Requirement for containing etoposide in the initial treatment of lymphoma associated hemophagocytic lymphohistiocytosis

Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory status caused by a hereditary or acquired immunoregulatory abnormality. It is divided into two categories: primary and secondary. Secondary HLH (sHLH) is often associated with and caused by infections, malignant tumors, and autoimmune diseases. Lymphoma associated HLH (LAHS) is one of the most common sHLH, usually presents worse prognosis higher mortality. The treatment strategy for LAHS is still controversial. Etoposide is one of the key drug in HLH-94/04 regimen. We sought to identify the importance of including etoposide in the initial treatment of LAHS, especially comparing with the high dose chemotherapy. Methods: The patients diagnosed as LAHS in our center between Jan 1 2015 and Dec 31 2017 were observed. Survival times were calculated from the date of diagnosis of HLH. All patients were followed up until death or 31 Dec 2018, whichever occurred first. Patients undergoing stem cell transplantation were censored on the date of that procedure. Results: There were 68 patients in total. The median age of the patients was 48 years (15-76 years). They were divided into two groups according to weather the initial treatment containing etoposide. There were 53 patients with initial etoposide and 15 without it. The baseline level between two group shows no differences (p>0.05). The treatment regimens with initial etoposide include HLH-94/04 regimen, DEP (doxorubicin-etoposide-methylprednisolone), L-DEP (PEG-aspargase and DEP regimen), E-CHOP (etoposide and CHOP regimen) and RE-CHOP; those without the initial etoposide, but high-dose chemotherapy, include CHOP/COP, R-CHOP/COP, L-CHOP, CVAD, L-GDP regimen and et al. The response rates of the 68 patients was 66.1%, with the CR rate of 25% (17/68) and PR rate of 41.1% (28/68). A total of 32 cases with initial etoposide achieved remission, and the remission rate was 71.7% (CR 28.3% and PR 43.4%). 7 cases with chemotherapy without etoposide achieved remission, and the remission rate was 46.7%. A significant difference was noted between the two groups (p<0.01). A total of 41 deaths occurred with a total mortality rate of 60.3%. There were 28 deaths in patients with initial etoposide (mortality rate 52.8%) and 13 deaths in the other group (mortality rate 86.6%). A significant difference in mortality was noted between the two groups (p=0.020). Comparing the long-time survival between two groups, the survival of the initial etoposide group (101w±13, 95%CI [76, 127]) is significantly better than that of the no initial etoposide group(37w±12.7, 95% CI [12.0, 61.9]) (p=0.43) (Figure 1). Conclusion: As one of the secondary HLHs, LAHS suffers the worst outcome among all the types of HLH. This study found that initial treatment including etoposide, comparing with the chemotherapy without etoposide, can provide higher response rate, lower mortality rate and better survival. Figure 1 Disclosures No relevant conflicts of interest to declare.

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The Outcome of 129 Korean Children with Hemophagocytic Lymphohistiocytosis.

Blood ◽

10.1182/blood.v108.11.3847.3847 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3847-3847

Author(s):

Hoi Soo Youn ◽

Joon Sup Song ◽

Ho Joon Im ◽

Jong Jin Seo ◽

Hyung Nam Moon ◽

...

Keyword(s):

Prognostic Factors ◽

Diagnostic Criteria ◽

Hemophagocytic Lymphohistiocytosis ◽

Initial Treatment ◽

Disease State ◽

Cns Involvement ◽

Hematopoietic Stem ◽

Korean Children ◽

Female Ratio ◽

Excellent Outcome

Abstract Chemotherapy and immunotherapy based treatments improved survival of patients with hemophagocytic lymphohistiocytosis(HLH), but the outcome is still unsatisfactory. We analyzed the putative prognostic factors in a nationwide cohort of patients with HLH. Retrospective data recruitment for the patients diagnosed as HLH during the past 10-year period from 1996 to 2005 was carried out by the Histiocytosis Working Party of the Korean Society of Hematology. The HLH diagnostic criteria of the Histiocyte Society were strictly applied to confirm the eligibility of patients for this study. We analyzed the outcome of pediatric patients with HLH according to the age at diagnosis, sex, central nervous system(CNS) involvement, disease condition(familial or secondary), treatment modalities and disease state after 2 months of initial treatment. One hundred twenty nine patients from 19 centers fulfilled the diagnostic criteria(n=112) and/or had affected siblings together with some of the criteria(n=17). The male to female ratio was 0.95:1. The probability of 3 year overall survival(OS) in HLH patients was 41% with a median follow-up of 51 months. The 3 year OS in patients under 12 months of age at presentation(n=23) was 21.7%, and 44.3% in those over 12 months of age(n=106)(p=0.001). The 3 year OS in patients with CNS involvement(n=16) was 29.1%, and 44.4% in patients without CNS involvement(n=112)(p=0.01). The 3 year OS in patients with active state after 2 months of initial treatment(n=63) was 14.1% compared to 77.2% in those with inactive state(n=61)(p=0.0001). The 3 year OS in patients who received hematopoietic stem cell transplantation(HSCT)(n=17) was 82.3%, and 35.2% in patients treated with chemoimmunotherapy only(n=112)(p=0.03). Among the HSCT patients, complete remission was obtained in 14 patients except 3 other patients who died of infection and graft failure at early post-transplant period. The reasons for HSCT were active disease after chemoimmunotherapy(n=8), relapsed disease(n=5), and familial HLH(n=4). Other prognostic factors were not significantly correlated with outcome in our survey. The age and CNS involvement at diagnosis, disease state after 2 months of initial treatment were important prognostic factors which affected the outcome of HLH significantly in this cohort. This survey also demonstrated excellent outcome of familial or relapsed, persistent secondary HLH after HSCT compared to chemoimmunotherapy only.

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Changes in Cytokine Profile during Initial Treatment of Pediatric Hemophagocytic Lymphohistiocytosis Associated with Epstein-Barr Virus

Journal of Nippon Medical School ◽

10.1272/jnms.jnms.2020_87-307 ◽

2020 ◽

Vol 87 (3) ◽

pp. 166-170

Author(s):

Takahiro Ueda ◽

Toshikazu Itabashi ◽

Shingo Yamanishi ◽

Yujiro Tanabe ◽

Makoto Migita ◽

...

Keyword(s):

Hemophagocytic Lymphohistiocytosis ◽

Initial Treatment ◽

Epstein Barr Virus ◽

Cytokine Profile ◽

Barr Virus ◽

Epstein Barr

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Requirement for containing etoposide in the initial treatment of lymphoma associated hemophagocytic lymphohistiocytosis

10.21203/rs.3.rs-40791/v2 ◽

2020 ◽

Author(s):

Yue Song ◽

Jingshi Wang ◽

Yini Wang ◽

Lin Wu ◽

Zhao Wang

Keyword(s):

Hemophagocytic Lymphohistiocytosis ◽

Initial Treatment ◽

Standard Treatment ◽

Response Rate ◽

Remission Rate ◽

Group 14 ◽

Ebv Infection ◽

Inflammatory Status ◽

Cox Analysis ◽

Better Than

Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory status caused by a hereditary or acquired immunoregulatory abnormality. Lymphoma associated hemophagocytic lymphohistiocytosis (LAHS) is a kind of secondary HLH (sHLH). It has the worst prognosis among sHLH. However, there’s still no standard treatment strategy. The argument mainly focuses on whether an HLH-directed or malignancy-directed approach should initially be adopted. Etoposide is one of the key drugs in HLH treatment, also effective in lymphomas. We sought to identify the importance of containing etoposide in initial treatment, comparing with the chemotherapy which directed at lymphoma but without etoposide. Methods: 66 patients diagnosed as LAHS in our center between Jan 1 2015 and Dec 31 2017 were divided into two groups according to weather the initial treatment containing etoposide, or other lymphoma-directed chemotherapy without etoposide. Results: The remission rate of the initial etoposide group (52 patients) is significantly better than that of no initial etoposide group (14 patients) (73.1% vs. 42.9%, p=0.033). The 2-month survival rate (79.8% vs. 46.8%, p=0.035) and overall survival (median survival time 25.8w vs. 7.8w, p=0.048) of the initial etoposide contained group is significantly better. Multivariate cox analysis revealed that for patients without EBV infection (37 cases), initial treatment with etoposide could significantly improve prognosis (p=0.010, Exp(B)=0.183), but for patients with positive EBV, it’s not significant. Conclusions: Containing etoposide is beneficial in the initial treatment of LAHS, weather using the HLH directed or lymphoma directed strategy. It provides higher response rate, lower mortality rate and better survival, especially for EBV negative patients.

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Requirement for Containing Etoposide in the Initial Treatment of Lymphoma Associated Hemophagocytic Lymphohistiocytosis

10.21203/rs.3.rs-40791/v1 ◽

2020 ◽

Author(s):

Yue Song ◽

Jingshi Wang ◽

Yini Wang ◽

Lin Wu ◽

Zhao Wang

Keyword(s):

Mortality Rate ◽

Hemophagocytic Lymphohistiocytosis ◽

Initial Treatment ◽

Standard Treatment ◽

Remission Rate ◽

Group 14 ◽

Inflammatory Status ◽

Significant Difference ◽

Cox Analysis ◽

Better Than

Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory status caused by a hereditary or acquired immunoregulatory abnormality. Lymphoma associated hemophagocytic lymphohistiocytosis (LAHS) is a kind of secondary HLH (sHLH). It has the worst prognosis among sHLH. However, there’s still no standard treatment strategy. The argument mainly focuses on whether an HLH-directed or malignancy-directed approach should initially be adopted. Etoposide is one of the key drugs in HLH treatment, also effective in lymphomas. We sought to identify the importance of containing etoposide in initial treatment, comparing with the chemotherapy which directed at lymphoma but without etoposide. Methods: 66 patients diagnosed as LAHS in our center between Jan 1 2015 and Dec 31 2017 were divided into two groups according to weather the initial treatment containing etoposide, or other lymphoma-directed chemotherapy without etoposide. Results: The remission rate of the initial etoposide group (52 patients) is significantly better than that of no initial etoposide group (14 patients) (73.1% vs. 42.9%, p = 0.033). The relapse occurrence between two groups shows difference (26.3% vs. 50%) but not significant (p = 0.339). There were 28 deaths in patients with initial etoposide (mortality rate 53.8%) and 12 deaths in the without-initial-etoposide group (mortality rate 85.7%). A significant difference in mortality was noted between the two groups (p = 0.030). The 2-month survival (79.8% vs. 46.8%, p = 0.019) and overall survival (median survival time 25.8w vs. 7.6w, p = 0.048) of the initial etoposide contained group is also better. Multivariate cox analysis revealed that for patients without EBV infection (37 cases), initial treatment with etoposide could significantly improve prognosis (p = 0.010, Exp(B) = 0.183), but for patients with positive EBV, it’s not significant. Conclusions: We concluded that containing etoposide is essential in the initial treatment of LAHS, weather using the HLH directed or lymphoma directed strategy. It provides higher response rate, lower mortality rate and better survival, especially for EBV negative patients.

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