Racial and Ethnic Characteristics and Outcomes of Patients Diagnosed with CLL/SLL in the USA.

INTRODUCTION: This study was designed to compare outcomes among patients by race and ethnicity in the post-covalent Bruton tyrosine kinase inhibitor (cBTKi) treatment era. METHODS: A nationwide electronic health record (EHR)-derived de-identified database was utilized that included patients diagnosed with CLL from 2013 to 2022 who received systemic therapy for their disease. Use of cBTKi therapy, time to next treatment or death (TTNT-D), and overall survival (OS) were compared by race in unadjusted (Kaplan-Meier method) and adjusted analyses (Cox proportional hazards regression). RESULTS: This study included 4,572 White (71.8%) and 558 Black (8.8%) patients with CLL; 270 were Hispanic or Latino (4.2%). Patients who were Black were significantly younger, more were female, had later stage disease, were of lower socioeconomic status (SES), and were more likely to have unmutated immunoglobulin heavy chain gene (IGHV) and to have received cBTKi therapy than White patients (all p ≤ 0.002). SES was also significantly different by ethnicity. TTNT-D and OS were not different by race in either unadjusted or adjusted analyses (all p > 0.05). CONCLUSION: In unadjusted and adjusted analyses, TTNT-D and OS were not different by race. These data did not identify racial healthcare disparities in the era following the introduction of cBTKi therapy despite differences in baseline characteristics.

EUS-guided biopsy for the diagnosis and classification of lymphoma.

BACKGROUND: EUS-guided FNA and Tru-cut biopsy (TCB) is highly accurate in the diagnosis of lymphoma. Subclassification, however, may be difficult in low-grade non-Hodgkin lymphoma and Hodgkin lymphoma. OBJECTIVE: To determine the yield of EUS-guided biopsy to classify lymphoma based on the World Health Organization classification of tumors of hematopoietic lymphoid tissues. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A total of 24 patients referred for EUS-guided biopsy who had a final diagnosis of lymphoma or "highly suspicious for lymphoma." INTERVENTIONS: EUS-guided FNA and TCB combined with flow cytometry (FC) analysis. MAIN OUTCOMES MEASUREMENT: Lymphoma subclassification accuracy of EUS guided biopsy. RESULTS: Twenty-four patients were included in this study. Twenty-three patients underwent EUS-FNA, and 1 patient had only TCB. Twenty-two underwent EUS-TCB combined with FNA. EUS correctly diagnosed lymphoma in 19 out of 24 patients (79%), and subclassification was determined in 16 patients (66.6%). Flow cytometry correctly identified B-cell monoclonality in 95% (18 out of 19). In 1 patient diagnosed as having marginal-zone lymphoma by EUS-FNA/FC only, the diagnosis was changed to hairy cell leukemia after a bone marrow biopsy was obtained. EUS had a lower yield in nonlarge B-cell lymphoma (only 9 out of 15 cases [60%]) compared with large B-cell lymphoma (78%; P = .3 [Fisher exact test]). LIMITATIONS: Retrospective, small number of patients. CONCLUSION: EUS-guided biopsy has a lower yield to correctly classify Hodgkin lymphoma and low-grade lymphoma compared with high-grade diffuse large B-cell lymphoma.

Cord blood transplantation: evolving strategies to improve engraftment and immune reconstitution.

PURPOSE OF REVIEW: For many patients with relapsed or high-risk hematologic malignancies, allogeneic stem cell transplantation offers the best hope for cure. For patients lacking a suitable family or unrelated donor, umbilical cord blood provides a promising alternative graft source. Dramatic advances in cord blood transplantation (CBT) have been made in the past 2 decades, leading to a rapid expansion of CBT programs worldwide. RECENT FINDINGS: Promising new strategies, including double CBT and ex-vivo graft engineering, have improved myeloid and platelet engraftment rates and kinetics. However, delayed immune reconstitution and associated infectious morbidity and mortality remain a significant challenge, especially in adult CBT recipients. In adults, both impaired recipient thymopoiesis and the lack of transferred memory cells contribute to delayed T cell recovery, resulting in an increased risk of opportunistic infections. SUMMARY: Novel clinical approaches in CBT have improved outcomes, especially those associated with delays in myeloid and platelet engraftment. However, delayed immune reconstitution remains a great challenge. Novel strategies, including graft engineering approaches capable of improving T cell recovery, and pharmacologic interventions capable of preserving thymopoiesis and facilitating the recovery of a diverse functional T cell repertoire are being pursued; these approaches have great potential to further improve outcomes after CBT.

Successful pregnancy in a patient with chronic myeloid leukaemia exposed to dasatinib during the first trimester.

We report a case of a 25-year-old woman with chronic myeloid leukaemia who was randomised to dasatinib 100 mg orally daily in a clinical trial. The patient was advised to avoid pregnancy while on treatment due to its teratogenic potential. Five months later, the patient was found to be 6 weeks pregnant. Once pregnancy was confirmed, dasatinib was immediately stopped and the patient was taken off the trial. She was managed conservatively during the remainder of her pregnancy with close observation only. She delivered a healthy infant at 37 weeks' gestation without any documented birth defects. Dasatinib has been shown in animal studies to cause fetal toxicities, but the effect of exposure during conception and pregnancy in humans is not known. We provide a full report of a successful pregnancy in a patient who was exposed to dasatinib during the first trimester; we also give a brief literature review.

High rate and prolonged duration of complete remissions induced by rituximab, methotrexate, doxorubicin, cyclophosphamide, vincristine, ifosfamide, etoposide, cytarabine, and thalidomide (R-MACLO-IVAM-T), a modification of the National Cancer Institute 89-C-41 regimen, in patients with newly diagnosed mantle cell lymphoma.

Novel therapeutic approaches are needed in mantle cell lymphoma (MCL). We conducted a phase II study in MCL testing an intensive regimen, R-MACLO-IVAM-T, a modification of the NCI 89-C-41 protocol. Newly diagnosed patients were treated with rituximab, methotrexate, doxorubicin, cyclophosphamide, and vincristine (cycle 1) followed by rituximab, ifosfamide (and mesna), etoposide, and cytarabine (cycle 2). These two cycles were repeated once, and patients achieving complete response (CR) received maintenance thalidomide. Among the 22 patients enrolled, 21 completed two or more cycles and achieved a CR. Three patients relapsed, while 17 are alive and relapse-free after a median follow-up of 37 months (range 19-65 months). Two patients died: one from sepsis during cycle 1 and another at 38 months while in remission from MCL. The progression-free survival at 3 years was 78% (95% CI: 51-91%). These results compare favorably with previously reported outcomes suggesting that durable remissions can be achieved without myeloablative therapy.

[18F]-fluorodeoxyglucose positron emission tomography combined with computed tomography detection of asymptomatic late pulmonary toxicity in patients with non-Hodgkin lymphoma treated with rituximab-containing chemotherapy.

Rituximab is a chimeric anti-CD20 monoclonal antibody widely used in the treatment of B-cell non-Hodgkin lymphomas (NHL). Most adverse effects are due to infusion-related reactions, and severe respiratory complications are rare. We retrospectively reviewed clinical data and serial imaging studies of five patients with NHL treated with rituximab-containing chemotherapy who developed new pulmonary abnormalities on routine follow-up FDG-PET/CT imaging. None of the patients had pulmonary lymphoma or other pulmonary disease before therapy and all remained asymptomatic during follow-up. New pulmonary interstitial FDG-uptake was detected on follow-up FDG-PET/CT between 1 and 3 months post-treatment, preceded computed tomography abnormalities in one case, and persisted for several months. FDG uptake was linear, subpleural with maximum Standardized uptake value (SUV) from 2.0 to 5.84. Rituximab-containing chemotherapy for NHL may be associated with asymptomatic late pulmonary toxicity characterised by a distinct FDG uptake pattern. Awareness of this finding is important and should not be confused with lymphoma.

Pharmacotherapy of large B-cell lymphoma.

BACKGROUND: Constituting approximately 30% of lymphoid malignancies, diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma in adults worldwide. The clinical and biologic heterogeneity that exists in DLBCL suggests that this entity might actually be comprised of several distinct neoplasms that could require different therapeutic approaches. DLBCL was considered incurable until combination chemotherapy became available. OBJECTIVE: Current treatment strategies for the treatment of untreated and relapsed advanced-stage DLBCL are reviewed; novel treatments for DLBCL are discussed. METHODS: Relevant literature was identified using the PubMed search engine and by reviewing abstracts from major conference proceedings. RESULTS/CONCLUSION: Recently, novel therapeutic strategies, including the incorporation of immunotherapy to combination chemotherapy, have improved outcome for patients with DLBCL with cure rates exceeding 50%, especially in younger patients.

Prognostic factors and treatment of patients with T-cell non-Hodgkin lymphoma: the M. D. Anderson Cancer Center experience.

BACKGROUND: T-cell non-Hodgkin lymphomas (T-NHL) are more aggressive and patients have a poorer prognosis compared with patients with the corresponding B-cell lymphomas. Although intensive treatments have been developed, it is unknown whether they are more effective than CHOP chemotherapy (cyclophosphamide, doxorubicin, oncovorin, and prednisone). METHODS: The authors' retrospective study evaluated the clinical outcome of 135 previously untreated patients with T-NHL who were treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between 1996 and 2002. Lymphomas with T-cell histologies with the exception of mycosis fungoides were included. RESULTS: The estimated median overall survival was 46 months. Thirty-seven percent of the patients received CHOP therapy, 48% received intensive therapy, and 15% received other therapy. The estimated 3-year overall survival rates were 62% for the patients treated with CHOP therapy and 56% for the patients who received intensive therapy. After the exclusion of patients with anaplastic large cell lymphoma (ALCL), who are known to have a better prognosis than patients with other T-NHLs, the estimated 3-year overall survival rates were 43% for the patients treated with CHOP therapy and 49% for the patients who received intensive therapy. Parameters that may be independent prognostic factors for survival in T-NHL, excluding ALCL, included ECOG performance status > or = 2, beta-2-microglobulin level > 2 mg/L, lactate dehydrogenase level higher than normal, bulky disease > or = 7 cm, and a higher international prognostic index and tumor score. CONCLUSIONS: The current study data suggested that patients treated with intensive therapies did not fare better than those treated with CHOP therapy. New treatment regimens need to be developed for patients with T-NHL.

Nonmyeloablative allogeneic hematopoietic transplantation: a promising salvage therapy for patients with non-Hodgkin's lymphoma whose disease has failed a prior autologous transplantation.

PURPOSE: Allogeneic transplantation for patients with lymphoma who experience a recurrence after an autologous transplantation has been considered a hazardous therapeutic choice. We investigated the safety and efficacy of nonmyeloablative stem-cell transplantation in these patients. PATIENTS AND METHODS: Patients were required to have chemosensitive or stable disease. Twenty consecutive patients were treated in two sequential trials. Fifteen patients underwent a preparative regimen of fludarabine (30 mg/m(2) daily for 3 days), intravenous cyclophosphamide (750 mg/m(2) daily for 3 days), and rituximab. For the remaining five patients, the conditioning regimen consisted of cisplatin (25 mg/m(2) continuous infusion daily for 4 days), fludarabine (30 mg/m(2) daily for 2 days), and cytarabine (1,000 mg/m(2) daily for 2 days). Tacrolimus and methotrexate were used for graft-versus-host disease prophylaxis. RESULTS: All patients experienced engraftment of donor cells. One patient (5%) experienced grade 2 acute graft-versus-host disease, and no patients experienced a higher grade. One patient experienced disease progression at 115 days post-transplantation and responded to donor lymphocyte infusion. The remaining patients remained disease-free. One patient died at 10.5 months from a fungal infection. With a median follow-up time of 25 months, the estimated 3-year current progression-free survival rate was 95%. CONCLUSION: These data suggest that nonmyeloablative allogeneic stem-cell transplantation is an effective option in lymphoma patients with chemosensitive or stable disease who experience disease recurrence following autologous transplantation.