scholarly journals Very High Seroprevalence of CMV and EBV Among a Large Series of Patients with Hematological Malignancies at a Tertiary Care Center in Saudi Arabia - a Case for Investigating Cooperativity of Viruses in Carcinogenesis?

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5818-5818
Author(s):  
Abdul Rehman Z. Zaidi ◽  
Maged O. Al-Ammari ◽  
Mohammed AlNoamani ◽  
Syed Y. Altaf ◽  
Nawal AlShehry ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Hodgkin’S Lymphoma ◽  
Hematological Malignancies ◽  
Hodgkin's Lymphoma ◽  
Cell Transplant ◽  
High Seroprevalence ◽  
Lymphoid Malignancies ◽  
Igm Antibodies ◽  
Significant Difference ◽  
Very High

Background: Hematology practice in developing countries has some unique issues including a higher prevalence of infectious disease markers. Epstein-Barr virus (EBV) is an oncogenic virus and implicated in Burkitt's lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma and leiomyosarcoma in the immunocompromised (Ito Y et al. 2009). Cytomegalovirus (CMV) infection/reactivation in patients with hematological malignancies causes serious morbidity and mortality. Saudi Arabia is a high income rapidly developing country, but seroprevalence of CMV and EBV is reportedly higher compared to developed countries (Ghazi 2002, Seale et al., 2006, Joseph et al., 2005). EBV & CMV co-infection is not infrequent & occurs most commonly in the immunocompromised host. A significantly higher prevalence of antibodies (Abs) against CMV & EBV in some disease groups compared to controls has been reported from the same communities (Ocak et al., 2006, Al-Hakami et al., 2016). Interestingly, CMV disease occurrence in sibling donor hematopoietic stem cell transplant (HSCT) is infrequent in our area in spite of the occurrence of CMV reactivations (Aljurf et al., 2009, Saovic et al., 1999). Hence, knowledge of seroprevalence of these viruses in hematological malignancies may be helpful in strategic planning for transplants & transfusions. It may help in establishing any plausible etiological linkage with certain hematological malignancies. Methods: We retrospectively examined the records of adult patients (>14 years) with hematological malignancies for CMV and EBV status (IgG and IgM Abs by chemiluminescence immunoassay). We identified 2,007 patients (1104 males and 903 females) and grouped them according to gender along with broad hematological malignancy categories (Table 1). We tried to establish if any disease category had extraordinary seropositivity for CMV (IgG ≥20 U/ml) or EBV (IgG ≥12 U/ml). We also studied the prevalence of IgM Abs in those tested positive for IgG Abs. Results: Of 2,007 patients (males significantly more than females, p = 0.001), age range 14-93 year (mean 47.2), 503 underwent testing for CMV status and 520 for EBV. Among these tested patients, there was no significant gender difference as 96.1% males were CMV positive, and 95.4% females were CMV positive. On the other hand, 96.9% males were EBV IgG Abs positive compared to 92.5% of females, which was 2.56 (95% CI; 1.12 - 5.96) times more likely to be positive in the studied male patient population (p = 0.021). Overall seroprevalence for CMV IgG Abs was 95.4%, and for EBV IgG Abs it was 95% (Table 1). Among those with CMV IgG Abs, 25/482 (5.1%) had very high antibodies titer (>180 U/ml), and 23/25 patients (92%) had lymphoid malignancies (11 NHL, 7 HL, 2 ALL, 3 MM) and 2 had CML. Among those with EBV IgG Abs 59/495 (11.9%) had very high antibodies titer (>750U/ml); and 46/59 (77.97%) of these patients had lymphoid malignancies (20 HL, 16 NHL, 6 ALL, 4 CLL, 1 MM) and 13/59 (22.03%) had myeloid neoplasms (6 AML, 5 CML, 1 MDS, 1 MPN). Six patients had very high titers for both EBV and CMV antibodies. In CMV IgG Abs positive patients only 1.03% (5/482) had IgM antibodies, and in EBV IgG Abs positive only 2.22% (11/495) had IgM antibodies. Table 1 shows the prevalence across the gender and in different disease categories. The highest seroprevalence for CMV was found in CLL, multiple myeloma and MDS patients (100%); and for EBV it was highest in MDS and MPN patients (100%). Relatively lower seroprevalence of EBV was noted in ALL patients group (86.2%), and lower seroprevalence of CMV was noted in MPN patients group (87.5%). However, overall, there was no significant difference across the disease categories for either CMV (p = 0.362) or EBV (p = 0.114). Conclusions: In this large study on our patients with hematological malignancies, we report very high seroprevalence of CMV and EBV Abs, reaching up to 100% in some disease categories. Among those with very high titer of EBV IgG Abs, the majority had lymphoid malignancies. Short of establishing any etiological linkage, we noticed 100% of MDS patients had both CMV and EBV Abs. Contrary to other reports, our male patients were more likely to be EBV positive compared to the females. Our results support the need for further studies to investigate possible cooperative linkage of EBV and CMV in carcinogenesis. Disclosures No relevant conflicts of interest to declare.

Non-Hodgkin's Lymphoma in the Elderly: A Retrospective Evaluation of Toxicity Related to Aggressive vs. Conservative Treatments

1988 ◽  
Vol 74 (4) ◽  
pp. 433-438 ◽  
Author(s):  
Umberto Tirelli ◽  
Vittorina Zagonel ◽  
Rachele Volpe ◽  
Mauro G. Trovo ◽  
Antonino Carbone
Keyword(s):  
Elderly Patients ◽  
Hodgkin’S Lymphoma ◽  
Randomized Trials ◽  
Survival Rates ◽  
The Elderly ◽  
Hodgkin's Lymphoma ◽  
Severe Toxicity ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Significant Difference

The outcome of 70 elderly patients aged 65 years or more (median, 71 years) with non-Hodgkin's lymphoma (NHL) treated between 1973 and 1981 with aggressive (AM) or conservative modalities (CM) was retrospectively evaluated. A significantly higher incidence of lethal and severe toxicity was observed in patients treated with AM than in those treated with CM (32 % vs 3 %, p < 0.01), with 10 % treatment related deaths in the AM group. Only 56 % of the deaths were attributed to NHL; other major causes were treatment-related deaths, infection and cardiac diseases. No significant difference in response and survival was found between AM and CM groups (complete remission rates were 35 % vs 42 %, and 10 year survival rates were 31 % vs 19 %, respectively), but the prevalence of stages III-IV in patients treated with AM makes these results meaningless. Prospective randomized trials with AM vs CM are clearly needed in elderly patients with advanced unfavorable NHL.

scholarly journals Impact of radiation techniques on lung toxicity in patients with mediastinal Hodgkin’s lymphoma

2020 ◽  
Author(s):  
Niklas Benedikt Pepper ◽  
Michael Oertel ◽  
Christopher Kittel ◽  
Kai Jannes Kröger ◽  
Khaled Elsayad ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Hodgkin’S Lymphoma ◽  
Radiation Pneumonitis ◽  
Organs At Risk ◽  
Normal Tissue Complication Probability ◽  
Lung Toxicity ◽  
Hodgkin's Lymphoma ◽  
Significant Difference ◽  
Radiation Induced ◽  
Increase In Risk

Abstract Purpose Mediastinal radiotherapy (RT), especially when combined with bleomycin, may result in substantial pulmonary morbidity and mortality. The use of modern RT techniques like intensity-modulated radiotherapy (IMRT) is gaining interest to spare organs at risk. Methods We evaluated 27 patients who underwent RT for Hodgkin’s lymphoma between 2009 and 2013 at our institution. For each patient, three different treatment plans for a 30-Gy involved-field RT (IFRT) were created (anterior-posterior-posterior-anterior setup [APPA], 5‑field IMRT, and 7‑field IMRT) and analyzed concerning their inherent “normal tissue complication probability” (NTCP) for pneumonitis and secondary pulmonary malignancy. Results The comparison of different radiation techniques showed a significant difference in favor of standard APPA (p < 0.01). The risk of lung toxicity was significantly higher in plans using 7‑field IMRT than in plans using 5‑field IMRT. The absolute juxtaposition showed an increase in risk for radiation pneumonitis of 1% for plans using 5‑field IMRT over APPA according to QUANTEC (Quantitative Analyses of Normal Tissue Effects in the Clinic) parameters (Burman: 0.15%) and 2.6% when using 7‑field IMRT over APPA (Burman: 0.7%) as well as 1.6% when using 7‑field IMRT over 5‑field IMRT (Burman: 0.6%). Further analysis showed an increase in risk for secondary pulmonary malignancies to be statistically significant (p < 0.01); mean induction probability for pulmonary malignoma was 0.1% higher in plans using 5‑field IMRT than APPA and 0.19% higher in plans using 7‑field IMRT than APPA as well as 0.09% higher in plans using 7‑field IMRT than 5‑field IMRT. During a median follow-up period of 65 months (95% confidence interval: 53.8–76.2 months), only one patient developed radiation-induced pneumonitis. No secondary pulmonary malignancies have been detected to date. Conclusion Radiation-induced lung toxicity is rare after treatment for Hodgkin lymphoma but may be influenced significantly by the RT technique used. In this study, APPA RT plans demonstrated a decrease in potential radiation pneumonitis and pulmonary malignancies. Biological planning using NTCP may have the potential to define personalized RT strategies

Cytodiagnostic Sensitivity of Fine Needle Aspiration Biopsy for Hodgkin’s Lymphoma Is Decreased in Patients with Human Immunodeficiency Virus Infection

2019 ◽  
Vol 63 (5) ◽  
pp. 352-360 ◽  
Author(s):  
Adam J. Perricone ◽  
Mohammad K. Mohammad ◽  
Rachel L. Geller ◽  
Marina B. Mosunjac
Keyword(s):  
Fine Needle Aspiration ◽  
Hodgkin’S Lymphoma ◽  
Needle Aspiration ◽  
Diagnostic Sensitivity ◽  
Hodgkin's Lymphoma ◽  
P Value ◽  
Hiv Patients ◽  
Female Ratio ◽  
Fine Needle ◽  
Significant Difference

Objective: We aimed to evaluate the sensitivity of fine needle aspiration (FNA) for the diagnosis of Hodgkin’s lymphoma (HL) in HIV-infected patients. Study Design: An electronic search was conducted to retrospectively identify patients diagnosed with HL who underwent FNA followed by confirmatory biopsy. FNAs were categorized as negative, atypical/suspicious/positive, or nondiagnostic. Diagnostic sensitivity in HIV+ and HIV– patients was statistically compared via Fisher’s exact test, with a p value <0.05 considered significant. Results: Thirty-six patients meeting inclusion criteria were identified (24 HIV– and 12 HIV+). Average age was 36.0 ± 11.5 and 36.5 ± 7.4 years (means ± SD) in HIV– and HIV+ patients, respectively. The male-to-female ratio was 1.4:1 in HIV– patients versus 3:1 in HIV+ patients. Among these 36 patients, a total of 42 FNAs were performed. Overall sensitivity of FNA was 66.7% (95% confidence interval: 52.4–80.9%). When stratified by HIV status, a statistically significant difference in FNA sensitivity was detected, as sen­sitivity was 84.6% (70.8–98.4%) in HIV– patients versus only 37.5% (13.8–61.2%) in HIV+ patients (p =0.003). Conclusion: The diagnostic sensitivity of FNA biopsy was significantly attenuated in the HIV+ cohort. In HIV-infected patients presenting with lymphadenopathy, increased clinical suspicion of HL is critical to avoid misdiagnosis.

Expression of the Chk2 Gene Is Downregulated in Hodgkin’s Lymphoma Cell Lines Via Epigenetic Mechanisms.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 429-429
Author(s):  
Naoko Kato ◽  
Takeshi Kondo ◽  
Junichi Tsukada ◽  
Yoshiya Tanaka ◽  
Yasuhiro Minami ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Dna Damage Response ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Epigenetic Mechanisms ◽  
Apoptosis Resistance ◽  
Down Regulation ◽  
Lymphoid Malignancies ◽  
Damage Response

Abstract Chk2, the mammalian homologue of the yeast Rad53 and Cds1 genes, encodes a nuclear serine/threonine kinase that plays a crucial role in the DNA damage response and helps guard the integrity of the genome by regulating cell-cycle checkpoints, DNA repair and apoptosis. Furthermore Chk2 is regarded as a tumor suppressor gene. Alterations in tumor suppressors that are involved in the DNA damage response have been reported to be frequently involved in the pathogenesis of lymphoid malignancies. We investigated the expression levels of the genes encoding Chk2 in nine cell lines from lymphoid malignancies, including three Hodgkin’s lymphoma (HL) cell lines. We found that all three HL cell lines exhibited a drastic reduction in Chk2 mRNA and protein expression compared to the other cell lines without any apparent mutation of the Chk2 gene. Accumulating evidence demonstrates the importance of posttranslational modification of histone proteins in addition to DNA methylation, as epigenetic mechanisms involved in the organization of chromosomal domains and gene regulation. It is now generally appreciated that hyperacetylated histones H3 and H4 are associated with activated genomic regions, while hypoacetylation of histones H3, H4 and methylation on H3-lysine 9 results in gene repression and silencing. Therefore we tested the possibility that epigenetic mechanisms are involved in this aberrant expression of the Chk2 gene in these cells using the histone deacetylase (HDAC) inhibitors trichostatin A (TsA) and sodium butyrate (SB). Expression of Chk2 in HL cells was restored following treatment with the TsA and SB, or 5Aza-dC. Chromatin-immunoprecipitation (Chip) assays revealed that treatment of HL cells with TsA, SB or 5Aza-dC resulted in increased levels of acetylated histones H3 and H4, and decreased levels of dimethylated H3 lysine 9 at the Chk2 promoter. These results indicate that expression of the Chk2 gene is down-regulated in HL cells via epigenetic mechanisms. Furthermore we examined whether the down regulation of Chk2 gene in HL cells may be involved in apoptosis resistance to irradiation (IR). We found that upregulation of Chk2 in HL cells following treatment by SB resulted in increased susceptibility of the cells to IR. Therefore, our findings suggested that altered epigenetic regulation of Chk2 gene in HL cells results in the down-regulation of Chk2 kinase and abrogates DNA damage response signaling in the cells

Patterns and Timing of Initial Relapse in Patients with Hodgkin’s and Non-Hodgkin’s Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3673-3673 ◽  
Author(s):  
Sughosh Dhakal ◽  
Tithi Biswas ◽  
Sheema Chawla ◽  
Nikhil Uppal ◽  
Christopher Beck ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Treatment Strategies ◽  
Autologous Stem Cell Transplant ◽  
Hodgkin's Lymphoma ◽  
Cell Transplant ◽  
Local Recurrences ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Aggressive Histology

Abstract Purpose/Objective: To evaluate patterns of recurrence in patients with Hodgkin’s (HL) and non-Hodgkin’s lymphoma (NHL) who subsequently undergo autologous stem cell transplant (ASCT). In this population that has declared itself as high risk, we evaluated time to and sites of relapse relative to initial sites of disease and radiation therapy (RT). This information might enhance understanding of the natural history of these diseases in the setting of modern therapy, influence treatment strategies, and assist in screening decisions. Materials/Method: We analyzed the records of all 281 consecutive patients with refractory or recurrent HL and NHL (indolent and aggressive, as defined at initial diagnosis) who underwent ASCT in our center between 5/92–7/03. Patients were initially diagnosed between 1979–2003 at a median age of 44 years (8–70). 25 patients were unevaluable due to insufficient data, and 68 patients were excluded from analysis because their disease was refractory to initial and salvage therapy. HL patients were segregated according to initial staging (I/II vs. III/IV). Results: Early stage HL patients relapsed at a median of 2.0 years (0.5–10.3) with 87% relapsing in initial disease site(s); 13% (95% CI 3.8–30.1%) relapsed only in new sites. Advanced stage HL patients relapsed at a median of 1.4 years (0.6–10.5) with 96% relapsing in initial site(s); 4% (95% CI 0.1–21.9%) relapsed only in new sites. Indolent histology NHL patients relapsed at a median of 2.1 years (0.5–14.9) with 83% relapsing in initial site(s); 17% (95% CI 7.3–32.8%) relapsed only in new sites. Aggressive histology NHL patients relapsed at a median of 1.0 year (0.3–8.0) with 64% relapsing in initial site(s); 36% (95% CI 26.2–46.2%) relapsed only in new sites. For early stage HD patients, recurrences were predominantly local, and uniformly so in those unirradiated. For all other groups, fewer patients were irradiated than unirradiated and local recurrences predominated regardless of therapy. Conclusions: Almost all patients with HL who relapse and subsequently undergo ASCT initially recur in previous disease sites. Although patients with aggressive histology NHL are more likely to relapse in new sites than patients with indolent NHL, local recurrences predominate in both groups. The median time to recurrence is brief (1–2.1 years). In a population defined by recurrent disease, it is expected that relapses will occur in irradiated sites. Relative protection by RT of local recurrence cannot be determined until all patients, regardless of relapse status, are analyzed. However, these data support an emphasis on local control and suggest that the frequency of screening be most rapid in the early post-therapy years. Comparison of Site(s) of Relapse to Site(s) of Initial Presentation HL NHL Early (n=30) Adv. (n=23) Ind. (n=40) Agg. (n=95) Characteristic % % % % New Site(s) 13 4 18 36 Previous site(s) only 63 61 60 44 Previous site(s) + new site(s) 23 35 23 20 Characteristic n n n n Radiated patients relapsing in previous site(s) 15/19 6/6 5/7 20/34 Unradiated patients relapsing in previous site(s) 11/11 16/17 26/33 42/61

Combined VBM Chemotherapy and Involved Field (IF) Radiotherapy in Early Stage Hodgkin’s Lymphoma (HL): A Single Centre Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4463-4463
Author(s):  
Emilia Cocorocchio ◽  
Fedro A. Peccatori ◽  
Federica Gigli ◽  
Simona Bassi ◽  
Luca Nassi ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Alkylating Agents ◽  
Performance Status ◽  
Low Risk ◽  
Hodgkin's Lymphoma ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Before And After

Abstract Early stage HL patients (pts) benefit from a short course of chemotherapy combined with IF radiotherapy. In our previous experience six courses of VBM chemotherapy (Stanford regimen) were administered with IF radiotherapy. However, despite good clinical results, the schedule was modified in terms of total chemotherapy cycles delivered, in order to reduce the risk of long term toxicities. PET and CT scan were performed at staging to identify a low risk patients (pts) group. From May 2001 to November 2006, 32 treatment naïve Hodgkin’s lymphoma pts (18 male, 14 female) were treated with four courses of VBM chemotherapy (D1, 8: Vinblastine 6 mg/sm, Bleomycin 10 mg/sm, Methotrexate 30 mg/sm, repeated every 28 days) followed by IF radiotherapy. Median age was 37 years (range 16–73). Main histology was classical HL in 26 pts, while lymphocyte predominant was observed in 6 pts. Pts were all stage I-IIA (no bulky disease), no more than three sites involved, performance status 0–1 and ESR < 50. CT scans were performed before and after chemotherapy and radiotherapy. PET scans were performed before and after chemotherapy in 26 pts, and after radiotherapy if not performed before or in case of positivity after chemotherapy. Chemotherapy was usually well tolerated: three pts experienced G3-4 neutropenia while the main non- haematological toxicities recorded were G3 transaminitis in 3 pts and G1-2 neuroconstipation/abdominal pain in 18 pts. IF radiotherapy was performed one month after the last chemotherapy cycle; median dose administered was 30Gy (range 26–30.4). At the end of chemotherapy 7 pts were PET positive. While one patient developed progressive disease, the other six pts became negative after radiotherapy and are still in complete remission (CR). 29 pts (90%) completed the whole program obtaining a CR. Two pts progressed before radiotherapy, while one patient shifted to an anthracycline containing schedule after two cycles due to stable disease. With a median follow-up of 42 months (range: 7–73), all pts are alive. 1 out of 29 CR pts progressed and is now receiving intensive chemotherapy program with autologous stem cell transplant. In our experience four cycles of VBM chemotherapy combined with IF radiotherapy is an effective program. Furthermore this regimen that doesn’t contain alkylating agents or anthracyclines avoids alopecia and decreases the risk of long term toxicity. PET scan effectively helps to identify low risk early stage HL pts that can take advantage of this therapeutic approach.

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