Lymphoid Malignancies In Patients Research Articles

Incidence of lymphoid malignancies in patients with lymphocytosis identified by general practitioners

Incidence of lymphoid malignancies in patients with lymphocytosis identified by general practitioners

Treatment of lymphoid malignancies in patients with primary immunodeficiencies associated with DNA repair defects

Nijmegen breakage syndrome (NBS) and ataxia-telangiectasia (AT; Louis–Bar syndrome) are primary immunodeficiencies (PID) associated with chromosome instability and DNA repair defects that predispose individuals to an increased risk of various malignancies. In our study, we retrospectively analyzed clinical characteristics and outcomes of 28 cancer cases in 14 patients with AT and 10 patients with NBS who had been treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology between January 2007 and December 2022. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The most common type of malignancy was mature B-cell non-Hodgkin lymphoma (B-NHL) (42%), with diffuse large B-cell lymphoma (DLBCL) accounting for 91% of all B-NHL cases. Other cases included T-cell acute lymphoblastic leukemia (ALL) (n = 3), B-cell ALL (n = 2), Hodgkin lymphoma (n = 3), NK/T-cell lymphoma (n = 1), T-cell lymphoblastic lymphoma (n = 1), peripheral T- cell lymphoma (n = 2), medulloblastoma (n = 1) epithelioid rhabdomyosarcoma (n = 1), T-cell prolymphocytic leukemia (n = 2). A total of 4 patients were diagnosed with second malignancies (2 children with AT and 2 children with NBS. The diagnosis of PID was suspected or confirmed before the initiation of cancer therapy in 62% of AT patients and in 100% of NBS patients. Treatment was given in accordance with standard protocols with chemotherapy dose modifications. A total of 93% of patients with AT and 80% of patients with NBS required dose reduction. The level of response was quite high: 81% of patients with AT and 58% of patients with NBS achieved complete remission. According to our data, the use of reduced-dose chemotherapy regimens helps to achieve an acceptable toxicity profile without reducing the overall effectiveness of treatment.

Lympho- and Myeloproliferative Malignancies Occurring in the Same Host: Description of a Nationwide Discovery Cohort

Background: So far, myeloid and lymphoid malignancies have been considered as diseases with distinct pathogenetic mechanisms. However, recent studies (Frederiksen H et al, Blood 2011) have reported an increased risk of lymphoid malignancies in patients with chronic myeloproliferative neoplasms (MPN). Moreover, genomic studies in patients with angioimmunoblastic T-cell lymphoma (AITL) have revealed mutations in epigenetic modifier genes, such as IDH-2, TET2, and DNMT3A4, which are usually not seen in lymphomas, while they are commonly found in patients with myeloid diseases.Aim: The aim of our work was to identify and validate a nationwide cohort of patients, who were diagnosed with MPN as well as a lymphoid malignancy either simultaneously or sequentially. The establishment of this cohort is currently serving as a discovery platform for possible shared pathogenetic pathways in myeloid and lymphoid disease entities.Methods: Patients diagnosed with both MPN and a lymphoid malignancy within the period 1990-2015 were identified through the National Danish Pathology Registry. In order to minimize the occurrence of therapy related secondary myelodysplasias, only patients diagnosed either with both diseases simultaneously (i.e. within maximum half a year from each other) or with MPN first and later with a lymphoid malignancy were selected for further histopathological revision. Formalin-fixed paraffin-embedded tissue specimens from 16 different pathology departments throughout Denmark were collected. All specimens were reviewed by an experienced hematopathologist (TLP) at a tertiary referral center.Results: The algorithm leading to the establishment of the study cohort is shown in Figure 1. Ninety-seven patients fulfilled the described inclusion criteria. Demographically, 48.5% of the patients were females. The age at diagnosis ranged between 18.5-93.7 years and the median age at MPN diagnosis was 70.8 years (interquartile range 62.8-79.9 years). The average time between the diagnosis of MPN and that of lymphoid malignancy was 1.5 years and in the majority of the patients (90%) both diagnoses were established within 5 years from each other. The myeloid and lymphoid diagnoses for each individual patient are shown in Table 1. If one looks at mature, non-primary leukemic non-Hodgkin lymphomas, i.e. excluding lymphoblastic lymphoma, chronic lymphocytic leukemia, Waldenström macroglobulinemia, and Hodgkin lymphoma, an excess of peripheral T-cell lymphomas (PTCL) was observed (17%), at a frequency almost double as high as the one expected in a Caucasian population-based non-Hodgkin lymphoma cohort (8-10%). Interestingly, most PTCL diagnoses were of AITL type.Conclusion: The establishment of this unique series of tissue specimens from patients with co-existing myelo- and lymphoid malignancies revealed, among primary systemic non-Hodgkin lymphomas, an excess of PTCL in general and AITL in particular. Genomic studies are ongoing to search for shared pathogenetic steps explaining the co-occurrence of MPN and lymphoid malignancies in the same host. [Display omitted] Disclosuresd'Amore:Nordic Nanovector: Other: Advisory Board; Les Laboratoires Servier: Honoraria, Other: Advisory Board; Takeda Pharma: Honoraria, Other: Advisory Board, Research Funding; Sanofi: Research Funding.

Metformin and the Incidence of Lymphoid Malignancies in Patients with Type 2 Diabetes

Purpose: Metformin, a first-line antidiabetic drug in type 2 diabetes, is being evaluated for prevention and treatment of various solid tumors. Metformin has also been shown to act against lymphoid malignancies (LM) in preclinical models, although population-based data are lacking. Thus, we examined whether metformin use is associated with reduced risk of LM in patients with type 2 diabetes.Patients and Methods: This was a population-based cohort study using data from the United Kingdom Clinical Practice Research Datalink. We included patients > 18 years of age newly-treated with non-insulin antidiabetic drugs between 1998 and 2014. Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) of LM (inpatient diagnoses of non-Hodgkin and Hodgkin lymphoma, chronic and acute lymphocytic leukemia, and multiple myeloma) comparing the use of metformin with the use of other antidiabetic drugs, and lagged by one year for cancer latency. Secondary analyses included stratifications of metformin use by cumulative duration and dose, as well as of LM by disease type. All estimates were adjusted to ethnicity, socioeconomic status, time-updated use of other antidiabetic drugs, known risk factors (autoimmune diseases and solid organ transplant), and important comorbidities.Results: The cohort included a total of 100,091 patients, which generated 502 LM events during 500,774 person-years of follow-up (rate, 1/1000 person-years). Overall, metformin use was not associated with the incidence of LM (adjusted HR, 0.86; 95% CI, 0.63-1.16). Furthermore, there was no significant trend for duration (P=0.46) or cumulative dose (P= 0.60) of metformin use with LM incidence, with the highest categories being > 5 years and > 2,492 grams (Table 1). When stratified by disease type, metformin use was not associated with the incidence of multiple myeloma, chronic lymphocytic leukemia acute, and non-Hodgkin lymphoma (Table 2). Similar findings were seen for acute lymphoblastic leukemia (adjusted HR, 0.36; 95% CI, 0.04-3.41), and Hodgkin lymphoma (adjusted HR, 0.94; 95% CI, 0.23-3.91).Conclusions To our knowledge, this is the first population-based study to examine the association between metformin use and LM incidence. We observed no duration- or dose-response of metformin with LM incidence, which are paramount in the concept of chemoprevention. There were no important differences between LM types, although precision for acute lymphoblastic leukemia and Hodgkin lymphoma was limited due to sample size. While our findings are observational and apply to the diabetic population, our findings provide no rationale for the prospective investigation of metformin to prevent LM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Risks of Solid and Lymphoid Malignancies in Patients with Myeloproliferative Neoplasms: Clinical Implications.

Simple SummaryPatients with chronic myeloproliferative neoplasms (MPNs) such as polycythemia vera and essential thrombocythemia have an elevated risk of acute leukemia. Recently, it has been recognized that the risk of solid cancers is also increased. In the past decade, several studies have compared cancer frequency in patients with MPNs with the general population. In our study, we present results sampled from 12 previous studies, totaling more than 65,000 patients with MPNs identified through large registries. Patients with MPNs were compared to the age/sex-matched general population. Our results show that risk of new cancers is 1.5–3.0-fold elevated in patients with MPNs. In particular, lymphomas and cancers of the skin, lung, kidney, and thyroid gland occur more frequently. The difference in cancer occurrence is highest in the age group 60–79 years. Our results indicate that clinical follow up of patients with MPNs should include awareness of the increased cancer risk.In the past decade, several studies have reported that patients with chronic myeloproliferative neoplasms (MPNs) have an increased risk of second solid cancer or lymphoid hematological cancer. In this qualitative review study, we present results from studies that report on these cancer risks in comparison to cancer incidences in the general population or a control group. Our literature search identified 12 such studies published in the period 2009–2018 including analysis of more than 65,000 patients. The results showed that risk of solid cancer is 1.5- to 3.0-fold elevated and the risk of lymphoid hematological cancer is 2.5- to 3.5-fold elevated in patients with MPNs compared to the general population. These elevated risks apply to all MPN subtypes. For solid cancers, particularly risks of skin cancer, lung cancer, thyroid cancer, and kidney cancer are elevated. The largest difference in cancer risk between patients with MPN and the general population is seen in patients below 80 years. Cancer prognosis is negatively affected due to cardiovascular events, thrombosis, and infections by a concurrent MPN diagnosis mainly among patients with localized cancer. Our review emphasizes that clinicians caring for patients with MPNs should be aware of the very well-documented increased risk of second non-myeloid cancers.

Second Myeloid and Lymphoid Malignancies in patients with Chronic Lymphocytic Leukemia

in relapsed/refractory (R/R) CLL. Ofatumumab, an anti-CD20 antibody, has activity in combination with chemotherapy in CLL. Objective: Evaluate safety and activity of ibrutinib combined with ofatumumab (phase Ib/II) in 3 different sequences. Patients: Patients with R/R CLL/SLL, PLL, or Richter’s transformation (RT) after 2 prior therapies, including a purine analogue. Intervention: 420 mg oral ibrutinib daily and IV ofatumumab 300/2000 mg (12 doses). Group (G) 1: 1 cycle of ibrutinib, then ofatumumab added; G2: ofatumumab on day (D) 1/cycle (C) 1 and ibrutinib on D2/C1; G3: 2 cycles of ofatumumab, then ibrutinib added on D1/ C3. Results: 71 patients (27, 20, 24 in G1, G2, G3) enrolled; median age 64 years; Rai stage III/IV 61%; 65 had CLL, 1 SLL, 2 PLL, and 3 RT; bulky disease ( 5 cm) in 75%; del(17p) in 44%; del(11q) in 31%. Most frequent AEs included diarrhea (68%), infusion-related reaction (IRR, 45%), peripheral sensory neuropathy (42%), and stomatitis (37%). AEs grade 3 occurred in 61%; most common grade 3-4 AE was neutropenia (17%). Serious AEs occurred in 39%, including grade 3 IRR in 1 patient (G2). AEs led to ibrutinib discontinuation in 6 patients. Nine patients died within 30 days of last dose and 2 within follow-up. ORR in CLL/SLL was 100% in G1, 79% in G2, and 71% in G3. One patient had complete response; 2 additional patients achieved partial response with lymphocytosis. Four patients in G3 progressed before starting ibrutinib. At study end, 52/58 responders (90%) remained progression-free with follow-up of 16, 12, and 11 months for G1, G2, and G3, respectively. The three RT patients had disease control followed by progression on days 471, 168, and 137. At 12 months, PFS was 89%, 85%, and 75% in G1, G2, and G3, respectively; 76% continued ibrutinib in long-term extension study; 2 patients underwent transplant. Conclusions: Ibrutinib combined with ofatumumab is well tolerated and highly active in R/R CLL/SLL with all 3 dosing sequences. Based on these compelling results, randomized trials evaluating anti-CD20 antibody in combination with ibrutinib are ongoing. 310 Second Myeloid and Lymphoid Malignancies in patients with Chronic Lymphocytic Leukemia Jose Sandoval, Gabriela Corrales, Jennifer Rock-Klotz, Javier Pinilla-Ibarz, Julio Chavez Malignant Hematology, H. Lee Moffitt Cancer Center, University of South Florida; Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute Introduction: Chronic lymphocytic Leukemia (CLL) as the most common chronic leukemia is associated with increased second malignancies. We describe the characteristics of CLL patients who develop second myeloid (SMD) or lymphoid disorders (SLD). Methods: This is a retrospective review of CLL patients with of SLD and SMD from 01/2000 to 12/2012 using the Moffitt Cancer Canter and Total Cancer Care databases. The primary objective was to identify risk factors for SLD and SMD development. CLL patients with no malignancies were the control. Overall survival (OS) was estimated and compared by the Kaplan-Meier method and the long-rank test. Results: We identified 211 CLL patients with second malignancies in a cohort of 844. Sixty-nine patients had SLD (47) and SMD (22). SLD diagnosis included: DLBCL1⁄4 40, MM1⁄44, PLL1⁄4 1, HCL1⁄41, CTCL1⁄41. SMD diagnosis included MDS1⁄4 15, AML/MDS1⁄47. The OS for patients with SLD, SMD and control were 11.4, 8.1 (p1⁄4 0.063) and 10.7 years (p1⁄4 0.261), respectively. The median OS from SLD and SMD diagnosis were 1.2 and 1.3 years, respectively. Table 1 shows Chi-square analysis. Conclusions: Advanced Rai stage and unmutated IgVH status were associated with increased risk of SLD while no factors were found for SMD. Secondary hematological malignancies in CLL patients show a short median OS. Clinical Lymphoma, Myeloma & Leukemia June 2015 S207 Table 1 Chi-Square Analysis No second malignancies SLD p-Value SMD p-Value Gender M 400 (63%) 33 (70%) 0.43 15 (68%) 0.82 F 233 (37%) 14 (30%) 7 (32%) Age >60 304 (48%) 24 (51%) 0.76 13 (59%) 0.66 <60 329 (52%) 23 (49%) 9 (41%) Clinical and laboratory

Case control study to identify the risk factors for development of lymphoma in patients with hepatitis C infection.

e19519 Background: Multiple studies have demonstrated an increased risk of lymphoid malignancies in patients with hepatitis C infection. It is clear that not all patients with hepatitis C infection...

Reply to Dr. M. Weyl Ben Arush

Medical and Pediatric OncologyVolume 32, Issue 6 p. 480-480 Letter to the EditorFull Access Reply to Dr. M. Weyl Ben Arush Claudio Sandoval MD, Claudio Sandoval MD Department of Pediatrics and Institute for the Genetic Analysis of Common Diseases, New York Medical College, Valhalla, New YorkSearch for more papers by this authorMichael Swift MD, Michael Swift MD Department of Pediatrics and Institute for the Genetic Analysis of Common Diseases, New York Medical College, Valhalla, New YorkSearch for more papers by this author Claudio Sandoval MD, Claudio Sandoval MD Department of Pediatrics and Institute for the Genetic Analysis of Common Diseases, New York Medical College, Valhalla, New YorkSearch for more papers by this authorMichael Swift MD, Michael Swift MD Department of Pediatrics and Institute for the Genetic Analysis of Common Diseases, New York Medical College, Valhalla, New YorkSearch for more papers by this author First published: 05 May 1999 https://doi.org/10.1002/(SICI)1096-911X(199906)32:6<480::AID-MPO26>3.0.CO;2-KAboutReferencesRelatedInformationPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessClose modalShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. REFERENCES 1Abadir R, Hakamin N. Ataxia-telangiectasia with cancer: an indication for reduced radiotherapy and chemotherapy doses. Br J Radiol 1983; 56: 343– 344. Medline 2Weyl Ben Arush M, Rosenthal J, Dale J, et al. Ataxia-telangiectasia and lymphoma: an indication for individualized chemotherapy dosing—report of treatment in a highly inbred Arab family. Pediatr Hematol Oncol 1995; 12: 163– 169. Medline 3Sandoval C, Swift M. Treatment of lymphoid malignancies in patients with ataxia-telangiectasia. Med Pediatr Oncol 1998; 31: 491– 497. Medline 4Taylor AMR, Rosney CM, Campbell JB. Unusual sensitivity of ataxia-telangiectasia cells to bleomycin. Cancer Res 1979; 9: 1046– 1050. Volume32, Issue6June 1999Pages 480-480 ReferencesRelatedInformation RecommendedWeyl Groups are Finite — and Other Finiteness Properties of Cartan SubalgebrasKarl H. Hofmann, Jimmie D. Lawson, Wolfgang A. F. Ruppert, Mathematische NachrichtenQuantum Weyl Reciprocity for CohomologyBrian J. Parshall, Leonard L. Scott, Proceedings of the London Mathematical SocietyWeyl's Theorem, a-Weyl's Theorem, and Local Spectral TheoryRaúl E. Curto, Young Min Han, Journal of the London Mathematical SocietySchur–Weyl duality for orthogonal groupsStephen Doty, Jun Hu, Proceedings of the London Mathematical SocietyA constructive proof of the Peter‐Weyl theoremThierry Coquand, Bas Spitters, Mathematical Logic Quarterly

Treatment of lymphoid malignancies in patients with ataxia‐telangiectasia

Background. Patients with ataxia-telangiectasia (A-T) are at an increased risk for developing lymphoid malignancies, yet the appropriate therapy remains unknown. Radiation therapy at conventional doses results in destruction of normal tissue, which has suggested that full-dose chemotherapy might result in unacceptable toxicity in A-T patients with cancer. Procedure. The medical records of 412 A-T patients were reviewed to identify those patients who developed lymphoid malignancies and to analyze the type and duration of therapy, events during therapy, and off-therapy follow-up. Results. Of 74 A-T patients with lymphoid | malignancies, 32 patients received chemotherapy. The 21 patients treated with standard chemotherapy had a significantly better median survival (9 months, range, 1-162+ months vs. 5 months, range, 0.5-28 months) (P = 0.03) and complete remission rate (76% vs. 9%) (P = 0.001) than the 11 treated with reduced dose chemotherapy. Three of the 21 full-dose chemotherapy patients required dose reductions because of neutropenia. Seven of the 14 patients exposed to 1,200 mg/m 2 or greater of cyclophosphamide developed hemorrhagic cystitis. All three patients exposed to bleomycin developed pulmonary disease which was fatal in two. Of the 16 standard-dose chemotherapy patients who achieved a complete remission, two remain disease-free, five have died of recurrent disease, and five died of pulmonary disorders and four of other causes while in remission. Conclusions. Standard-dose chemotherapy should be given to each A-T patient with a lymphoid malignancy unless additional physical or emotional problems make it unlikely that the patient will benefit. Morbidity and mortality may be reduced by prophylaxis against hemorrhagic cystitis and early detection and treatment of pulmonary disorders.

Treatment of lymphoid malignancies in patients with ataxia-telangiectasia.

Patients with ataxia-telangiectasia (A-T) are at an increased risk for developing lymphoid malignancies, yet the appropriate therapy remains unknown. Radiation therapy at conventional doses results in destruction of normal tissue, which has suggested that full-dose chemotherapy might result in unacceptable toxicity in A-T patients with cancer. The medical records of 412 A-T patients were reviewed to identify those patients who developed lymphoid malignancies and to analyze the type and duration of therapy, events during therapy, and off-therapy follow-up. Of 74 A-T patients with lymphoid malignancies, 32 patients received chemotherapy. The 21 patients treated with standard chemotherapy had a significantly better median survival (9 months, range, 1-162+ months vs. 5 months, range, 0.5-28 months) (P = 0.03) and complete remission rate (76% vs. 9%) (P = 0.001) than the 11 treated with reduced dose chemotherapy. Three of the 21 full-dose chemotherapy patients required dose reductions because of neutropenia. Seven of the 14 patients exposed to 1,200 mg/m2 or greater of cyclophosphamide developed hemorrhagic cystitis. All three patients exposed to bleomycin developed pulmonary disease which was fatal in two. Of the 16 standard-dose chemotherapy patients who achieved a complete remission, two remain disease-free, five have died of recurrent disease, and five died of pulmonary disorders and four of other causes while in remission. Standard-dose chemotherapy should be given to each A-T patient with a lymphoid malignancy unless additional physical or emotional problems make it unlikely that the patient will benefit. Morbidity and mortality may be reduced by prophylaxis against hemorrhagic cystitis and early detection and treatment of pulmonary disorders.