Search

Considerable healthcare resource utilization and financial burden have been associated with the treatment of WM; however, the impact of health insurance status on outcomes has not been previously reported. We conducted a National Cancer Database analysis of newly diagnosed cases of active WM between 2004 and 2017 to evaluate the impact of insurance status on outcomes. For patients <65 years old ( n  = 1249, male sex: 62.4%, median age: 58 years), significant insurance-based survival differences were observed on multivariable analysis; patients who were uninsured [ n  = 63; HR 3.11 (95%CI, 1.77-5.45), p  < 0.001], on Medicaid [ n  = 87; HR 1.88 (95% CI, 1.01-3.48), p  = 0.045], or on Medicare [ n  = 122; HR 2.78 (95%CI, 1.76-4.38), p  < 0.001], had inferior survival compared to patients with private insurance ( n  = 977; reference). In patients ≥65 years, no insurance-based survival differences were found ( p  = 0.10). Overall, significant insurance-based outcome disparities exist in WM. Further work is desperately needed to systematically uncover and address these disparities.

Uric acid drives acute kidney injury in tumor lysis syndrome (TLS). This study investigated the relationship between uric acid and changes in estimated glomerular filtration rate (eGFR) in adults at risk for TLS. Linear regression was used to evaluate the relationship between uric acid area under the curve (AUC) and percent change in eGFR from baseline at hospital dismissal, 1 and 3 months. In 210 included participants, each 100 mg*hour/dL increase in 24 h AUC was associated with an average decline in eGFR at hospital dismissal of 9% (95%CI 3, 15) in univariate analysis. Each 100 mg*hour/dL increase in 24 h AUC was independently associated with an average decline in eGFR of 8% (95%CI 2, 13) at 1 month after dismissal. Additional research is needed to confirm these findings and determine whether treatments that reduce overall uric acid exposure improve kidney outcomes. Preserving kidney health could favorably impact cancer treatment eligibility, tolerability, and outcomes.

The impact of body mass index (BMI) on survival in lymphoma remains controversial. We leveraged a prospective cohort of lymphoma patients enrolled to SPORE Molecular Epidemiology Resource between 2002 and 2015 to assess the association of BMI before diagnosis, BMI at diagnosis, and BMI change over time with lymphoma-specific survival (LSS). A total of 4009 lymphoma patients (670 diffuse large B-cell lymphoma (DLBCL), 689 follicular lymphoma (FL), 1018 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and 1632 other subtypes) were included. Significantly shorter LSS after diagnosis was observed for FL patients who were obese before diagnosis (HR: 3.02, 95%CI: 1.43-6.41, p =.004) and for those with a  ≥ 5% increase in BMI from diagnosis to 3-year follow-up (HR: 3.53, 95%CI: 1.22-10.2, p =.020). In contrast, obesity prior to or at the time of diagnosis was not associated with LSS in DLBCL and CLL/SLL. The impact of weight control after diagnosis in FL patient warrants investigation.

The impact of change in health behaviors (physical activity [PA], alcohol and smoking) on quality of life (QOL) in lymphoma survivors is not well understood. We evaluated the associations of health behaviors with QOL domains at diagnosis and at 3-year follow-up (FU3) in 2805 lymphoma survivors. We report clinically significant QOL score differences, defined as scores that exceeded a minimally important difference threshold and were statistically significant. Current smoking was associated with lower QOL at baseline ( p  < 0.01) and at FU3 ( p  < 0.01). Meeting the American Cancer Society PA guidelines was associated with better functional wellbeing and overall QOL at FU3 ( p  < 0.01). An increase in PA from baseline to FU3 was associated with improvement in physical, functional wellbeing and overall QOL at FU3 compared to baseline ( p  < 0.01). Thus, QOL in lymphoma survivors is associated with their health behaviors and active interventions to promote positive lifestyle changes in lymphoma survivors are needed.

Waldenstrom macroglobulinemia (WM) has an annual incidence of 3-3.2 cases per million-person/year. National Cancer Data Base was used to identify newly diagnosed WM cases requiring initiation of therapy and their annual facility volume was used to divide the treatment facilities into four quartiles (Qs). Cox regression was used to analyze the association between facility volume and survival, adjusted by demographics, socioeconomic, geographic, comorbidity factors and year of diagnosis. A total of 3064 patients treated in 795 facilities were included. The unadjusted median overall survival (OS) by facility volume was: Q1:6.5 years (5-year OS 55%), Q2:7 years (5-year OS 60%), Q3:8 years (5-year OS 64%), and Q4: NR (5-year OS 71%), p  < 0.0001. Our results demonstrated that a volume-outcome relationship exists in WM and is an independent predictor of overall survival in addition to the established risk factors as age and disease severity.

The aim is to prospectively evaluate the impact of a multidisciplinary lymphoma virtual tumor board. The utility of multi-site interactive lymphoma-specific tumor boards has not been reported. The Mayo Clinic Lymphoma Tumor Board is a component of the International Mayo Clinic Care Network (MCCN). The format includes the clinical case presentation, presentation of radiology and hematopathology findings by the appropriate subspecialist, proposed treatment options, review of the literature pertinent to the case, pharmacy contributions, and discussion followed by recommendations. Three hundred and nine consecutive highly selected real-time cases with a diagnosis of lymphoma were presented at the Mayo Clinic Lymphoma Tumor Board from January 2014 to June 2018 and decisions were prospectively tracked to assess its impact on the treatment decisions. A total of 309 cases were prospectively evaluated. One hundred and forty (45.3%) cases had some changes made or recommended. The total changes suggested were 179, as some cases had more than one recommendation. There were 93 (30%) clinical management recommendations, 45 (14.6%) additional testing recommendations, 29 (9.4%) pathology changes, and 6 (1.9%) radiology changes. In an electronic evaluation process, 93% of the responders reported an improvement in knowledge and competence, and 100% recommended no change in format of the board. A multidisciplinary lymphoma tumor board approach was found to have a meaningful impact on lymphoma patients while enhancing interdisciplinary interactions and education for multiple levels of the clinical care team.

One-in-five Hodgkin Lymphoma (HL) patients treated with bleomycin develop bleomycin pulmonary toxicity (BPT). Given bleomycin-omission data with negative interim-PET, we assessed changes in BPT statistics. We retrospectively evaluated 126 ABVD-treated HL patients for overall survival (OS), progression-free survival (PFS), BPT factors, and management. Forty-seven patients developed BPT with 17% BPT-mortality. In univariable analysis, OS was negatively impacted by BPT (HR = 3.6, 95%CI = 1.2-10.6), but not bleomycin-omission (HR = 1.3, 95%CI = 0.5-3.7). In multivariable analysis, BPT was not associated with OS (HR = 3.0, 95%CI = 0.9-9.9). BPT patients were older (46 y vs 33 years) and received less bleomycin (107 vs 215 units) compared to non-BPT patients. BPT was managed primarily with bleomycin-omission. "Recent Era" patients had lower BPT rates (28% vs 48%), mortality (10% vs 21%), and bleomycin doses (7 vs 12 doses), yet higher bleomycin-omission in the absence of the BPT (59% vs 8%) compared to "Early Era". Our data suggest BPT continually impacts OS in ABVD-treated HL patients, however management is changing.

Residual mediastinal FDG-uptake after frontline therapy for classical Hodgkin lymphoma (cHL) may constitute persistent disease or inflammatory changes. We analyzed practice patterns at two institutions to determine how often a mediastinal biopsy influenced patient management and outcome. Forty-two cases were eligible for review, mostly treated with ABVD. Twenty (group1) underwent a mediastinal biopsy and 22 did not (group2). In group1, 10/20 were positive for cHL and proceeded to salvage therapy (ST); 4/10 biopsy-negative patients were observed, and 6/10 received consolidative radiotherapy. Ten of 22 patients from group 2 were observed, 12/22 received ST. Ten of 14 observed patients remained PET-positive and 8/8 biopsies in these patients showed cHL. Deauville score (DS) 5 was associated with a positive biopsy (10/16). No overall survival difference between groups was observed. We conclude that observation and repeat a FDG-PET is reasonable for DS3-4 while for DS5, ST should be considered pending biopsy confirmation when feasible.

Early administration of rasburicase to enhance uric acid (UA) elimination has been adopted without robust evidence in support of its impact on clinical outcomes in tumor lysis syndrome (TLS), specifically, the prevention of acute kidney injury (AKI). This was a retrospective cohort study of adult lymphoma patients at intermediate or high risk for TLS. Excluded patients had AKI or were on dialysis at hospital admission. The incidence of new AKI in the setting of TLS was described along with predictors of its development, including early rasburicase use. In 383 included patients, the incidence of new-onset AKI during hospitalization was 6%. Predictors included age, history of renal or cardiovascular disease, and UA >8 mg/dL. Rasburicase use did not significantly impact the risk of developing AKI (HR 2.3; p  = .11). The UA level at the time of administration did not modify the effect of rasburicase on prevention of AKI ( p  = .36 for the interaction term).

Cryptococcosis is a rare opportunistic infection increasingly associated with lymphoproliferative disorders. The clinical course and outcomes in these patients have not been extensively studied. We retrospectively reviewed charts of adult patients with lymphoproliferative disorders diagnosed with cryptococcal infections. A total of 34 patients were identified; 31 (91%) had a B-cell neoplasm and 3 (9%) had a T-cell neoplasm. The most frequent clinical syndrome was disseminated cryptococcal infection (38%), followed by pneumonia (29%). 74% received prior chemotherapy and the overall mortality in this group was nearly six-fold higher than chemotherapy naïve patients; 26% were chemotherapy naïve. After a median follow-up of nine months from the date of infection, 24 patients had died (71%). The overall mortality at 30-days and one year was 18% and 46%, respectively. The high mortality warrants future studies to identify those at highest risk. Clinicians should remain vigilant as early diagnosis and treatment are of utmost importance.

In this phase 2 trial, we sought to evaluate the efficacy and safety of rituximab, cyclophosphamide, bortezomib, and dexamethasone (R-CyBorD) in patients with low-grade NHL. The regimen included rituximab on day 1 with weekly cyclophosphamide, dexamethasone, and bortezomib 1.3 mg/m 2 IV in a 28-day cycle. Twenty one patients were enrolled on the study. Median age was 69 years (range 51-80) and 17 (81%) patients had two or more prior treatments. Histologies included FL (n = 8), MCL (n = 8), and LPL/WM (n = 5). Hematologic toxicity and peripheral sensory neuropathy were the most common adverse events. With a median follow-up of 38.1 months, ORR was 13/21 (62%), with 4 (19%) CR. The ORR was 7/8 (88%) in FL and was 4/5 (80%) in LPL/WM. Median PFS and OS were 11.6 months and 54.8 months, respectively. R-CyBorD is an effective regimen in relapsed FL and LPL/WM patients with an acceptable safety profile.

Staging of peripheral T-cell non-Hodgkin lymphoma (PTCL) is determined by 18-F FDG PET scan and bone marrow biopsy. This study addressed the accuracy of PET at detecting bone marrow (BM) involvement at restaging in patients with known involvement pretreatment. We identified patients with biopsy proven BM PTCL at diagnosis and concomitant BM and PET at the end of therapy. Pre-treatment PET demonstrated 50% (8/16) had a false-negative PET scan of the BM. After induction, repeat biopsy revealed 62.5% (10/16) with BM involvement. Of these 10, two had a positive PET; eight were false negative by PET. Of the six patients with a negative posttherapy BM biopsy, four were PET negative and two false positive. The sensitivity of PET at end of treatment was 20% (2/10) with a specificity of 66.7% (4/6). PET/CT is not an accurate predictor of BM involvement in patients with known PTCL in the marrow.

Patterns of myeloid growth factor (GF) usage and febrile neutropenia (FN) were examined in patients >60 years of age with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) enrolled on CALGB 9793/ECOG-SWOG 4494, receiving initial therapy with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or rituximab + CHOP (R-CHOP). Myeloid GFs were administered to 256/520 (49%) patients. Indications for use were: prevent dose reduction/dose delay (81%, 207/256); treat FN or non-febrile neutropenia (NFN) (19%, 48/256). One or more FN episodes occurred in 41% (212/520) of patients, with FN most often in cycle 1 (38% of episodes). In multivariate analysis, risk factors for FN included age >65 years (odds ratio (OR) = 2.6, 95% CI: [1.4, 4.9]) and anemia (hemoglobin <12 g/dl) (OR =2.2, 95% confidence intervals (CI): [1.4, 3.5]. Myeloid GF use was common in this older DLBCL population receiving CHOP-based therapy, as was FN, especially during cycle one. Risk factors predictive for FN should be used prospectively to identify patients for whom myeloid GFs are best utilized.

The natural history of limited-stage peripheral T-cell lymphoma (PTCL) remains poorly defined. Therefore, we examined outcomes in patients with the most common PTCL subtypes (PTCL, not otherwise specified [PTCL, NOS], angioimmunoblastic T-cell lymphoma [AITL], anaplastic large cell lymphoma [ALCL]) and limited-stage disease. In this retrospective, multicenter study, 75 patients with limited-stage disease were identified. The median event-free survival (EFS) and overall survival (OS) observed were 2.1 and 6.5 years, respectively. In a landmark analysis excluding patients with primary refractory disease, no significant benefit was observed for patients undergoing consolidative radiation therapy. With the exception of patients undergoing salvage hematopoietic stem cell transplant, survival following disease relapse or progression was poor, thus highlighting the need for improved therapeutic strategies.

There are few studies examining complementary and alternative medicine (CAM) use and beliefs among non-Hodgkin lymphoma (NHL) survivors. Seven hundred and nineteen patients with NHL from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource who completed the 3-year post-diagnosis questionnaire were included in this study. Altogether 636 (89%) reported ever using CAM, with 78% utilizing vitamins, 54% alternative therapies and 45% herbals. Female gender was associated with increased overall CAM use (p=0.0001) as well as use of vitamins (p=0.0001), herbals (p=0.006) and alternative therapy (p=0.0002) for cancer. Older age (>60) was associated with increased vitamin use (p=0.005) and decreased herbal use (p=0.008). Among users, 143 (20%) believed CAM assists healing, 123 (17%) believed CAM relieves symptoms, 122 (17%) believed CAM gives a feeling of control, 110 (15%) believed CAM assists other treatments, 108 (15%) believed CAM boosts immunity, 26 (4%) believed CAM cures cancer and 36 (5%) believed CAM prevents the spread of cancer.

The optimal treatment of follicular lymphoma (FL) is not established. Rituximab's value potentially dilutes the impact of chemotherapy on FL. We reviewed 337 cases of FL treated initially with rituximab as monotherapy or with chemotherapy at the University of Iowa/Mayo Clinic from 2002 to 2009, investigating the association between chemotherapy delivery of cyclophosphamide or doxorubicin and survival. With median follow-up duration of 52.7 months, event-free survival (EFS) and overall survival (OS) were similar between the two groups, with a trend toward better EFS in the R-chemotherapy cohort (hazard ratio [HR]=1.24, p=0.28). In the R-chemotherapy group, increased total dose delivery and delivered dose intensity of doxorubicin were associated with improved EFS only in patients who did not receive R-maintenance (HR=0.81; p=0.02 and HR=0.94; p=0.04). Cyclophosphamide delivery was not associated with EFS. Thus, in the immunochemotherapy era, chemotherapy delivery strategy requires re-evaluation.

A limitation of the prognostic factor peripheral blood absolute lymphocyte/monocyte ratio (ALC/AMC) at diagnosis in diffuse large B-cell lymphoma (DLBCL) is its inability to sequentially assess the host/tumor microenvironment interaction and clinical outcomes during treatment. Therefore, we studied the ALC/AMC ratio at each rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) cycle as a predictor for survival. We studied 107 consecutive patients with DLBCL diagnosed, treated only with R-CHOP and followed at the Mayo Clinic. Unsupervised hierarchical clustering identified four clusters based on the patterns of ALC/AMC ratio recovery during cycles. The most inferior survival was seen in the cluster with ALC/AMC ratio < 1.1 in all cycles. By multivariate analysis, ALC/AMC ratio < 1.1 during all cycles was an independent predictor for inferior overall survival and progression-free survival. The ALC/AMC ratio during R-CHOP cycles predicts survival and provides a platform to develop therapeutic modalities to manipulate the ALC/AMC ratio during R-CHOP cycles to improve DLBCL clinical outcomes.

Peripheral T-cell lymphoma (PTCL) and natural killer (NK) cell lymphoma have poor survival with conventional cytotoxic chemotherapy. Because angiogenesis plays an important role in the biology of PTCL, a fully humanized anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab (A), was studied in combination with standard cyclosphosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy (ACHOP) to evaluate its potential to improve outcome in these patients. Patients were treated with 6-8 cycles of ACHOP followed by eight doses of maintenance A (15 mg/kg every 21 days). Forty-six patients were enrolled on this phase 2 study from July 2006 through March 2009. Forty-four patients were evaluable for toxicity and 39 were evaluable for response, progression and survival. A total of 324 cycles (range: 2-16, median 7) were administered to 39 evaluable patients and only nine completed all planned treatment. The overall response rate was 90% with 19 (49%) complete response/complete response unconfirmed (CR/CRu) and 16 (41%) a partial response (PR). The 1-year progression-free survival (PFS) rate was 44% at a median follow-up of 3 years. The median PFS and overall survival (OS) rates were 7.7 and 22 months, respectively. Twenty-three patients died (21 from lymphoma, two while in remission). Grade 3 or 4 toxicities included febrile neutropenia (n = 8), anemia (n = 3), thrombocytopenia (n = 5), congestive heart failure (n = 4), venous thrombosis (n = 3), gastrointestinal hemorrhage/perforation (n = 2), infection (n = 8) and fatigue (n = 6). Despite a high overall response rate, the ACHOP regimen failed to result in durable remissions and was associated with significant toxicities. Studies of novel therapeutics are needed for this patient population, whose clinical outcome remains poor.

Quality of life (QoL) is an important outcome in patients with non-Hodgkin lymphoma (NHL). We assessed the validity of administering the Functional Assessment of Cancer Therapy - General (FACT-G) at 12-month intervals over 3 years in a longitudinal study of 611 prospectively enrolled, newly diagnosed patients with NHL. We evaluated corrected item-total correlation and percent missing to identify items that may be less useful in certain NHL patient subgroups. The FACT-G subscales and total score demonstrated good internal consistency reliability, convergent validity and known-groups validity. Most scores also demonstrated good responsiveness to change. Questions that could be problematic included GE3 (losing hope) and GP2 (nausea) for patients in remission, and GP5 (bothered by side effects) for patients being observed. Overall, the FACT-G was a valid measure for monitoring QoL over time in patients with NHL. However, sensitivity analyses based on subscale scoring that excludes potentially problematic items may be warranted.

The absolute monocyte/lymphocyte count prognostic score (AMC/ALC score) has not been directly compared with the cell of origin (COO) to predict overall survival (OS) and progression-free survival (PFS) in diffuse large B-cell lymphoma (DLBCL). Thus, we retrospectively examined a new cohort of 99 patients with DLBCL treated from 2008 to 2010, (1) to validate whether AMC/ALC score affects survival, (2) to investigate whether AMC/ALC score is independent of COO to predict survival and (3) to assess whether AMC/ALC score can further stratify clinical outcomes by COO. By univariate analysis, the AMC/ALC score was a predictor for OS and PFS. On multivariate analysis performed including the COO and the International Prognostic Index, AMC/ALC score remained an independent predictor for OS and PFS. The AMC/ALC score was able to further stratify DLBCL clinical outcomes by COO. The AMC/ALC score was independent of COO and added to its ability to identify patients with high-risk disease.

Both LMO2 (LIM domain only 2) mRNA and protein expression in diffuse large B-cell lymphoma (DLBCL) have been associated with superior survival. However, a role for germline genetic variation in LMO2 has not been previously reported. Immunohistochemistry (IHC) for LMO2 was conducted on tumor tissue from diagnostic biopsies, and 20 tag single nucleotide polymorphisms (SNPs) from LMO2 were genotyped from germline DNA. LMO2 IHC positivity was associated with superior survival (hazard ratio [HR] = 0.55; 95% confidence interval [CI] 0.31-0.97). Four LMO2 SNPs (rs10836127, rs941940, rs750781, rs1885524) were associated with survival after adjusting for LMO2 IHC and clinical factors (p < 0.05), and one of these SNPs (rs941940) was also associated with IHC positivity (p = 0.02). Compared to a model with clinical factors only (c-statistic = 0.676), adding the four SNPs (c-statistic = 0.751) or LMO2 IHC (c-statistic = 0.691) increased the predictive ability of the model, while inclusion of all three factors (c-statistic = 0.754) did not meaningfully add predictive ability above a model with clinical factors and the four SNPs. In conclusion, germline genetic variation in LMO2 was associated with DLBCL prognosis and provided slightly stronger predictive ability relative to LMO2 IHC status.

The purpose of this study was to determine the activity of topotecan given by 21-day continuous infusion in patients previously treated with one prior therapy for a diffuse large-cell lymphoma or immunoblastic lymphoma. Patients with appropriate histology and measurable disease who had been treated with one prior chemotherapy regimen were eligible for study. Slides of tumor biopsies were submitted for central review of pathology. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 and adequate bone marrow function. Patients were treated with continuous infusion topotecan, 0.4 mg/m(2)/day × 21 days. Therapy could be escalated to 0.5 and then 0.6 mg/m(2)/day in subsequent cycles if there was no dose-limiting toxicity at the initial dose level. Patients were treated with two cycles after achieving a complete response or until disease progression or unacceptable toxicity occurred. Thirty-seven patients were enrolled. However, only 26 cases were eligible due to a performance status of > 2 (n = 2), more than one prior chemotherapy (n = 1) and wrong histology on review (n = 8). Due to the unexpectedly high ineligibility rate, two sets of analysis were done for all 37 patients enrolled and for the 26 eligible patients, respectively. Of the 37 patients (15 males and 22 females), the International Prognostic Index included 11% low risk, 30% low intermediate risk, 46% high intermediate risk and 8% high risk. The median follow-up was 77 months. A total of 136 cycles of therapy were given with a median of 3 cycles per patient. Grade 4 toxicities included: 14% grade 4 thrombocytopenia; 14% grade 4 granulocytopenia, 8% leukopenia, 3% each anemia, hemorrhage, infection, vomiting, thrombosis, liver toxicity and neuromotor toxicity. The response analysis including all 37 patients showed five complete responses (CRs) and four partial responses (PRs) for a total response rate of 24% (90% two-stage confidence interval 13-39%). Median progression-free survival (PFS) was 3.7 months, with 1- and 2-year PFS of 21% and 6%, respectively (90% confidence interval 11-34% and 2-15%). Median overall survival (OS) was 10.5 months, with 1- and 2-year OS of 41% and 27%, respectively (90% confidence interval 27-53% and 16-39%). Analysis including only eligible patients showed similar response rates and survival outcomes. Single agent topotecan has moderate activity for previously treated high-grade lymphoma equivalent to that of several newer agents, and should be considered for incorporation into multi-drug salvage chemotherapy programs.

Follicular lymphoma is characterized by a highly variable clinical course ranging from early transformation and disease-related mortality to prolonged periods of disease stability or even spontaneous remissions. This clinical heterogeneity is likely explained by differences in the tumor microenvironment, including variable infiltration by monocyte-derived cells. Therefore, we examined the absolute monocyte count obtained from a standard complete blood count with differential at the time of diagnosis as a prognostic factor in a cohort of patients with follicular lymphoma (n = 355) treated at a single institution between 1998 and 2007. We found that the absolute monocyte count at diagnosis is associated with overall survival, independent of the Follicular Lymphoma International Prognostic Index (FLIPI). Furthermore, the absolute monocyte count improved the ability to identify high-risk patients when used in conjunction with the FLIPI. These results further support the central role of non-neoplastic myeloid-lineage cells in follicular lymphoma biology.

The management of hairy cell leukemia has undergone historic unprecedented changes since three decades ago. This review summarizes treatment approaches utilized before the adenosine deaminase inhibitors. These historic approaches may still be utilized in patients with relapsed or refractory disease.

This study evaluates the predictive value of post-therapy 18-fluoro-deoxyglucose positron emission tomography (FDG-PET), including indeterminate studies, following curative-intent therapy in diffuse large B-cell lymphoma (DLBCL). Consecutive patients from September 2002 to December 2005 were prospectively offered enrollment in an observational registry. Available FDG-PET reports after primary therapy were interpreted by hematologist-oncologists as positive, negative, or indeterminate. One hundred twenty-five patients with DLBCL had a median follow-up of 35.2 months. Ninety-three percent were treated with R-CHOP-like therapy. Twenty percent of PET reports were judged indeterminate. Event-free survival (EFS) at 3 years for the negative and indeterminate groups was 85% and 71%, respectively (p = 0.28 by log-rank). Overall survival (OS) at 3 years for negative, indeterminate, and positive groups was 89%, 88%, and 48%. Combining the pre-therapy International Prognostic Index (IPI) with the post-therapy FDG-PET result added to the predictive value of the study for patients. Three-year EFS for patients with low or low-intermediate IPI risk and an indeterminate FDG-PET report was 93%, while for those with high or high-intermediate pre-therapy IPI the 3-year EFS was 45% (p < 0.02). Interpreting FDG-PET reports following curative-intent chemotherapy in patients is informative but imprecise, and incorporation of pre-therapy prognosis can improve predictive utility.

DHAP (dexamethasone, cytosine arabinoside and cis-platinum) is a commonly used regimen for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The optimal treatment for patients who do not respond to DHAP, but are still potential candidates for autologous stem cell transplantation, is unclear. One option is to proceed with an alternative chemotherapy regimen such as ifosfamide, carboplatin, and etoposide (ICE). The overall response rate (ORR) and overall survival (OS) associated with this chemotherapy sequence is unknown. Patients with DLBCL receiving DHAP as the first salvage therapy without response followed by ICE as second salvage were studied to learn the ORR to ICE and OS. The ORR to ICE in these DHAP-failures was 52% (11/21) with 14% (3/21) complete responses and 38% (8/21) partial responses. Nine patients (43%) were able to proceed to transplant and 29% (6/21) are long-term survivors. In patients with stable disease after DHAP the ORR was 67% (8/12) with 42% (5/12) becoming long-term survivors. In contrast, only 33% (3/9) of patients who had progressive disease on DHAP responded to ICE with only one patient achieving a durable response. Patients with stable disease after DHAP can be salvaged with ICE-based chemotherapy regimens whereas patients who progress on DHAP have a poor outcome. Patients with progressive disease on DHAP should be considered for alternative salvage regimens or experimental therapy.

Histological transformation of low-grade non-Hodgkin lymphoma (NHL) to diffuse large cell NHL is well recognized and is associated with a poor prognosis. We sought to determine the overall outcome and the factors that affect survival in patients with histological transformation of low-grade NHL. Between November 1979 and September 2000, 93 patients who developed transformed lymphoma were identified. The median time to transformation was 4.2 years from the original diagnosis. The median age at transformation was 63 years. Seventy-eight percent had stage III or IV disease. Fifty-seven percent had extranodal involvement, including bone marrow; 33% had an elevated lactate dehydrogenase. The International Prognostic Index (IPI) at transformation was termed the transformation IPI (tIPI); 29% had a tIPI of 0-1, 59% had a tIPI of 2-3 and 8% had a tIPI of 4-5. At a median follow-up of 15 months from histological transformation, 20 of 93 patients (22%) were alive. The median survival from transformation was 15 months (4 months to 19.7 years). On univariate analysis, the following factors at the time of histological transformation were associated with an improved survival: low tIPI (P = 0.009), time to transformation > 4 years (P = 0.02), age < or = 60 years (P = 0.02) and stage I or II disease (P = 0.04). On multivariate analysis, factors that remained significant included a low tIPI (P = 0.0001) and a time to transformation > 4 years (P = 0.004). tIPI correlated with overall survival (OS); IPI 0-1, median OS 38 months; IPI 2-3, median OS 12 months; IPI 4-5, median OS 4 months. In conclusion, tIPI at the time of histological transformation is an important predictor of OS. A time to transformation > 4 years from diagnosis is associated with better OS.

To assess the effect of rituximab therapy and other prognostic factors on overall survival in patients with post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation, 30 consecutive patients diagnosed with PTLD between 1999 and 2002 were analyzed. Fifteen (50%) patients received rituximab (375 mg/m(2) once a week). Fifteen (50%) patients had other interventions including observation, immunosuppression reduction, surgery, chemotherapy, radiation or a combination of these. Patients receiving rituximab vs. non-rituximab differed in the following variables: age at diagnosis of PTLD (P = 0.009), days to PTLD (P = 0.0005), Epstein-Barr virus (EBV) in situ hybridization status (P = 0.02) and CD20-positive status (P = 0.006). At the time of last follow-up, 10 (33%) patients in the rituximab group and 5 (17%) in the non-rituximab group were alive. On univariate analysis for overall survival of all 30 patients, the significant factors were: treatment with rituximab (P = 0.03), response to treatment (P = 0.005), CD20 positive (P = 0.0004), low international prognostic index (IPI; P = 0.02) and good performance status (P = 0.009). Multivariate analysis of all patients was significant for CD20-positive status (P = 0.0007) and low performance status (P = 0.006). On multivariate analysis for overall survival in patients with CD20-positive PTLD, low IPI (P = 0.004) and rituximab therapy (P = 0.03) were significant. Low IPI and rituximab therapy led to an improved overall survival in patients with CD20-positive PTLD.

There are few data on the clinical characteristics of familial vs. sporadic non-Hodgkin lymphoma (NHL). Using the NHL registry at the Mayo Clinic, we compared age of diagnosis, gender, tumor site and histologic subtype between patients with sporadic and familial NHL. In 2001, we identified all new cases of adult NHL diagnosed between 1986 and 2000 in the Mayo Clinic NHL database (n = 2289) and mailed out a family history questionnaire to all living patients with a current address (n = 1043). Each NHL patient was categorized according to their self-report of leukemia or lymphoma in first-degree (1 degree) relatives. We received complete FH information on 740 patients (71%). Age at diagnosis of NHL ranged from 18-88 years (mean = 59 years) and 53% of our cases were male. First-degree FH of lymphoma was reported by 43 patients (6%), 1 degree FH of leukemia by 27 patients (4%) and 1 degree FH of both in 4 (1%). There was a nonstatistically significant later age at diagnosis for cases with any family history of lymphoma or leukemia (mean age = 61.3 and 61.7 years, respectively) vs. no family history (59.0 years) (P = 0.58). The male to female ratio for those with a FH of leukemia (ratio = 2.9) was higher compared to those with FH lymphoma (0.95) or no FH (1.1) (P = 0.08). No differences were apparent between 1 degree FH and site of NHL (nodal vs. extranodal) (P = 0.53). Among recently diagnosed cases (since 1995), there was some suggestion of a greater proportion of aggressive tumors for those with any family history (69% and 55%) vs. none (50%) (P = 0.20). We found little evidence of large differences between familial and sporadic NHL with regard to age, gender, site or histologic subtype.