PET/CT in leukemia: utility and future directions.

2-Deoxy-2-[ 18 F]fluoro- d -glucose PET/computed tomography ([ 18 F]FDG PET/CT) has proven to be a sensitive method for the detection and evaluation of hematologic malignancies, especially lymphoma. The increasing incidence and mortality rates of leukemia have raised significant concerns. Through the utilization of whole-body imaging, [ 18 F]FDG PET/CT provides a thorough assessment of the entire bone marrow, complementing the limited insights provided by biopsy samples. In this regard, [ 18 F]FDG PET/CT has the ability to assess diverse types of leukemia The utilization of [ 18 F]FDG PET/CT has been found to be effective in evaluating leukemia spread beyond the bone marrow, tracking disease relapse, identifying Richter's transformation, and assessing the inflammatory activity associated with acute graft versus host disease. However, its role in various clinical scenarios in leukemia remains unacknowledged. Despite their less common use, some novel PET/CT radiotracers are being researched for potential use in specific scenarios in leukemia patients. Therefore, the objectives of this review are to provide a thorough assessment of the current applications of [ 18 F]FDG PET/CT in the staging and monitoring of leukemia patients, as well as the potential for an expanding role of PET/CT in leukemia patients.

Definition of bulky disease in early stage diffuse large B-cell lymphoma in computed tomography on coronal and transverse planes.

Background: In early stage diffuse large B-cell lymphoma (ESDLBL), tumor bulkiness is an important determinant of treatment and prognosis. Tumor bulk is usually measured on transverse computed tomography (CT) plane and variably defined from 5 to 10 cm. Objectives: Our study aims to investigate the prognostic significance of bulky disease measured on CT coronal and transverse planes and to evaluate the outcome of patients with bulky disease. Methods: Patients with ESDLBL and treated with rituximab, cyclophosphamide, doxorubicin, and prednisolone (RCHOP) with or without radiotherapy were included. Receiver Operating Characteristic (ROC) analysis was used to identify the optimal tumor dimension that correlated with progression, relapse, or death. Correlation between different variables and progression-free survival (PFS) and overall survival (OS) were analyzed using log-rank (Mantel-Cox) test and Cox proportional hazard models. Results: A total of 127 patients with a median age of 47 (range: 18-90) years were included. Eighty-two (64.6%) patients treated with combined modality treatment (CMT) [RCHOP + radiotherapy]. After a median follow-up of 40 (range: 2-114) months, 3-year PFS and OS were 83.9% (95% CI: 76.759%-89.981%), and 80.6% (95% CI: 72.499%-87.531%), respectively. Tumor dimension of >7.5 cm measured on either CT plane was the optimal cutoff point to define bulky disease. Three-year PFS and OS were inferior in the group of patients with no bulky disease on transvers plane (n = 84) but had bulky disease on coronal plane (n = 9,10.7%); (94.2% vs. 75%, p = 0.017 and 90.5% vs. 56.3%, p = 0.002), as well as in patients with no bulky disease on coronal plane (n = 89), but had bulky disease on transverse plane (n = 14, 15.7%); (94.1% vs. 62.3%, p < 0.001, and 90.4% vs. 63.5%, p = 0.002). Compared to RCHOP alone, 3-year PFS and OS were better in patients with bulky disease treated with CMT (78% vs. 52.5%, p = 0.018 and 81.8% vs. 38.7%, p = 0.003) but not in patients with non-bulky disease (96.2% vs. 93%, p = 0.691 and 87.6% vs. 91.5%, p = 0.477). Conclusion: In ESDLBL, measurement of tumor mass on transverse and coronal CT planes may help in better identification of patients with bulky disease. The use of CMT was associated with better survival outcomes in patients with bulky disease.

Outcome and patterns of relapse in primary gastric diffuse large B cell lymphoma treated with RCHOP.

OBJECTIVES: Patterns and predictors of relapse in primary gastric diffuse large B cell lymphoma (DLBCL) were variably reported. Our study aims to evaluate the patterns and predictors of relapse in early-stage gastric DLBCL treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone (RCHOP). METHODS: From 2005 to 2019, the medical records of 72 patients with stage I or stage II gastric DLBCL treated with six cycles of RCHOP without radiotherapy were reviewed. Different variables were correlated with progression free survival (PFS), overall survival (OS), and local relapse free survival (LRFS). RESULTS: 64 (88.1%) patients achieved a complete response (CR), while 8 (11.9%) had refractory disease. After CR, 9 (14%) patients relapsed; 7 (78%) relapses were loco-regional. Abnormal LDH (p = 0.028), H. pylori negative (p = 0.032) and, stage adjusted international prognostic index (sa-IPI) > 1 (p = 0.013) correlated with loco-regional failure. The 5-year PFS, OS, and LRFS were 74.8%, 75.3%, and 87.5%, respectively, after a median follow-up of 58 (range: 6-185) months. The median time to progression or relapse was 9 months (range: 5-54 months). In multivariate analysis, a sa-IPI >1 (HR: 3.56, CI: 1.35-8.8, p = 0.01) was associated with PFS while low albumin (HR: 8.85, CI: 1.09-71.4, p = 0.041) was associated with worse OS. None of the variables were associated with LRFS. CONCLUSION: Treatment of primary gastric DLBCL with RCHOP results in a high CR rate. The majority of treatment failures were loco-regional. Sa-IPI and H. pylori status may be used to identify patients who may benefit from combined modality treatment.

Pembrolizumab for the Treatment of Relapsed and Refractory Classical Hodgkin Lymphoma After Autologous Transplant and in Transplant-Naïve Patients.

INTRODUCTION: Checkpoint inhibitors demonstrated significant efficacy in relapsed/refractory Hodgkin's Lymphoma (R/R cHL) resulting in high responses and prolonged progression free survival in patients, who relapse after or are ineligible for autologous stem cell transplantation (auto-SCT). We aimed to assess the efficacy and toxicity of Pembrolizumab before auto-SCT and in transplant naïve patients and calculate survival outcomes. PATIENTS AND METHODS: Fifty-five patients with R/R cHL were included. Patients demographics, including age, sex, risk stratification, therapy received and details pertaining transplantation, were collected. RESULTS: Median age was 28 years (range, 16-62 years). The median follow-up was 15.3 months and the median number of previous treatments was 3 (1-10). The best objective response was 74.5% (CR 32.7%, SD 5.5%) with reasonable safety profile. Twenty-nine of the responding patients received subsequent auto-SCT and 9 allogeneic stem cell transplantation (allo-SCT), 6 are currently alive with ongoing response. At the time of analysis, 6 patients remained on Pembrolizumab and the rest discontinued. The main reason for discontinuation was disease progression (n-49). Twelve-months overall survival and progression free survival (PFS) was 92% (95% CI: 76%-95%) and 51% (95% CI, 39%-67%) respectively. Twelve-month PFS for patients, who achieved CR or PR or PD was 88% (95% CI: 07%-75%); PR 60% (95% CI: 21%-29%) and 5% (95% CI: 5%-0%). Though the number of patients who received auto-SCT after Pembrolizumab was small (n-15), 12 months overall survival and PFS 100% and PFS 92%. 11 patients (20%) deceased during the follow-up and none was regarded to be treatment-related. CONCLUSION: Checkpoint inhibitors are effective in heavily pretreated cHL patients with reasonable survival outcomes. The results supporting the concept of auto and/or allo-SCT after checkpoint inhibitors use.

Treatment of adult Burkitt lymphoma with the CALGB 1002 protocol: a single center experience in Jordan.

BACKGROUND: The treatment of adult Burkitt lymphoma with pediatric-based chemotherapy protocols usually results in high cure rates, although with significant toxicity. We report our experience with the Cancer and Leukemia Group B1002 (CALGB 1002) protocol. METHODS: The files of adult patients diagnosed with Burkitt lymphoma and treated with the CALGB 1002 protocol at King Hussein Cancer Center between 2008 and 2017 were reviewed. Baseline demographics, clinical laboratory features, treatment details, and responses were collected. The correlations between clinical and laboratory variables with event-free survival (EFS) and overall survival (OS) were determined by univariate and multivariate analyses using backward stepwise Cox regression models. EFS and OS were plotted using Kaplan‒Meier curves. RESULTS: This study included 19 patients with a median age of 33 years (range, 19‒65). Eleven (58%) and two (10.5%) patients had advanced-stage and central nervous system disease, respectively. Among 106 administered cycles, the median interval between cycles was 23 days (range, 19‒84 days). Sixteen patients (84%) achieved a complete response. After a median follow-up of 40.8 months, the 3-year EFS and OS rates were 78.95%. Patients with a low-risk International Prognostic Index (IPI) had better survival than those with intermediate-or high-risk IPI. Grade III‒IV hematological toxicities occurred in 88% of patients, while 73% had grade III‒IV mucositis. CONCLUSION: In adult Burkitt lymphoma, the CALGB 1002 protocol provides high cure rates and can be administered promptly, but is associated with significant toxicity. Risk-adapted approaches and other, less toxic, chemotherapeutic regimens should be considered.

Kratom-Induced Liver Injury: A Case Series and Clinical Implications.

Drug-induced liver injury (DILI) is among the most common causes of acute liver injury and acute liver failure in the United States. Kratom is an herbal supplement made from the leaves of a tropical evergreen tree (Mitragyna speciosa) that is native to Southeast Asia. Due to its psychotropic and opioid-like activity, there has been an increase in its use as a recreational drug. Despite this increase, little is known regarding the toxicities and adverse effects though it is known to cause DILI. We present two cases of DILI associated with Kratom use.

Accelerated Phase of Myeloproliferative Neoplasms.

BACKGROUND: Myeloproliferative neoplasms (MPNs) can transform into blast phase MPN (leukemic transformation; MPN-BP), typically via accelerated phase MPN (MPN-AP), in ∼20-25% of the cases. MPN-AP and MPN-BP are characterized by 10-19% and ≥20% blasts, respectively. MPN-AP/BP portend a dismal prognosis with no established conventional treatment. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole modality associated with long-term survival. SUMMARY: MPN-AP/BP has a markedly different mutational profile from de novo acute myeloid leukemia (AML). In MPN-AP/BP, TP53 and IDH1/2 are more frequent, whereas FLT3 and DNMT3A are rare. Higher incidence of leukemic transformation has been associated with the most aggressive MPN subtype, myelofibrosis (MF); other risk factors for leukemic transformation include rising blast counts above 3-5%, advanced age, severe anemia, thrombocytopenia, leukocytosis, increasing bone marrow fibrosis, type 1 CALR-unmutated status, lack of driver mutations (negative for JAK2, CALR, or MPL genes), adverse cytogenetics, and acquisition of ≥2 high-molecular risk mutations (ASXL1, EZH2, IDH1/2, SRSF2, and U2AF1Q157). The aforementioned factors have been incorporated in several novel prognostic scoring systems for MF. Currently, elderly/unfit patients with MPN-AP/BP are treated with hypomethylating agents with/without ruxolitinib; these regimens appear to confer comparable benefit to intensive chemotherapy but with lower toxicity. Retrospective studies in patients who acquired actionable mutations during MPN-AP/BP showed positive outcomes with targeted AML treatments, such as IDH1/2 inhibitors, and require further evaluation in clinical trials. Key Messages: Therapy for MPN-AP patients represents an unmet medical need. MF patients, in particular, should be appropriately stratified regarding their prognosis and the risk for transformation. Higher-risk patients should be monitored regularly and treated prior to progression to MPN-BP. MPN-AP patients may be treated with hypomethylating agents alone or in combination with ruxolitinib; also, patients can be provided with the option to enroll in rationally designed clinical trials exploring combination regimens, including novel targeted drugs, with an ultimate goal to transition to transplant.

Amenorrhea, fertility preservation, and counseling among young women treated with anthracyclines and taxanes for early-stage breast cancer, a retrospective study.

Chemotherapy may cause ovarian toxicity and infertility. Cancer patients are usually overwhelmed, and focus exclusively on cancer diagnosis and may not pay attention to fertility-related issues. In this paper we look at the rate of amenorrhea and fertility counseling among such young patients.Premenopausal women with early-stage breast cancer treated with adjuvant or neoadjuvant chemotherapy were recruited. Amenorrhea was defined as absence of menstruation for ≥12 months after the completion of chemotherapy.A total of 94 patients met the eligibility criteria and were included in this analysis. Median age at diagnosis was 35.7 (range, 22-44) years. Seventy-nine (85.9%) respondents were counseled about amenorrhea and 37 (40.2%) were considering having children. Long-term amenorrhea was reported by 51 (54.3%) patients. The addition of taxanes to anthracyclines, in 2 different regimens, increased the risk of amenorrhea to 69.2% and 66.7% compared to 38.9% with anthracycline-alone, P < .0001. Longer duration of chemotherapy (≥24 weeks) might also be associated with higher rate of amenorrhea (67.7%) compared to 43.4% in those who had shorter duration (<24 weeks), P = .031.The addition of taxanes to anthracycline-based chemotherapy increased the risk of amenorrhea. However, shorter duration of chemotherapy, even with taxanes, may lower such risk. Our study highlights the importance of fertility counseling to improve fertility preservation rates. Given the importance of taxanes, shorter regimens are associated with lower amenorrhea rates and should be preferred over longer ones.

Myeloid sarcoma.

PURPOSE OF REVIEW: Myeloid sarcoma; also known as granulocytic sarcoma and chloroma, often occurs concomitantly with AML, and rarely without bone marrow involvement. In this article, we review the recent literature on myeloid sarcoma, focusing on treatment approach for this rare disease, and addressing the prognostic and therapeutic role of molecular and cytogenetic aberrations. RECENT FINDINGS: Molecular testing and cytogenetics are important adjunct to conventional diagnostic methods. The significance of cytogenetic and molecular abnormalities in myeloid sarcoma is not completely established, but testing for targetable mutations on myeloid sarcoma cells is feasible, imperative, and may guide treatment decisions. Outcomes in myeloid sarcoma largely depend on the background of its development. Almost all patients with myeloid sarcoma eventually develop AML typically in a short period after its diagnosis; therefore, remission induction treatment using AML type chemotherapy has been the standard of care. Postremission therapy is controversial; allogenic SCT, radiotherapy or consolidation chemotherapy should be considered according to patient risk. SUMMARY: Further research is required to understand the nature of myeloid sarcoma, and inclusion of patients with this condition in clinical trials should be considered to better identify the best diagnostic, prognostic, and therapeutic approach in managing this rare disease.