A systematic review of contemporary phase I trials in patients with lymphoma.

We performed a systematic review of phase I trials specifically designed for lymphoma patients. PubMed and Cochrane Library databases were searched using (lymphoma*) AND (phase 1) and publication date 2015-2020 to identify phase I dose-finding trials including a majority of lymphoma patients. Eighty-two trials (n = 3289 lymphoma patients) were included: 46 (55%) enrolled only lymphoma patients, 34 (41%) included also other hematologic malignancies, 2 (2%) solid tumors. Forty-six trials (56%) evaluated a combination (in 25 addition of experimental drug to standard therapy). Seven trials (9%) enrolled untreated patients. Among trials reporting activity in lymphoma patients, 74% (n = 57) reported an overall response rate ≥ 30%. All trials reported grade ≥ 3 adverse events; however, rates were not comparable across trials. Thirty-one treatment-related deaths in lymphoma patients were reported (overall treatment-related grade 5 adverse events rate 0.94%). Phase I trials designed for lymphoma patients were generally safe and the majority reported overall response rate ≥ 30%.

Predictors of the trajectory of cognitive functioning in the first 6 months after allogeneic hematopoietic stem cell transplantation.

Certain subgroups of patients may be particularly vulnerable to cognitive decline after treatment with allogeneic hematopoietic stem cell transplant (HCT). The objective of this study was to identify predictors of cognitive functioning changes within the first 6 months after HCT. Fifty-eight adults treated with allogeneic HCT (53% male, mean 48 years of age) completed neuropsychological tests of learning/memory, psychomotor efficiency/processing speed, and executive functioning/working memory at three time points: pre-HCT and day 100 and 6 months post transplant. On average, there was significant improvement in learning/memory (p = 0.002), psychomotor efficiency/processing speed (p < 0.0001), and executive functioning/working memory (p < 0.0001), at 6 months. Multilevel modeling identified predictors of divergence from this trajectory; Karnofsky performance status <80 was associated with worsening learning/memory over time; peak severity of acute graft-versus-host disease >=Grade 2 was associated with worsening psychomotor efficiency/processing speed; and greater years of education predicted a faster improvement in psychomotor efficiency/processing speed. Other factors were associated with cognitive functioning over time: higher intelligence quotient (IQ) was associated with better cognitive functioning, and older age, being male, and greater pretransplant comorbidities were associated with worse cognitive functioning. Overall, cognitive performance appears to improve over the first 6 months after transplant. However, pretransplant and posttransplant factors may influence this trajectory.

Aspergillus galactomannan detection in exhaled breath condensate compared to bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in immunocompromised patients.

OBJECTIVES: Exhaled breath condensate (EBC) is a noninvasive means of sampling the airways that has shown significant promise in the diagnosis of many disorders. There have been no reports of its usefulness in the detection of galactomannan (GM), a component of the cell wall of Aspergillus. The suitability of EBC for the detection of GM for the diagnosis of invasive aspergillosis (IA) using the Platelia Aspergillus enzyme-linked immunosorbent assay was investigated. METHODS: Prospective, cross-sectional study of lung transplant recipient and haemotologic malignancy patients at a university centre. EBC samples were compared to concomitant bronchoalveolar lavage (BAL) samples among lung transplant recipients and healthy controls. EBC was collected over 10 minutes using a refrigerated condenser according to the European Respiratory Society/American Thoracic Society recommendations, with the BAL performed immediately thereafter. RESULTS: A total of 476 EBC specimens with 444 matched BAL specimens collected from lung transplant recipients (n = 197) or haemotologic malignancy patients (n = 133) were examined. Both diluted and untreated EBC optical density (OD) values (0.0830, interquartile range (IQR) 0.0680-0.1040; and 0.1130, IQR 0.0940-0.1383), respectively, from all patients regardless of clinical syndrome were significantly higher than OD values in healthy control EBCs (0.0508, IQR 0.0597-0.0652; p < 0.0001). However, the OD index values did not correlate with the diagnosis of IA (44 samples were associated with IA). Furthermore, no significant correlation was found between EBC GM and the matched BAL specimen. CONCLUSIONS: GM is detectable in EBC; however, no correlation between OD index values and IA was noted in lung transplant recipients.

Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial.

Background: Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) ≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus. Patients and methods: Patients with high-risk (IPI ≥3) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were randomized to 1 year of everolimus 10 mg/day or placebo. The primary end point was DFS; secondary end points were overall survival, lymphoma-specific survival, and safety. Results: Between August 2009 and December 2013, 742 patients were randomized to everolimus (n = 372) or placebo (n = 370). Median follow-up was 50.4 months (range 24.0-76.9). Overall, 47% of patients were ≥65 years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% versus 12%) and relapsed disease (6% versus 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI 0.69-1.22; P = 0.276). Two-year DFS rate was 77.8% (95% CI 72.7-82.1) with everolimus and 77.0% (95% CI 72.1-81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes. Conclusions: Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained. ClinicalTrials.gov: NCT00790036.

International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017).

In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.

Surface proteomics on nanoparticles: a step to simplify the rapid prototyping of nanoparticles.

Engineered nanoparticles for biomedical applications require increasing effectiveness in targeting specific cells while preserving non-target cells' safety. We developed a surface proteomics method for a rapid and systematic analysis of the interphase between the nanoparticle protein corona and the targeted cells that could implement the rapid prototyping of nanomedicines. Native nanoparticles entering in a protein-rich liquid medium quickly form a macromolecular structure called protein corona. This protein structure defines the physical interaction between nanoparticles and target cells. The surface proteins compose the first line of interaction between this macromolecular structure and the cell surface of a target cell. We demonstrated that SUSTU (SUrface proteomics, Safety, Targeting, Uptake) provides a qualitative and quantitative analysis from the protein corona surface. With SUSTU, the spatial dynamics of the protein corona surface can be studied. Data from SUSTU would ascertain the nanoparticle functionalized groups exposed at a destiny that could circumvent preliminary in vitro experiments. Therefore, this method could implement in the analysis of nanoparticle targeting and uptake capability and could be integrated into a rapid prototyping strategy which is a major challenge in nanomaterials science. Data are available via ProteomeXchange with the identifier PXD004636.

Plerixafor for autologous stem-cell mobilization and transplantation for patients in Ontario.

BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation (asct) is an accepted part of standard therapy for patients with hematologic malignancies. Usually, stem-cell mobilization uses granulocyte colony-stimulating factor (g-csf); however, some patients are not able to be mobilized with chemotherapy and g-csf, and such patients could be at higher risk of failing mobilization. Plerixafor is a novel mobilization agent that is absorbed quickly after subcutaneous injection and, at the recommended dose of 0.24 mg/kg, provides a sustained increase in circulating CD34+ cells for 10-18 hours. The main purpose of the present report was to evaluate the most current evidence on the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct for patients in Ontario so as to make recommendations for clinical practice and to assist Cancer Care Ontario in decision-making with respect to this intervention. METHODS: The medline and embase databases were systematically searched for evidence from January 1996 to March 2015, and the best available evidence was used to draft recommendations relevant to the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct. Final approval of this practice guideline report was obtained from both the Stem Cell Transplant Steering Committee and the Report Approval Panel of the Program in Evidence-Based Care. RECOMMENDATIONS: These recommendations apply to adult patients considered for asct: ■ Adding plerixafor to g-csf is an option for initial mobilization in patients with non-Hodgkin lymphoma or multiple myeloma who are eligible for asct when chemotherapy cannot be used and only g-csf mobilization is available.■ For patients with a low peripheral blood CD34+ cell count (for example, <10/µL) at the time of anticipated stem-cell harvesting, or with an inadequate first-day apheresis collection, it is recommended that plerixafor be added to the mobilization regimen to maximize stem-cell collection and to prevent the need for remobilization.■ It is recommended that patients who have failed a previous mobilization attempt undergo remobilization with g-csf and plerixafor, with or without chemotherapy.

Relationship between neurocognitive functioning and medication management ability over the first 6 months following allogeneic stem cell transplantation.

Although neurocognitive impairment has been established as a major issue among cancer survivors, the real-world consequences of this impairment are unclear. This study investigated the relationship between neurocognitive functioning and medication management ability over time among 58 patients treated with allogeneic hematopoietic stem cell transplantation (HCT). Participants completed a neuropsychological test battery and a simulated medication management task at three time points: pre-transplant (T0), Day 100 (T1) and 6 months post transplant (T2). Neurocognitively impaired participants performed worse on the medication management task than neurocognitively normal participants at each time point, and were more likely to score in the impaired range of medication management ability post transplant (72% vs 20%, P<0.001 at T1; 67% vs 23%, P=0.013 at T2). In multivariate analyses, worse performance in executive functioning/working memory consistently predicted impaired medication management ability, even when controlling for sociodemographic and clinical confounders (odds ratio=0.89, 95% confidence interval (0.80, 0.98), P=0.023). Lower physical symptom distress also predicted impaired medication management ability, but this effect decreased over time. Self-reported cognitive problems were not correlated with medication management ability at any time point. Findings suggest that poor neurocognitive functioning, particularly in the domain of executive functioning/working memory, is associated with worse medication management ability within the first 6 months after allogeneic HCT.

Patient age, remission status and HCT-CI in a combined score are prognostic for patients with AML undergoing allogeneic hematopoietic cell transplantation in CR1 and CR2.

For AML, older age, advanced disease and increased hematopoietic cell transplant comorbidity index (HCT-CI) are associated with worse prognosis following allogeneic hematopoietic cell transplantation (HCT). This single-center retrospective study investigated the influence of pre-transplant characteristics on outcomes of 387 patients undergoing allogeneic HCT for AML in CR1 and CR2. The multivariable analysis model for overall survival (OS) included age (hazard ratio (HR)=2.24 for ages 31-64 years and HR=3.23 for age ⩾65 years compared with age ⩽30 years, P=0.003), remission status (HR=1.49 for CR2 compared with CR1, P=0.005) and HCT-CI score (HR=1.47 for ⩾3 compared with <3, P=0.005). Transplant year was significantly associated with OS (P=0.001) but this did not influence the model. A weighted score was developed with age ⩽30, CR1 and HCT-CI score <3 receiving 0 points each, and CR2 and HCT-CI score ⩾3 receiving 1 point each. Ages 31-64 received 2 points, age ⩾65 received 3 points. Scores were grouped as follows: scores 0-1 (low risk, n=36), score 2 (intermediate-low risk, n=147), score 3 (intermediate-high risk, n=141) and scores 4-5 (high risk, n=63) with 3-year OS of 71%, 55%, 42% and 29% for scores 0-1, 2, 3 and 4-5, respectively (P<0.0001). The score predicted nonrelapse mortality (P=0.03) but not cumulative incidence of relapse (P=0.18). This model should be validated for the pre-HCT assessment of AML patients in CR1 and CR2.

Outcomes of patients with therapy-related AML/myelodysplastic syndrome (t-AML/MDS) following hematopoietic cell transplantation.

We studied outcomes of 65 consecutive patients with therapy-related AML/myelodyplastic syndrome (t-AML/MDS) who underwent allogeneic hematopoietic cell transplantation (HCT). Previously published scores of HCT-CI, CIBMTR, EBMT and Comorbidity-age index were also evaluated. Median follow-up of survivors was 72 months (range 16-204). At 2 years, overall survival (OS) was 34% (95% confidence interval (CI) 23-45). Nineteen patients (29%) had monosomal karyotype (MK). Patients with MK had an OS of 21% (95% CI 7-41) at 2 years. Abnormal adverse cytogenetics, unrelated donor, bone marrow graft and CIBMTR score were significant risk factors for OS on univariate analysis. On multivariate analysis, abnormal adverse cytogenetics (hazard ratio (HR) 2.7; 95% CI 1.02-7.2; P-value=0.02) and unrelated donor (HR 2.7; 95% CI 1.5-5.0; P-value=0.0013) were independent factors for survival. Non-relapse mortality (NRM) at 2 years was 31% (95% CI 15-47). Donor type was the only factor that was significant for NRM with matched related donors having an NRM of 20% (95% CI 0-42) whereas unrelated donors had NRM of 60% (95% CI 40-80; P-value=0.0007). In conclusion, patients with t-AML/MDS have poor OS. Unrelated donor is a significant risk factor for both higher NRM and decreased OS. Cytogenetics are predictive for OS.

Comparable outcomes post allogeneic hematopoietic cell transplant for patients with de novo or secondary acute myeloid leukemia in first remission.

Secondary AML (sAML) has a poor prognosis with conventional chemotherapy alone. Allogeneic hematopoietic cell transplantation (HCT) is beneficial for high-risk AML. Data comparing outcomes of transplants for patients with de novo and sAML are limited. We compared outcomes of patients transplanted for de novo and sAML in first complete remission and investigated the effect of age, HCT comorbidity index (HCT-CI) and karyotype in both groups. A total of 264 patients with de novo (n=180) and sAML (n=84) underwent allogeneic HCT between 1999 and 2013. Median age at transplant was 51 years (range 18-71), median follow-up of survivors was 77 months. Evaluation of all patients demonstrated no significant difference between de novo and sAML for overall survival (P=0.18), leukemia-free survival (P=0.17), cumulative incidence of relapse (P=0.51) and non-relapse mortality (P=0.42). Multivariable and propensity score analyses confirmed the comparable outcomes between de novo and sAML post transplant. Although sAML demonstrates outcomes inferior to de novo AML treated with chemotherapy alone, outcomes following allogeneic HCT are comparable between the two groups.

Risk model incorporating donor IL6 and IFNG genotype and gastrointestinal GVHD can discriminate patients at high risk of steroid refractory acute GVHD.

Steroid refractory acute GVHD (SR aGVHD) is associated with high morbidity and mortality. This study attempted to generate a risk model for SR aGVHD using 259 single nucleotide polymorphisms (SNPs) in 53 genes of recipients and donors. A total of 268 patients with aGVHD who were treated with systemic steroids were included. Patients were randomly divided into training (n=180) and validation sets (n=88). Clinical risk factors were also evaluated. In the training set, 85 (47.2%) developed SR aGVHD. Gastrointestinal involvement (P<0.0001) and donor genotypes of IL6 (rs1800797; P=6.2 × 10(-4)) and IFNG (rs2069727; P=4.4 × 10(-4)) were significant risk factors. Scores were assigned to the above risk factors. Patients were divided into low (score 0, n=74) vs high risk (scores 1-3; n=106) in risk model. Higher incidence of SR aGVHD was noted in the high risk (61.3%) vs the low-risk group (27%; P<0.0001, odds ratio (OR) 4.28). Predictive effect of risk model was replicated in the validation set (P=0.0045, OR 3.74). This risk model was associated with response to therapy, overall and GVHD-specific survival and non-relapse mortality. Our study suggested that this risk model could identify patients at high risk of SR aGVHD with donor genotype of IL6 (rs1800797) and IFNG (rs2069727) along with gastrointestinal involvement of aGVHD.

The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD.

Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic SCT (allo-HSCT). Several risk factors have been suggested including BU-containing myeloablative conditioning, unrelated donors and GVHD, but these have not been consistently reported. We conducted a retrospective study including 339 allo-HSCT recipients between 2009 and 2012. Of 339 patients, 79 (23.3%) developed HC with 2-year cumulative incidence of 24.0% (95% confidence interval, 19.4-28.9). The median onset time was 45 days (range, 16-430) after allo-HSCT. Sixty-two patients (84%) out of 74 evaluated for urine BK virus PCR testing showed a positive result (mean 2.0 × 10(10) copies of DNA per mL). In univariate analysis, myeloablative conditioning, HLA-mismatched donor, CMV viremia and acute GVHD (aGVHD) grade 3-4 were significantly associated with the risk of HC. Multivariate analysis confirmed all associating factors identified in univariate analysis except for HLA-mismatched donor: myeloablative conditioning (hazard ratio (HR) 2.63, P=0.003), CMV viremia (HR 1.88, P=0.014) and aGVHD grade 3-4 (HR 1.71, P=0.029). HC did not affect OS or non-relapse mortality. Symptomatic HC is a frequent complication following allo-HSCT, with a 2-year cumulative incidence of 24.0%. Three clinical factors associated with HC were identified including myeloablative conditioning, CMV viremia and severe aGVHD.

Allogeneic hematopoietic cell transplantation for myelofibrosis using fludarabine-, intravenous busulfan- and low-dose TBI-based conditioning.

Graft failure is one of the major barriers to the success of allogeneic hematopoietic cell transplantation (HCT) in myelofibrosis (MF). We report our institutional experience with 27 MF patients who underwent HCT using fludarabine-, intravenous BU- and low-dose total body irradiation (FBT)-based reduced-intensity (n=20) or full-intensity (n=7) conditioning regimens. Eight patients had prior exposure to JAK1/2 inhibitor therapy; six patients received JAK1/2 inhibitors leading on to HCT and two patients received transplant at the failure of JAK1/2 inhibitor therapy. No adverse impact of JAK1/2 inhibitor therapy was observed on early post-transplant outcomes. All evaluable patients had neutrophil recovery, and no primary graft failure was observed. Cumulative incidence of grades II-IV acute GVHD at day 100 was 48% (95% confidence interval (CI), 29-67%) and chronic GVHD at 2 years was 66% (95% CI, 49-84%). Cumulative incidences of nonrelapse mortality (NRM), relapse and probability of OS at 2 years were: 43% (95% CI, 12-74%), 10% (95% CI, 0-39%) and 56% (95% CI, 28-77%), respectively. FBT-based conditioning regimen has a favorable impact on engraftment; however, further efforts are required to reduce NRM.

Extracorporeal photopheresis in the management of graft-versus-host disease.

QUESTION: Is there a benefit associated with the use of extracorporeal photopheresis (ecp) compared with other treatment options for patients who have received allogeneic stem-cell transplantation (sct) and are experiencing graft-versus-host disease (gvhd), if response rate, survival, or improvement in symptoms are the outcomes of interest? PERSPECTIVES: After allogeneic sct, gvhd is a common complication historically categorized as either acute (agvhd: onset ≤100 days post-transplantation) or chronic (cgvhd: >100 days post-transplantation). Graft-versus-host disease occurs when the donor's immune cells recognize the host patient's tissues and organs as foreign and attack them, causing a multitude of problems, often in liver, gastrointestinal system, and skin. Photopheresis is one therapy that has emerged since the early 2000s for the management of steroid-refractory gvhd because of its steroid-sparing ability, low associated toxicity, and efficacy in some clinical settings. The present recommendation report summarizes the available data about photopheresis for the treatment of gvhd and provides recommendations on its use. METHODOLOGY: The medline (Ovid) database was systematically searched for January 1995 to August 2013, and the best available evidence was used to draft recommendations relevant to adult and pediatric patients in Ontario who have received allogeneic sct and are experiencing gvhd. Draft recommendations were first reviewed by clinical and methodology experts before undergoing internal review. Final approval of this practice guideline report was obtained from both the Stem Cell Transplant Steering Committee and the Report Approval Panel of the Program in Evidence-Based Care. RECOMMENDATIONS: These recommendations apply to adult and pediatric patients who have received an allogeneic sct and are experiencing gvhd: ecp is an acceptable therapy for the treatment of steroid-dependent or refractory agvhd in adult and pediatric patients.ecp is an effective therapy for the treatment of steroid-dependent or refractory cgvhd in adult and pediatric patients. QUALIFYING STATEMENT: In Ontario, ecp is currently a covered therapy for patients with steroid-refractory gvhd who meet certain eligibility criteria.

Risk stratification of organ-specific GVHD can be improved by single-nucleotide polymorphism-based risk models.

We aimed to develop a risk model, based on single-nucleotide polymorphism (SNP) markers associated with an increased risk of organ-specific GVHD in 394 transplant pairs. A total of 259 SNPs were genotyped in 53 genes and evaluated for their associated risk of organ-specific GVHD. Risk models were generated using both clinical factors and genetic SNP markers. Patients were stratified by quartiles according to their risk scores and then categorized into three groups (low, intermediate and high risk) according to this model. We compared the risk of overall and organ-specific GVHD amongst these groups. Several SNP markers in the cytokine-, apoptosis-, TGF-ß- and PDGF-mediated pathways were identified as correlative markers of acute and chronic GVHD. Each organ-specific GVHD shared some common biologic pathway such as cytokine, TGF-ß- or PDGF-mediated pathways. However, we also identified different SNP markers that correlated with increased risk of organ-specific GVHD (for example, FCGR2A SNP for oral GVHD, and FAS and TGFB1 SNP for lung GVHD). The incorporation of genetic risk factors into the clinical factors risk model improved stratification power for organ-specific GVHD. The SNP-based approach was suggested to improve risk stratification of organ-specific GVHD.

Duration of first remission, hematopoietic cell transplantation-specific comorbidity index and patient age predict survival of patients with AML transplanted in second CR.

Allo-SCT is potentially curative for patients with AML. Patients transplanted in CR2 tend to experience inferior survival compared with those in CR1. We retrospectively investigated the impact of pretransplant variables on the outcome of patients transplanted with AML in CR2. Ninety-four patients with AML in CR2 received a transplant between 1999 and 2011 with myeloablative (MA, n=65) or reduced-intensity conditioning regimens (RIC, n=29). Variables investigated included cytogenetic risk at diagnosis (SWOG), hematopoietic cell transplantation-specific comorbidity index (HCT-CI), CMV status, duration of CR1 and age. Median age of all patients was 47 years (range 18-70). Multivariable analysis for OS identified three prognostically significant categories: a favorable risk group included patients with duration of CR1 ≥6 months, age <55 years and HCT-CI score 0-3, an intermediate risk group with duration of CR1 ≥6 months, age <55 years and HCT-CI score 4-5 and a high-risk group with duration of CR1 <6 months or age ≥55 years (P=0.0001) with 5-year survivals of 53%, 31% and 6%, respectively. Acute and chronic GVHD did not influence this risk stratification. The stated risk factors discriminate patients with different OS and may assist in decision making for allo-SCT.

Outcome of patients with transformed indolent non-Hodgkin lymphoma referred for autologous stem-cell transplantation.

BACKGROUND: The proportion of potentially eligible patients with transformed indolent non-Hodgkin lymphoma who undergo autologous stem-cell transplantation (ASCT) is unknown. There are limited data describing their outcome in the rituximab era. PATIENTS AND METHODS: We reviewed 105 consecutive patients with biopsy-proven transformation referred to Princess Margaret Hospital for consideration of ASCT during 1996-2009. Patients received anthracycline or platinum-based chemotherapy with or without rituximab. Responders proceeded to stem-cell mobilization and ASCT. RESULTS: The median age at transformation was 54 (range 30-65) years. Patients received a median of two chemotherapy regimens for transformation, including rituximab in 39%. Fifty patients (48%) proceeded with ASCT and 55 (52%) did not, mainly due to progressive disease (n = 42). Three-year overall (OS) and progression-free survival (PFS) post-ASCT were 54% and 42%, respectively. Patients receiving rituximab with chemotherapy before transplant had a 3-year post-ASCT OS of 71% versus 47% in those who received chemotherapy alone (P = 0.046). Patients transplanted after 2004 had a 3-year post-ASCT OS of 69% versus 39% in those receiving ASCT earlier (P = 0.009). CONCLUSIONS: About half of transplant-eligible patients with transformation are able to undergo ASCT. Outcomes following ASCT appear to have improved over recent years, although the role of rituximab in this patient population requires further evaluation.

Large granular lymphocytosis and its impact on long-term clinical outcomes following allo-SCT.

A total of 418 patients receiving hematopoietic SCT and surviving beyond day 100 were examined for the occurrence of large granular lymphocytes (LGLs). LGL lymphocytosis was defined as the presence of at least two of the following criteria: (1) sustained lymphocytosis above 3.0 × 10(9)/L observed in at least three consecutive determinations over a time frame of 2-3 months, (2) predominance (>30%) of LGLs in peripheral blood, (3) confirmation of monoclonality by T-cell receptor analysis using PCR 77 patients developed LGL lymphocytosis during their post-transplant course with a median onset of 312 days from transplant. The cumulative incidence at 1-, 2- and 3-years was 12.3±1.8, 20.8±2.4 and 23.6±2.7%. Patients with LGL lymphocytosis showed an OS advantage (86.2 vs 53.8%, P<0.001), lower non-relapse mortality (NRM; 3.2 vs 27.3%, P<0.001) and lower relapse incidence (9.6 vs 29.4%, P<0.001). Three clinical factors were associated with the development of LGL lymphocytosis: (1) CMV seropositive recipients (CMV-R(+)) compared with CMV seronegative recipients (CMV-R(-); P<0.001) regardless of CMV serostatus of donor; (2) CMV reactivation (P<0.001); (3) chronic GVHD (P=0.007). In conclusion, the incidence of LGL lymphocytosis following allogeneic hematopoietic SCT was detected in ~20% of recipients and is associated with favorable outcomes.

High-dose chemotherapy and auto-SCT in elderly patients with Hodgkin's lymphoma.

Our purpose was to assess efficacy and toxicity of high-dose chemotherapy (HDCT) and ASCT in patients with relapsed and refractory Hodgkin's lymphoma (HL) aged 60 years and older and compare the results with a group of younger HL patients treated in a similar manner. We identified 15 consecutive patients, with HL aged 60 years and older who underwent HDCT (etoposide 60 mg/kg+ melphalan 160 mg/m(2)) and ASCT at our institution from May 2001 to March 2008. The results were compared with a cohort of 157 younger HL patients treated in a similar manner from January 1999 to December 2006. After a median follow-up of 2.5 years, PFS at 3 years after ASCT was 73% (95% confidence interval (CI) 37-90) for the older group and 56% (95% CI 46-64) for the younger group (P=0.45); OS after ASCT was 88% (95% CI 39-98) for the older group and 84% (95% CI 75-90) for the younger group (P=0.80). No transplant-related deaths were seen. Our study suggests that ASCT is feasible for selected elderly patients with HL, giving similar results to younger patients in terms of survival and toxicity.