ALBERT

Description: Background: The association of Melphalan, Prednisone and Lenalidomide (MPR) has shown significant anti-myeloma activity in newly diagnosed Multiple Myeloma (MM) patients. In this phase I/II study, the more frequent adverse events were neutropenia and thrombocytopenia. Non-hematologic toxicities were unusual. Methods: We analyzed the kinetics and risk factors for neutropenia and thrombocytopenia in 21 patients (median age 69 years) who received nine four-week cycles of MPR at the maximum tolerated dose (melphalan 0.18 mg/Kg d 1–4, lenalidomide 10 mg d 1–21, prednisone 2 mg/Kg d 1–4, followed by maintenance period with lenalidomide 10 mg/day for 21 days every 4 weeks). We also up-dated efficacy end-point. At the occurrence of grade-3 neutropenia, G-CSF was administered for 5–7 days. The occurrence of grade-4 neutropenia despite G-CSF administration or any other grade-4 hematological toxicities required withholding of treatment and subsequent dose reduction at the start of the following cycle. A new cycle was allowed if the neutrophil count was 〉1×109/L and platelet count 〉50×109/L. A delay of 2 weeks was allowed, a delay beyond 2 weeks required dose reduction and a delay beyond 4 weeks required therapy discontinuation. Results: Grade-3 neutropenia occurred in 38.1% of patients, grade-4 neutropenia in 14.2% of patients, but febrile neutropenia was 9.5%. G-CSF was administered in 42.3% of patients. The mean neutrophil count at the start of each MPR cycle was 2.69 × 109/L (SD 1.4). The mean neutrophil count at nadir (day 15–21) of each cycle was 1.43 × 109/L (SD 1.0). The incidence and depth of neutropenia did not increase with the number of cycles. The mean neutrophil count during maintenance was 2.11 × 109/L (SD 1.0). Grade-3 thrombocytopenia occurred in 14.2% of patients and grade-4 thrombocytopenia in 9.5%; one patient required platelet transfusion. The mean platelet count at the start of each MPR cycle was 174 × 109/L (SD 63.9). The mean platelet count at nadir (day 15–21) of each cycle was 121 × 109/L (SD 56.3). Thrombocytopenia was more pronounced after 9 cycles of treatment. The mean platelet count after 9 cycles was 109 × 109/L (SD 53). The mean platelet count at the end of 6 months of lenalidomide maintenance therapy was 158 × 109/L (SD 79.2). One patient required lenalidomide dose reduction for severe neutropenia. Three patients discontinuated therapy for severe thrombocytopenia and neutropenia. Grade 3–4 hematologic toxicity was more frequent in patients with low baseline neutrophil count and in those with Bence-Jones myeloma. Neutropenic fever (9.5%), cutaneous reaction (9.5%), thromboembolism (4.8%) were the most frequent grade 3–4 non-hematologic adverse events. After a median follow-up of 29.5 months, the median time-to-progression was 28.5 months, the median progression-free survival was 28.5 months and the 2-years overall survival was 90.5%. No death was reported in the first 18 months of treatment. Conclusions: MPR is a promising first line regimen for elderly MM patients. Hematologic adverse events were frequent but manageable with the use of G-CSF.

Description: Introduction: Multiple myeloma (MM) is still an incurable disease and patients may relapse despite achievement of complete remission (CR). Minimal residual disease (MRD) assessment by multiparameter flow cytometry (MFC) on bone marrow (BM) is a sensitive diagnostic tool to measure response and is highly predictive of outcome in MM as previously reported. The aim of this study is to evaluate the role of MRD monitoring by MFC in MM patients receiving novel agents with or without autologous stem cell transplantation (ASCT) and to investigate the efficacy of treatments by using MRD-negativity as a deeper response criteria. Methods: The RV-MM-COOP-0556 (EMN02/HO95 MM) study is a phase III, randomized, trial including newly diagnosed MM patients ≤ 65 years. All subjects received 4 cycles of Bortezomib-Cyclophosphamide-Dexamethasone (VCD) induction, followed by Cyclophosphamide chemotherapy and subsequent stem cell mobilization and collection. Afterward, patients were randomized to receive 4 cycles of Bortezomib-Melphalan-Prednisone (VMP) vs one or two cycles of High-Dose-Melphalan (HDM) followed by ASCT. After intensification patients were secondly randomized to receive two cycles of consolidation with Bortezomib-Lenalidomide-Dexamethasone (VRD) vs no consolidation, followed by Lenalidomide maintenance in both arms. Patients who achieved CR/sCR according to IMWG criteria (Rajkumar et al. Blood 2011) after intensification/consolidation treatment, were eligible for the MRD sub-study. MRD analysis by MFC was performed on BM samples after intensification/consolidation, after 6 courses of maintenance, and thereafter every 6 months until progression, to detect monoclonal plasma cells (PCs). Here, we used a double antibody combination (CD138Fitc/CD20PerCp-Cy5.5/CD117APC/CD45APC-H7/CD38PE-Cy7; cyKappaFitc/cyLambdaPE/CD19PerCp-Cy5.5/CD56APC/CD45APC-H7/CD38 PE-Cy7): one tube was employed to obtain PCs quantification, the other one to validate PCs clonality. MRD-negativity was defined when

Description: Abstract 1940 The combination of Melphalan-Prednisone-Lenalidomide (MPR) has shown promising results in elderly newly diagnosed myeloma patients. In the transplant setting, low-dose chemotherapy (induction) precedes high-dose chemotherapy (autologous transplantation consolidation). This approach reduces tumor mass, with few side effects, before achieving the maximum cyto-reduction with autologous transplantation. The same approach has been designed for the elderly patients. Accordingly induction with lenalidomide plus corticosteroids precedes consolidation with MPR. A two-stage phase II clinical trial was planned to evaluate the safety and efficacy of Lenalidomide-Prednisone (RP) as induction, followed by Melphalan-Prednisone-Lenalidomide (MPR) as consolidation and Lenalidomide as maintenance in elderly myeloma patients. Unfit patients with newly diagnosed symptomatic myeloma older than 65 years were enrolled. No exclusion criteria were included in the protocol, to avoid the selection of fit elderly subjects only. Patients with low blood count, abnormal performance status, hepatic, renal, cardiac or pulmonary functions were enrolled. Patients received 4 RP courses (Lenalidomide 25 mg/day for 21 days every 4 weeks, plus Prednisone 50 mg three times/week for 4 weeks) followed by 6 MPR cycles (Melphalan 2 mg and Prednisone 50 mg three times/week, for 4 weeks plus Lenalidomide 10–15 mg/day for 21 days every 4 weeks) and maintenance with Lenalidomide alone (10 mg/day for 21 days every 4 weeks). Two different dose-levels of Lenalidomide were tested in combination with MP: 15 mg (dose-level 1) and 10 mg (dose-level 2). Each cohort included 12 patients, with additional 22 patients enrolled at dose-level 2. Patients were evaluated for efficacy and toxicity after completion of at least 2 MPR cycles. Forty-six patients (median age 75, range 65–88) were enrolled. Thirty-six patients were evaluable after a median of 7 cycles and a median follow-up of 8.5 months. During RP induction, the most frequent grade 3–4 hematological adverse events were neutropenia (19%), anemia (11 %), thrombocytopenia (6%). During MPR consolidation, grade 3–4 adverse events were neutropenia (45%), and thrombocytopenia (3%). Neutropenia was increased by the addition of melphalan, but both thrombocytopenia and anemia were reduced. Non-hematological toxicities were more frequent during RP cycles and reduced during MPR cycles (cutaneous rash and infections). After RP induction, at least partial response (PR) rate was 67%, at least very good partial response (VGPR) was 17%. After 2 MPR cycles, PR rate increase to 72%, including 22% of patients who achieved at least a VGPR. Conclusions. Induction with RP followed by consolidation with MPR showed a manageable safety profile and reduced the risk of anemia, thrombocytopenia and non-hematological toxicity in unfit elderly myeloma patients. These data will be updated at the meeting. Disclosures: Palumbo: Celgene Srl: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janseen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Lenalidomide in combination with melphalan for multiple myeloma patients at diagnosis. Guglielmelli:Celgene: Honoraria; Janseen-Cilag: Honoraria. Gay:Celgene: Honoraria. Cavallo:Celgene: Honoraria. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janseen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: Background MicroRNAs (miRNAs) are a class of short, non-coding, single stranded RNAs regulating a broad spectrum of processes. Circulating miRNAs are an important emerging biomarker in cancer as well as a possible non-invasive diagnostic solution for a wide range of clinical disorders due to their high stability and association with disease state, although their source still remains uncertain. In multiple myeloma (MM), a plasma cell malignancy, circulating miRNAs have been reported to have a diagnostic and prognostic potential. It is therefore plausible to assume that they are involved in pathogenesis of this disease and thus could be used as diagnostic tool not only for MM, its extramedullary (EM) form but also for monitoring the clinical course of the disease. Therefore, in this study, we aimed to identify such miRNAs. Methods Screening analysis of 667 miRNAs was performed on 5 EM serum samples, 5 newly diagnosed MM samples and 6 healthy donors (HD) serum samples using TaqMan Low Density Arrays (TLDA) from Life Technologies. QPCR was performed for miR-130a on 118 serum samples obtained in Brno from newly diagnosed MM patients (pts) (35 pts), primary and secondary EM (35 pts), relapsed MM (18 pts) and HD (30). Further, 45 serum samples (12 diagnostic and 33 follow-up) of pts reaching VGPR/better response, enrolled in Italian CRD/MEL-200 and EMN-02 studies were used for circulating miRNA estimation. Receiver Operating Characteristic (ROC) analysis was used to calculate specificity and sensitivity of the miRNA as a biomarker. Biochemical characteristics were also available for EM and MM pts from Brno. P values

Description: Background: The role of Minimal residual disease (MRD) as surrogate for survival in Multiple Myeloma (MM) patients is well established. Therefore, new response criteria recommend including Multiparameter Flow cytometry (MFC) and next generation Sequencing (NGS) MRD negativity (minimum sensitivity of 1 in 105 nucleated cell) to deeply characterize complete remission (CR) [Kumar SK, Lancet Oncol 2016]. Here we analyzed and compared MRD data from the FORTE trial both by MFC and NGS techniques. Methods: Newly diagnosed MM patients ≤65 years were randomized to receive carfilzomib, lenalidomide, dexamethasone (KRd) induction - autologous stem cell transplantation (ASCT) intensification - KRd consolidation (KRd_ASCT); KRd12 and carfilzomib, cyclophosphamide, dexamethasone (KCd) induction - ASCT intensification - KCd consolidation (KCd_ASCT). Thereafter, patients were randomized to maintenance therapy with lenalidomide alone or lenalidomide plus carfilzomib. MRD evaluation was performed by 8-color second generation flow cytometry (sensitivity 10-5) in patients who achieved at least a very good partial response (VGPR) before maintenance. In a subgroup of these ≥ VGPR patients, next generation flow (NGF; sensitivity 10-5 - 10-6) was performed. Moreover, in patients achieving ≥ CR, MRD pre-maintenance was also assessed by NGS (Adaptive Biotechnologies, Seattle, WA; sensitivity 10-5 - 10-6). Therefore, only patients achieving ≥ CR have both MFC and NGS evaluations, and we focused on this ≥ CR population to compare MRD results with the 2 techniques. Spearman's rank correlation coefficient was used to measure the concordance between MFC and NGS. Fisher or Pearson's Chi-squared tests were adopted, where appropriate, to evaluate the statistical significance, at the level of 0.05. Results: ≥ CR pre-maintenance was achieved in 233 patients enrolled in the trial; at data cut-off, MFC and NGS data were available for 176/233 (76%) patients who were included in this analysis (62 received KRd_ASCT, 65 KRd12 and 49 KCd_ASCT). Median age of this ≥ CR population is 57 years (IQR 52-62), 14% have International Staging System (ISS) III stage and 26% high risk cytogenetics by FISH features [either del(17p) or t(4;14) or t(14;16)] reflecting baseline clinical features of the entire FORTE population. 139/176 (79%) ≥ CR patients were MFC negative at a cut-off of at least 10-5. Rate of MRD negative MFC among ≥ CR negative in the 3 arms were: 53/62 (85%) in KRd_ASCT, 51/65 (78%) in KRd12 and 35/49 (71%) in KCd_ASCT, reflecting the higher rate of MCF MRD negativity pre-maintenance reported by ITT in the overall population in the 2 KRD arms [Gay F, ASH 2018]. NGS negativity at a cut-off of at least 10-5 was detected in 87/176 (49%) of ≥ CR patients. Rate of MRD negative NGS at least 10-5 among ≥ CR negative in the 3 arms were: 35/62 (56%) in KRd_ASCT, 31/65 (48%) in KRd12 and 21/49 (43%) in KCd_ASCT. NGS negativity at a cut-off 10-6 was detected in 34/123 (28%) of ≥ CR patients (for 53/176 CR patients 10-6 sensitivity was not reached). Rate of MRD negative NGS at least 10-6 among ≥ CR negative in the 3 arms were:14/41 (34%) in KRd_ASCT, 10/44 (23%) in KRd12 and 10/38 (26%) in KCd_ASCT. Thereafter, we have analyzed the concordance between MRD results by the two techniques. Overall (samples at 10-5 and 10-6 sensitivity), Spearman's coefficient is 0.63 (p 〈 0.001); discordances between the two methods have been observed in 54/176 paired samples (30%). In particular, 53 samples (30%) are NGS positive but MFC negative, of which 34/53 (64%) have reached 10-6 sensitivity by NGS. Only 1 MFC positive sample is NGS negative. In a subgroup of patients evaluable both by NGS and NGF (26 paired samples, sensitivity 10-6), Spearman' s coefficient is 0.83 (p 〈 0.001), although a higher sample size is needed to confirm these preliminary concordant results. Conclusion: In patients who achieved ≥ CR, rate of at least 10-5 MRD MCF negativity was 79% and rate of at least 10-5 NGS negativity was 49%. Assessment both by MFC and NGS showed a good concordance, particularly if the same sensitivity is reached. Longer follow up is needed to assess the impact of MFC in comparison with NGS on patients' outcomes, particularly to evaluate if 10-6 NGS or NGF sensitivity may provide further clinical information, possibly identifying patients with very long survival or potentially cured. Disclosures Oliva: Celgene: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Belotti:Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Galli:Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Leadiant (Sigma-Tau): Honoraria; Janssen: Honoraria; Celgene: Honoraria. Offidani:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Vozella:Amgen: Honoraria; Celgene: Honoraria. Zambello:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Kirsch:Adaptive Biotechnologies: Employment. Jacob:Adaptive Biotechnologies: Employment, Other: shareholder. Ballanti:Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Corradini:Roche: Honoraria; Sanofi: Honoraria; KiowaKirin: Honoraria; Kite: Honoraria; Novartis: Honoraria, Other: Travel Costs; BMS: Other: Travel Costs; Servier: Honoraria; Takeda: Honoraria, Other: Travel Costs; Gilead: Honoraria, Other: Travel Costs; AbbVie: Consultancy, Honoraria, Other: Travel Costs; Amgen: Honoraria; Celgene: Honoraria, Other: Travel Costs; Daiichi Sankyo: Honoraria; Jazz Pharmaceutics: Honoraria; Janssen: Honoraria, Other: Travel Costs. Omedé:Janssen: Membership on an entity's Board of Directors or advisory committees. Cavo:takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Musto:Amgen: Honoraria; Celgene: Honoraria. Boccadoro:Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding. Gay:AbbVie: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: The presentation includes discussion of off-label use of a drug or drugs for the treatment of multiple myeloma.

Description: Abstract 3419 Poster Board III-307 Background Bortezomib induction before autologous stem cell transplantation (ASCT) has shown its efficacy in newly diagnosed multiple myeloma (MM) patients, both in association with dexamethasone alone (Harousseau JL, et al. Blood 110, 2007, abstr 450) and in combination with doxorubicin and dexamethasone (Popat R, et al. Br J Haematol 141:512-516, 2008). Lenalidomide, a less toxic and more potent thalidomide-derivative, lacks the neurotoxic effects of the parent drug and represents an optimal agent to include in maintenance regimens. Aims These observations provided the rationale for investigating a sequential approach including bortezomib as induction and lenalidomide as consolidation-maintenance in MM patients undergoing ASCT. Methods A hundred and two newly diagnosed patients aged 65–75 years were enrolled in 17 Italian centers. Induction (PAD) included four 21-day cycles of bortezomib (1.3 mg/m2 days 1,4,8,11), pegylated-liposomal-doxorubicin (30 mg/m2 day 4), and dexamethasone (40 mg/day: cycle 1, days 1–4, 8–11, 15–18; cycles 2–4, days 1–4). Autologous transplantation was tandem melphalan 100 mg/m2 (MEL100) followed by stem-cell support. After ASCT, patients received consolidation with four 28-day cycles of lenalidomide (25 mg/day days 1–21 every 28 days) plus prednisone (50 mg every other day) (LP), followed by maintenance (L) with lenalidomide alone (10 mg/day days 1–21 every 28 days) until relapse. Primary endpoints were safety (incidence of grade 3–4 adverse events [AEs]) and efficacy (response rate). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Time-to-event estimates analysis was performed using the Kaplan-Meier method. Results Very good partial response (VGPR) or better was 58% after PAD induction and increased to 82% after MEL100 and to 86% during LP-L. Complete response (CR) rate was 13% after PAD induction, increased to 38% after MEL100 and to 66% during LP-L. After a median follow-up of 2 years, the 2-year PFS was 69%, the 2-year time-to-progression was 75% and the 2-year OS was 86%. During PAD induction, main grade 3–4 AEs were thrombocytopenia (17%), neutropenia (10%), peripheral neuropathy (16%), and pneumonia (10%); treatment-related mortality was 3%. During consolidation-maintenance grade 3–4 AEs included neutropenia (16%), thrombocytopenia (6%), pneumonia (5%), and cutaneous rash (4%). Consolidation-maintenance treatment was well tolerated: only 4% of patients required Granulocyte-colony stimulating factor support and no patient required platelet transfusion; dermatological toxicity was easily manageable with dose-reduction and supportive therapy; no treatment-related deaths were reported. Updated results will be presented at the meeting. Conclusion This is the first phase II study in newly diagnosed MM patients to date, where a sequential approach including bortezomib as induction, and lenalidomide as post ASCT consolidation-maintenance was explored. Treatment was correlated with an increase in response rate and in the depth of response (CR rate) and was generally well tolerated. These data suggest that this is a safe and effective regimen for newly diagnosed MM patients. Randomized trials are needed to confirm these results. Disclosures Patriarca: Celgene: Honoraria; Janssen Cilag: Honoraria. Bringhen:Celgene: Honoraria; Janssen Cilag: Honoraria. Boccadoro:Janssen Cilag : Consultant, advisory committee, Research Funding; Celgene: Consultant, advisory committee, Research Funding; Pharmion: Consultant, advisory committee, Research Funding. Palumbo:Celgene: Honoraria; Janssen Cilag: Honoraria.

Description: Background: In multiple myeloma (MM), different clinical parameters and molecular prognostic factors can predict disease course and response to therapy. The classification of myeloma patients includes laboratory parameters associated with higher tumor activity, resistance to therapy and proliferative competence. Tumor circulating plasma cells (TCPC) in MM patients showed a strong correlation with a more aggressive disease. Aim: For the first time, we quantified the amounts of TCPC with single platform flow cytometric method and evaluated their relationship with patients' baseline characteristics and response to therapy before maintenance. Methods: Whole peripheral blood samples from 413 newly diagnosed MM patients ≤65 years enrolled in the UNITO-MM-01/FORTE trial were collected. Patients were randomized [1:1:1; stratification: International Staging System (ISS) and age] to ARM A: carfilzomib-cyclophosphamide-dexamethasone (KCyd) followed by melphalan 200 mg/m2 and autologous stem-cell transplantation (MEL200-ASCT) and consolidation with 4 KCyd; ARM B: carfilzomib-lenalidomide-dexamethasone (KRd) followed by MEL200-ASCT and 4 KRd; ARM C: 12 KRd cycles. Enrollment was completed in March 2017; data cut-off was November 30, 2018. For the single platform tube, the antibody combination CD38PC7/CD138PC5.5/ CD45KO/CD56PE/CD19PB was mixed with 100µL of EDTA peripheral blood, dispensed with reverse pipetting, and incubated for 15 min, added with 500µL of lysing solution and, after 15 min, 100µL of flow count fluorospheres were dispensed with reverse pipetting and cells acquired with Navios flow cytometer. Intracytoplasmic tube was set up to confirm the clonality of CPC. Results: Circulating plasma cells (CPC) were quantified in 413 samples, with median values of 0.03% (range: 0-51%) and 2.37/mm3 (range: 0-6272/mm3). White blood cells were 5710/mm3 (range: 1752-26102/mm3); total events acquired 1285000 (range: 40000-2000000); median CPC events were 58 (range: 0-441000); cellular events acquired were 190000 (range: 4428-1300000). In 390 out of 413 samples (94.4%), CPC were detected; 272 samples (66%) showed TCPC with a median of 1.24/mm3 (range 0.06- 6272/mm3). Patients were sorted according to different baseline characteristics and the medians of absolute TCPC were compared. The most statistically significant differences (p