (N=39). The overall survival for the three groups respectively were 56.5, 36.6 and 13.7 months (figure). The time to progression for the three groups were 22.3, 15.4 and 8 months (P<0.001). When analysis was limited to those patients transplanted within 12 months of diagnosis the results remained significant (P<0.003) with median survivals of stage 0, 1 and 2 of 72.5, 59.1 and 15.4 months respectively. TTP for stage 0, 1 & 2 in this same cohort of patients transplanted < 12 mos after diagnosis is 30.6, 21.5 & 8.2 months respectively. CONCLUSION Deletion 13 by FISH is an independent predictor of survival and time to progression providing information independent of the β2M and the PCLI. Combining the PCLI with FISH del 13 identifies patients who following transplant have a median time to progression of 8 months and a median OS of 13.7 months. This group may not benefit from autologous transplant and are candidates for novel therapeutic approaches. Figure Figure

Abstract The infused autograft absolute lymphocyte count (A-ALC) is an independent prognostic factor for survival after autologous hematopoietic stem cell transplant (AHSCT) in non-Hodgkin’s lymphoma (NHL). Previous studies have shown that A-ALC directly correlates with the peripheral blood absolute lymphocyte count (PC-ALC) at the time of apheresis collection. However, factors affecting the PC-ALC at apheresis remain undefined. We hypothesized that one possible factor impacting PC-ALC may be the time interval from last chemotherapy to stem cell collection (TILC). Data from 160 patients who underwent AHSCT for treatment of relapsed NHL at Mayo Clinic between 1993 and 2001 were collected and analyzed. The primary end point of this study was correlation between TILC and PC-ALC, and our analysis revealed a strong correlation (r = 0.67, p < 0.0001). Further analysis revealed higher PC-ALC numbers in patients with TILC ≥ 60 days versus TILC < 60 days (median of 7.44 x 109/L in the ≥ 60 day group versus 3.87 x 109/L in the < 60 day group, p < 0.0001). Both the median overall survival (figure below) and the progression-free survival were longer in the TILC ≥ 60 days group versus the TILC < 60 days group (76 versus 21 months, p < 0.0037; 76 versus 11 months, p < 0.018, respectively). These findings were independent of other prognostic indicators for relapsed NHL patients undergoing APHSCT. The data supports our hypothesis that TILC affects PC-ALC and survival post-AHSCT in NHL. Figure Figure