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Introduction: Transformation of low grade follicular lymphoma (FL) to diffuse large B cell lymphoma (DLBCL) carries a poor prognosis. In retrospective studies, 5-year survival of transformed DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) without autologous stem cell transplant is 40-60%, underscoring need to improve frontline treatment of transformed DLBCL beyond R-CHOP. The overall response rate (ORR) to lenalidomide used as a single agent for relapsed transformed non Hodgkin lymphoma was 45% with 21% complete response (CR) rate and a median duration of response of 12 months (Witzig et al, Ann Onc 2011). These data provided the rationale to include patients with transformed DLBCL (with historical and concurrent FL) in MC078E, a phase II clinical trial testing lenalidomide plus R-CHOP (R2CHOP) for patients with new and untreated de novo and transformed DLBCL (NCT00670358). Here we present analysis of the subset of transformed DLBCL patients. Methods: Adult patients with transformed DLBCL and either historical or concurrent FL, stage >=2, measurable disease by Positron Emission Tomography/computed tomography (PET/CT) and adequate organ function were included. Patients with Central Nervous System (CNS) involvement, significant comorbidities, active non-lymphomatous malignancy, life-threatening thromboembolism (TE) and contraindication to aspirin prophylaxis were excluded. Study participants received up to 6 cycles of rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1.4 mg /m2) on day 1, prednisone (100 mg) on day 1-5, pegfilgrastim on day 2, and Lenalidomide 25 mg day 1-10 of 21 day cycle. Tumor lysis prophylaxis was per local practice; patients also received TE prophylaxis with aspirin. Primary outcome was event free survival (EFS) at 12 months, where an event was defined as death, progression or subsequent anti-lymphoma therapy. Secondary outcomes included ORR, CR, progression free survival (PFS), and overall survival (OS). Response was evaluated by PET/CT after cycle 2 and cycle 6 with revised response criteria (Cheson et al, 2007). Adverse events were recorded according to CTCAE version 3.0. The Kaplan-Meier method was used to estimate time to event endpoints. Results: Thirty-nine patients were accrued from August 5, 2013 to July 28, 2020 and 33 were eligible by central pathology review. Median age was 64 (range 24-80) years and 18 (54%) were >60 years old. Eighteen (54%) were male, and 32 (97%) had ECOG performance status <2. Twenty-three (70%) had historical FL and 10 (30%) had concurrent FL. Twenty-six (79%) had advanced stage (III-IV). Median number of extra nodal sites were 1 (0-4). Thirteen (39%) had high international prognostic index (IPI) (4-5). Thirty-two (97%) completed at least 2 cycles (30 completed all 6 cycles) and were evaluable for response. ORR was 97% (32/33), 29 (88%) had CR and 3 had PR. EFS at 12 months was 87.9% (95% CI: 71.8, 96.6). Two-year PFS and OS were 84.5% (95% CI: 72.8%-98%) and 96.9% (95% CI: 91-100%) (Figure 1). Twenty nine completed study protocol, 4 discontinued protocol early for disease progression (1), adverse event (AE) (1), refusal (1) and noncompliance (1). Thirty (91%) had hematologic AE of grade 3 or above, 27 (82%) had neutropenia, 16 (48%) had thrombocytopenia, and 7 (21%) had anemia. Sixteen (48%) had grade 3 or above non-hematologic AE. Eight (24%) had febrile neutropenia. There were 3 deaths on this study, 1 due to progressive DLBCL, 1 due to AML and 1 due to malignant melanoma. Conclusion: R2CHOP appears effective in transformed DLBCL with high response rates, event free, progression free and overall survival seen in current study. This study supports the inclusion of anthracycline naive patients with transformed DLBCL in future randomized studies of lenalidomide or other novel immunomodulatory (IMiD) analogues. Disclosures Wang: Novartis: Research Funding; Innocare: Research Funding; Incyte: Research Funding. Ansell:Bristol Myers Squibb: Research Funding; Takeda: Research Funding; AI Therapeutics: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; ADC Therapeutics: Research Funding. Witzig:Spectrum: Consultancy; Immune Design: Research Funding; Karyopharm Therapeutics: Research Funding; Acerta: Research Funding; Incyte: Consultancy; AbbVie: Consultancy; MorphSys: Consultancy; Celgene: Consultancy, Research Funding. Nowakowski:Celgene/BMS: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy; Kymera: Consultancy; Curis: Consultancy; Seattle Genetics: Consultancy; NanoString: Research Funding.

Introduction The molecular basis for the clinical heterogeneity observed in DLBCL was initially elucidated with gene expression profiling, identifying three distinct subgroups with prognostic relevance based on COO namely activated B-cell like (ABC), germinal center B-cell like (GCB) and a type 3 subtype. Shortly afterwards the Han's algorithm was developed allowing for widespread applicability and correlation of gene expression with protein expression. GCB profile at diagnosis is generally associated with superior long term outcomes compared to non-GCB in patients treated with conventional chemo-immunotherapy. Patients with relapsed/refractory disease (R/R) after front-line therapy undergo salvage treatment and, upon demonstration of objective response, proceed with high dose therapy and autologous transplantation (auto-HCT). Whether COO by Han's algorithm retains its prognostic significance post auto-HCT in patients with R/R DLBCL is not well established. Methods A retrospective analysis was carried out using the Mayo database across all three sites. It included all patients between 18-75 years of age who were diagnosed with de-novo DLBCL and underwent first auto-HCT for R/R disease. Patients must have received salvage treatment and shown chemotherapy sensitive disease. Patients with transformed DLBCL or other variants and those who underwent auto-HCT in first complete remission for high risk disease were excluded. Patients who had less than a partial response at time of transplantation and still underwent auto-HCT were also excluded. Primary endpoints included overall survival (OS); relapse and relapse-free survival (RFS). Continuous variables were summarized as mean (standard deviation) and median (range). Categorical variables were reported as frequency (percentage). Continuous baseline variables were compared between GCB and non-GCB using Wilcoxon rank sum test and categorical baseline variables were compared with Chi-squared test. Kaplan-Meier method was used to estimate 5 and 10-year rates of freedom from long-term events and draw corresponding survival curves. Multivariate Cox regression models were used to evaluate the impact of cell of origin on long-term survival after adjusting for baseline factors. All tests were two-sided with alpha level set at 0.05 for statistical significance. Results A total of 357 patients underwent auto-HCT between 2005 and 2018. Cell of origin was determined for 284 patients and these were included in the analysis. Median age was 61 (range: 19-78) years, and 64% patients were male. GCB and non-GCB patients did not differ significantly with regards to baseline factors (Table 1). During a median follow up of 1.7 years, 139 patients died, 151 had relapse and 175 either died or had relapse. Five year OS for GCB patients versus (vs) non-GCB was at 44% vs 64% (p=0.004) (Figure 1); relapse was at 67% vs 49% (p=0.012) and RFS was at 28% vs 50% (p=0.003). The difference between GCB and non-GCB groups remained statistically significant in multivariate analysis, with GCB patients 60% more likely to die and 50% more likely to experience relapse compared to non-GCB patients. The only other factor that retained significance in multivariate analysis for both endpoints was response at the time of transplant (Table 2A-C). Conclusions In this analysis, GCB DLBCL results in worse OS and higher relapse vs. non-GCB DLBCL following an auto-HCT. It is unclear if relapse/progression of GCB subtype after front-line therapy alters its natural history into a more aggressive disease. Disclosures Ansell: Trillium: Research Funding; ADC Therapeutics: Research Funding; Affimed: Research Funding; Bristol Myers Squibb: Research Funding; AI Therapeutics: Research Funding; Takeda: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding. Foran:Xencor: Research Funding; Trillium: Research Funding; Takeda: Research Funding; Kura Oncology: Research Funding; Aptose: Research Funding; Aprea: Research Funding; Actinium: Research Funding; Boehringer Ingelheim: Research Funding; Abbvie: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Revolution Medicine: Consultancy; H3Biosciences: Research Funding; Agios: Honoraria, Research Funding. Tun:Celgene: Research Funding; Mundipharma: Research Funding; Curis: Research Funding; TG Therapeutics: Research Funding; Acrotech: Research Funding; DTRM Biopharma: Research Funding; Bristol-Myers Squibb: Research Funding. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy.

8508 Background: A prior pilot study of epratuzumab (Immunomedics) and rituximab in combination with CHOP chemotherapy (ER-CHOP) in untreated patients with diffuse large B-cell lymphoma demonstrated feasibility and safety. This multicenter NCCTG phase II study was carried out to assess efficacy. Methods: Patients received immunochemotherapy on the following schedule: epratuzumab 360 mg/m2, rituximab 375 mg/m2, and standard dose CHOP every 3 weeks for 6 cycles. Weekly blood counts were obtained to monitor hematological toxicity. Primary endpoint was 12 month event free survival (EFS12). Secondary endpoints were response rate, progression free survival, functional CR (PET negative) and toxicity. Results: 107 patients were accrued from Feb 2006 to Aug 2007. 29 patients were ineligible resulting in 78 eligible patients. Baseline patient characteristics for the eligible patients included median age 61 (range 21–82); 59% were male. 81% had advanced stage; IPI was 0–1 in 17 pts (22%), 2 in 22 pts (28%), 3 in 29 pts (37%) and 4–5 in 10 pts (13%). Based on the revised IPI (R-IPI) 50% were poor/high risk (IPI 3–5). 71% had an elevated LDH. Performance score was 0–1 in 69 pts and 2–3 in 9 pts. The ORR was 95% (CR/CRu: 73%). For the low risk IPI (0–2), ORR was 95% (CR/CRu: 74%) and for the high risk IPI (3–5), ORR was 95% (CR/CRu: 72%). The EFS at 12 months was 80%. The 12 month progression free survival (PFS12) and overall survival (OS12) is 82% and 88% respectively. EFS12, PFS12 and OS12 by IPI risk category is shown ( Table ). Conclusions: ER-CHOP every 21 days is feasible and safe. The ORR, EFS and PFS compare favorably to studies using R-CHOP especially in the high-intermediate and high risk IPI subgroups. A randomized phase III trial of R-CHOP vs ER-CHOP is needed to prove that dual antibody targeting in combination with CHOP is better. [Table: see text] No significant financial relationships to disclose.

AbstractTransplant‐associated thrombotic microangiopathy (TA‐TMA) has a wide range of presentations after hematopoietic stem‐cell transplantation (HSCT). We retrospectively studied the risk factors and outcomes of patients with early (≤day 100) and late (>day 100) TA‐TMA. Among the 1451 HSCT recipients, early TA‐TMA occurred in 45 (3.1%) patients at a median of 27 (3‐91) days, and late TA‐TMA in 39 (2.7%) patients at a median of 303 (122‐2595) days. Patients with early TA‐TMA were more likely to have high blood calcineurin‐inhibitor levels (P < .001) and acute graph‐vs‐host disease (GVHD, P < .001), while late TMA patients were more likely to have chronic GVHD (P < .001). The estimated median overall survival after onset of TMA for the entire cohort was 6 months. The estimated median overall survival was not reached in patients with an improvement of TMA vs 2 months in patients with no improvement (P < .001). In the early TMA group, older age (for every 10 years, HR 1.40; 95% CI 1.00‐1.94; P = .049) and bacterial infection (HR 2.42; 95% CI 0.98‐6.00; P = .056) were positively associated with mortality. Switching to MMF treatment (HR 0.40; 95% CI 0.16‐0.99; P = .047) and improvement of TMA (HR 0.08; 95% CI 0.03‐0.25; P < .001) were negatively associated with mortality in the multivariate analysis. In the late TMA group, the improvement of TMA was the only independent predictor associated with a lower risk of death (HR 0.05; 95% CI 0.02‐0.19; P < .001). Mortality rates in both early and late TMA remain unacceptably high. Future studies are needed for early diagnosis, trigger identifications, and use of targeted treatments.

Abstract Introduction: The immunoglobulin free light chain (FLC) is the precursor protein of amyloid in primary systemic amyloidosis (AL). Historically, the ability to monitor the amyloid protein precursor has been crude. There is now a test that reproducibly measures serum levels of FLC. We evaluated the utility of this assay in patients with AL undergoing peripheral blood stem cell transplant (PBSCT). Methods: Between March 1, 1996 and July 31, 2004, 98 patients with AL undergoing PBSCT had serial FLC measurements performed either prospectively or on stored sera. Patients who died before their 100 day evaluation were excluded because response could not be estimated. FLC levels were performed using Freelite™ reagents on a Dade-Behring Nephelometer. In order to pool the data of the monoclonal kappa and lambda patients, the clonal free light chain was considered the involved] immunoglobulin free light chain for the purpose of these analyses and is henceforth referred to as FLC. The prognostic effects of the initial concentration and the extent of reduction of monoclonal FLC on survival were evaluated. Results: Pre-transplant, 94% of patients had an abnormal FLC ratio, with a median involved FLC of 152 mg/L [15.2 mg/dL]. Only 14% of 98 patients had a “measurable” serum M-spike (i.e. ≥ 10 g/L [1 g/dL]) on electrophoresis with a median of 1 g/L [0.1 g/dL]. Ten patients have died of their disease during a median follow-up time of 19.5 months, range 3.3 to 103 months. The 2- year and 4-year estimated survivals are 92% and 76%, respectively. Using the 75th percentile value of pre-PBSCT FLC (382 mg/L [38.2 g/dL]) as a grouping variable, there was a significantly higher risk of death 5.4 (95% confidence interval 1.5–19.3) in the patient quartile with the highest baseline FLC. Baseline FLC correlated with serum cardiac troponin T levels (rho 0.51, p&lt;0.0001), suggesting that high FLC levels are associated with more advanced disease. After PBSCT, the median percent reduction of FLC was 81%. The percent FLC reduction did not predict for survival, but the absolute level of FLC achieved after therapy did. The hazard ratio for death for not achieving a post-transplant FLC of 20 mg/L [2 mg/dL] post-transplant was 5.1 (95% confidence interval 1.1–24.1). Of 91 patients evaluable for complete response by EBMT criteria, 45 had a complete hematological response. Sixty-five percent of the patients achieving a FLC level of less than 20 mg/L [2 mg/dL] also had a complete hematologic response. Free light chain response as defined by a post transplant FLC level 20mg/L [2 mg/dL] or lower was a more powerful predictor of survival than complete hematologic response, as defined by the EBMT multiple myeloma criteria. Post-PBSCT FLC level only weakly predicted for organ response, but median follow-up for surviving patients is relatively short at 19.6 months. Conclusion: FLC measurements both pre- and post-PBSCT are important predictors of patient outcome.

Abstract Introduction: The association of amyloidosis with immunoglobulin light chain disorders is well recognized. It is less commonly appreciated that amyloidosis can be associated with IgM monoclonal gammopathies. One of the available therapies for treating amyloidosis is stem cell transplantation. It is unknown whether the clinical outcomes in patients with IgM amyloidosis differs from those patients with light chain amyloidosis. Patients: Among 242 amyloidosis patients receiving stem cell transplants 10 (4%) had an IgM monoclonal protein. Eight were Mλ. One was biclonal Mλ Mκ and one was biclonal Mκ Gλ. The age range was 56 to 71, median 64 years. Seven were men. The monoclonal protein ranged in size from 0.1 to 2.3 g/dL (median 1.2 g/dL). Patients were transplanted from 2 to 8 months (median 4 months) following histologic diagnosis of amyloid. The median time from the recognition of the IgM monoclonal protein to the diagnosis of amyloid was 1.3 months, but 2 patients, both of whom had overt Waldenström’s macroglobulinemia, were diagnosed 45 and 115 months respectively before amyloidosis developed. Of the cohort of 10, 3 fulfilled the criteria for symptomatic Waldenström’s macroglobulinemia. Results: Amyloid syndromes were recognized in the kidney, heart, peripheral nerve and liver in 8, 3, 3 and 1 patient, respectively. Of the 3 peripheral neuropathy patients one also had autonomic failure. Seven of the 8 renal amyloid patients were confirmed with a renal biopsy. Their urinary protein loss ranged from 0.1 to 9.5 g/24h with a median of 4.7 g/24h. Six of the 10 patients had single organ involvement, 3 had 2 organ involvement and 1 had 3 organ involvement. All 3 Waldenström’s patients had prior exposure to cytotoxic chemotherapy. Amyloid deposits were seen in the bone marrow, fat and lymph node in 6, 5 and 1 patient, respectively. Patients underwent from 1 to 7 (median 3) apheresis with a median CD34 yield of 4.5 x 106/kg. Conditioning was Melphalan at 140 and 200 mg/m2 in 2 and 8 patients respectively. Neutrophil engraftment 500/μL occurred between day 11 and 30 (median 14) and for platelets 20,000/μL between day 11 and 406 (median day 16). The median number of hospitalization days ranged from 0 to 32 (median 12). Nine of the 10 patients fulfilled criteria for a hematologic response and to date 3 of these 9 have also achieved an organ response, including normalization of urinary protein loss in 2 nephrotic patients and a greater than 50% reduction in urinary protein loss in the third. None of the patients with amyloid neuropathy responded. One of the patients with cardiac amyloid showed echocardiographic evidence of improvement. At this time 8 survive and 2 died; 1 a treatment-related death (day +40) and 1 of relapse post transplant with progressive amyloid at 45 months. The median follow-up of surviving patients is 29 months. Conclusion: The outcomes in patients with IgM amyloidosis following transplantation do not appear to be different from those with immunoglobulin light chain amyloidosis. There is no suggestion that the response rates are lower or that alternate conditioning schemes such as BEAM should be considered.

Abstract Absolute lymphocyte count (ALC) recovery post-autologous stem cell transplantation has been documented as an independent predictor for survival in non-Hodgkin lymphoma. The effect of ALC recovery on survival during standard CHOP or R-CHOP chemotherapy for newly diagnosed diffuse large B cell lymphoma (DLBCL) is unknown. To participate in the study, patients required to receive their full treatment with complete blood count determinations at the Mayo Clinic College of Medicine. Of 1633 DLBCL cases seen at the Mayo Clinic College of Medicine between February 1994 through August 2004, 212 consecutive DLBCL patients were eligible for the study. We study ALC recovery as a prognostic factor for progression-free survival (PFS) and overall survival (OS) in DLBCL patients treated with at least 3 cycles of CHOP or R-CHOP. 57% were male and the median age was 66 years (range: 20 – 87); 42% had elevated LDH, only 11% had a PS of 2 or higher; 58% were low stage (I or II); 88% of pts achieved a complete response. ALC was evaluated at the beginning of each treatment cycle, focusing on cycles 1–3 and the 3 month post treatment sample. ALC for each of the cycles were significantly correlated with PFS and OS, with cycle 1 ALC most significantly correlated when accounting for inherent differences based on treatment (Rx) type (i.e. CHOP vs. R-CHOP) as well as high vs. low IPI (PFS: p = 0.0012; OS: p = 0.005). Also, 74 pts achieved an ALC of at least 1,000 during all three cycles, where there was no significant relationship with this incidence and Rx type; this incidence was significantly associated with higher PFS (p = 0.0007) and OS (p = 0.0006), even when accounting for Rx type and high vs. low IPI. In the 179 pts who had 3-month post-Rx ALC data, this was also significantly associated with PFS (p = 0.002) and OS (p = 0.0009), while still accounting for Rx type and IPI status. Achievement of ALC &gt;= 1,000 post-Rx was also significant for PFS (p = 0.0014) and OS (0.003). Also of note, only cycle 1 ALC was significantly different in high vs. low IPI pts (p = 0.008). In summary, these data support the hypothesis that there is a critical role of lymphocyte (immune) recovery during CHOP/R-CHOP chemotherapy in DLBCL.

Abstract AMD3100, a CXCR4 receptor antagonist, has been studied as a stem cell mobilization agent for the purpose of autologous stem cell transplantation (ASCT) in hematologic malignancies. Lymphocyte subset analysis of peripheral blood in patients treated with AMD3100 has been studied in healthy volunteers. To date, no reports exist describing the lymphocyte subsets of the autograft in patients undergoing AMD3100 stem cell mobilization for the purposes of ASCT in non-Hodgkin lymphoma (NHL). Considering our prior work demonstrating the significant impact of autograft lymphocyte content on clinical outcomes of patients undergoing ASCT for NHL we set out to profile autograft lymphocyte subsets of patients undergoing mobilization with AMD3100. Using flow cytometry, we analyzed aliquots of apheresis products in 7 patients with NHL undergoing AHSCT who received AMD3100 in addition to G-CSF as a part of their mobilization regimen. These results were compared to 29 patients with NHL who had undergone stem cell mobilization with G-CSF alone. There were no significant differences between these two groups of patients in terms of sex, age, performance status, histology, LDH, and number of pretransplant chemotherapeutic regimens. CD34+ cells collected at apheresis did not differ significantly between the groups. However, compared with G-CSF alone, patients that received AMD3100 had an approximate 5-fold increase in CD4+ cells (0.62 x 109 cells/kg vs. 0.12 x 109 cells/kg, p = 0.0004), a 3.5-fold increase in the absolute number of autograft CD3+ cells (1.21 x 109 cells/kg vs. 0.33 x 109 cells/kg, p = 0.0017), and a 2.5-fold increase in CD8+ cells (0.48 x 109 cells/kg vs 0.19 x 109 cells/kg, p = 0.215). A significant increase was also noted in CD4+25+ cell compartment (0.17 x 109 cells/kg vs. 0.006 x 109 cells/kg, p = 0.0001). No significant difference was noted in the absolute number of autograft CD16+56+ NK cells. Finally, an increase in the autograft total absolute lymphocyte count (41.6 x 109 cells/kg vs. 2.88 x 109 cells/kg, p &lt; 0.001) as well as peripheral blood absolute lymphocyte count at day 15 after AHSCT was observed in those patients who had received AMD3100 (0.79 x 109 cells/kg vs. 0.58 x 109 cells/kg, p = 0.04). The increased lymphocyte content of the autograft (total and subset) would suggest the potential of positive impact on clinical outcomes in patients mobilized with AMD3100. Indeed, none of the patients who received AMD3100 had relapsed disease at one year post-transplant (although two of these patients are currently 9 months and 11 months post-transplant respectively), whereas 10 of the 29 control patients had relapsed disease at one year. Further studies are necessary to confirm these observations and ascertain their clinical significance.

Abstract Mantle-cell lymphoma (MCL) is characterized by an aggressive clinical course and poor prognosis with a median survival of only 3 to 4 years. High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is an effective treatment strategy for MCL demonstrating significantly prolongs progression free survival (PFS) when compared to IFNa maintenance therapy of patients in first remission. We have previously shown that absolute lymphocyte count at day 15 (ALC-15) after ASCT is an independent prognostic factor for survival in hematologic malignancies (non-Hodgkin’s lymphoma (NHL), Hodgkin’s disease, multiple myeloma, primary amyloidosis, acute myelogenous leukemia) and breast cancer. The study of ALC-15 after ASCT as a prognosis factor in NHL included different subtypes of lymphomas. The relationship of ALC-15 after ASCT in patients with MCL has not been specifically addressed. Herein we present data evaluating the impact of early lymphocyte recovery (ALC-15) in patients undergoing ASCT for MCL. We retrospectively reviewed the medical records of 42 consecutive patients (9 females and 33 males) with MCL who underwent ASCT at the Mayo Clinic in Rochester from 1993 to 2005. Based on our previous studies, the ALC-15 threshold was set at 500 cells/μL. The median patient age at transplant was 57 years (range, 37–71) and the median follow-up after ASCT was 25 months (range, 2–106 months). The median overall (OS) and PFS times were significantly better for the 24 patients that achieved an ALC-15 ≥ 500 cells/mL compared with 18 patients with ALC-15 &lt; 500 cells/μL (not reached versus 30 months, P &lt; 0.01 and not reached versus 16 months, P &lt; 0.0006, respectively). Multivariate analysis adjusting for other prognostic factors suggests that ALC-15 is an independent prognostic factor for OS and PFS. ALC-15 ≥ 500 cells/mL is associated with significantly improved clinical outcomes following ASCT in patients with MCL.

Abstract Introduction: Stem cell transplant is an increasingly widely applied technique for managing amyloidosis. As in multiple myeloma, the treatment would not be expected to be curative and patients would be expected to relapse in most instances. In addition, approximately one-third of patients fail to respond to initial therapy. The role of second transplantation in treatment failures or patients who relapse is reviewed. Patients: Of 242 patients undergoing high dose conditioning and stem cell transplantation for amyloidosis (AL) at the Mayo Clinic, 6 subsequently underwent a second transplant. Results: Patient 1, who had single organ renal amyloid nephrotic syndrome responded and relapsed at 73 months, received a second stem cell transplant achieving a hematologic complete response with normalization of a markedly elevated pre transplant free light chain (59 to 1.9 mg/dL) and is alive at 12 months. Patient 2 relapsed 42 months after transplant for single organ renal amyloidosis; the second stem cell transplant, has normalized his free light chain ratio reduced his urinary protein loss from 5450 to 1482 mg/day and he is alive 21 months following his second transplant (63 months overall). Patient 3 relapsed 34 months after a response of renal and cardiac amyloidosis. After transplant two, he failed to achieve a 50% reduction in his free light chain, began hemodialysis 7 months post transplant and died one year post transplant. Patient 4 with single organ cardiac involvement relapsed 30 months following his first transplant and died on day +5 of his second transplant of an acute pulmonary embolus. Patient 5 was a response failure after his first transplant, had a second transplant 35 months later, having failed Dexamethasone followed by Melphalan/Dexamethasone therapy, and died 3 months later of progressive disease. Patient 6 had single organ vascular involvement manifest by calf and thigh claudication and failed to respond with his first transplant with a persistently elevated free light chain. The second transplant was performed six months after the first without further free light chain reduction and persistent claudication at 11 months. Conclusion: Patients who failed to achieve a hematologic response after a first transplant appear not to benefit from a second course of high dose therapy. Among 4 patients who were previously responsive and relapsed, one achieved a hematologic complete response, one achieved a hematologic partial response, and two died. The two patients achieving a second hematologic response had the longest response duration (73 and 42 months) following their first transplant, and the second response presumably reflects favorable (indolent; non proliferative) biology of the underlying plasma cell dyscrasia. High dose therapy and stem cell transplant may be an effective salvage regimen for patients who responded to a first transplant and whose response lasted greater than 36 months.