scholarly journals Radiation dose reduction for patients with extranodal NK/T-cell lymphoma with complete response after initial induction chemotherapy

2016 ◽  
Vol Volume 9 ◽  
pp. 5875-5881 ◽  
Author(s):  
Liang Wang ◽  
Xi-wen Bi ◽  
Zhong-jun Xia ◽  
Hui-qiang Huang ◽  
Wen-qi Jiang ◽  
...  
Keyword(s):  
T Cell ◽  
Radiation Dose ◽  
Dose Reduction ◽  
Induction Chemotherapy ◽  
Cell Lymphoma ◽  
Complete Response ◽  
Radiation Dose Reduction ◽  
T Cell Lymphoma ◽  
Nk T Cell

The Efficacy of Bortezomib-CHOP In Patients with Advanced Stage T or NK/T Cell Lymphomas: The Results of Multicenter Phase II Study.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1791-1791 ◽  
Author(s):  
Seok Jin Kim ◽  
Hyeon-Seok Eom ◽  
Jin Seok Kim ◽  
Hye Jin Kang ◽  
Hyo Jung Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Advanced Stage ◽  
Chop Regimen ◽  
T Cell Lymphomas ◽  
Nk T Cell

Abstract Abstract 1791 Background Advanced stage T-cell or NK/T-cell lymphomas usually show aggressive clinical course and their treatment outcomes are worse than B-cell non-Hodgkin lymphoma. Furthermore, the optimal treatment regimen is not still established for these disease entities. At present, cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen is still used as a primary treatment for advanced stage T or NK/T cell lymphomas although its efficacy is not satisfactory. Thus, more effective treatment regimen is required to improve treatment outcome. The incorporation of new targeted agents into CHOP regimen has been a widely used strategy to develop new regimen for the treatment of lymphoma. Bortezomib, a proteasome inhibitor approved for the use of treatment of multiple myeloma has been tried in many B-cell non-Hodgkin lymphomas. A recent in vitro study results showed that proteasome inhibitor could inhibit the growth of NK/T lymphoma cells. Based on these results, we designed a regimen combining CHOP with. Our previous phase I study determined the maximum tolerated dose of bortezomib as 1.6mg/m2 for combination with CHOP. Thus, we performed the phase II study to evaluate the efficacy of bortezomib plus CHOP chemotherapy. Methods We enrolled patients with newly diagnosed T or NK/T cell lymphoma. All patients were Ann Arbor stage III/IV and had adequate organ function. Patients received bortezomib on days 1 and 8 (weekly schedule, 1.6 mg/m2 per dose) in addition to 750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, 1.4 mg/m2 vincristine on day 1 and 100 mg/day prednisolone on days 1 to 5, every 3 weeks. Six cycles of therapy administered every 21 days were planned. All patients provided written informed consents and this trial was registered at www.ClinicalTrials.gov (NCT00374699). Results 46 patients were enrolled between April 2007 and August 2009. Peripheral T-cell lymphoma, unspecified (n=16) and extranodal NK/T cell lymphoma (n=10) were dominant subtypes while angioimmunoblastic T-cell lymphoma (n=8) and ALK-negative anaplastic large cell lymphoma (n=6) account for 30.4% of all patients. Five patients with cutaneous T-cell lymphoma and one hepatosplenic T-cell lymphoma were also recruited. The median age at diagnosis was 52 years (range 21 – 66 years). Serum LDH elevation (n = 28, 60.9%) and stage IV patients were dominant (n = 32, 69.6%). Thus, the International Prognostic Index risk was dominantly high or high-intermediate (n = 26, 56.5%). Complete response was achieved in 30 patients (65.2%) and partial response was 5 patients (10.9%). As a result, the overall response rate was 76.1%. The comparison of complete response rate based on the subtype demonstrated that the complete response rate of peripheral T-cell lymphoma, unspecified (12/19, 63.2%), angioimmunoblastic T-cell lymphoma (6/8, 75%), anaplastic large cell lymphoma (4/6, 66.7%) and cutaneous T-cell lymphoma (5/5, 100.0%) was better than extranodal NK/T cell lymphoma (3/10, 30.0%). Five patients with extranodal NK/T cell lymphoma progressed during the treatment with bortezomib and CHOP. The hematologic toxicity was the major toxicity of this regimen, thus, grade 3/4 leucopenia and febrile neutropenia were the most frequent toxicity. However, there was no treatment-related mortality. In addition, neurotoxicity was tolerable, so the majority of peripheral neurotoxicity was grade 1 or 2. Conclusion The combined treatment of bortezomib with CHOP is an effective regimen for advanced stage T-cell lymphomas with acceptable toxicity. However, it may not be efficient for advanced stage extranodal NK/T-cell lymphomas. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Optimizing Radiation Dose for Early-Stage Extranodal Nasal-Type NK/T-Cell Lymphoma

2016 ◽  
Vol 96 (2) ◽  
pp. S166-S167
Author(s):  
Y. Yang ◽  
J. Wu ◽  
T. Wu ◽  
S.Y. Zhu ◽  
L.T. Qian ◽  
...  
Keyword(s):  
T Cell ◽  
Radiation Dose ◽  
Cell Lymphoma ◽  
Early Stage ◽  
T Cell Lymphoma ◽  
Nasal Type ◽  
Nk T Cell

Concurrent Chemo-Radiotherapy Followed by VIDL (Etoposide, Ifosfamide, Dexamethasone, L-asparaginase) Chemotherapy In Stage I/II Extranodal NK/T-Cell Lymphoma of Nasal Cavity/Nasopharynx

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1765-1765
Author(s):  
Seok Jin Kim ◽  
Hyeon-Seok Eom ◽  
Jin Seok Kim ◽  
Jae-Yong Kwak ◽  
Deok-Hwan Yang ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Major Toxicity ◽  
Nk T Cell ◽  
Grade 3

Abstract Abstract 1765 Background Localized extranodal NK/T-cell lymphoma (ENKTL) mainly occurs in nasal and/or nasopharynx. Thus, ENKTL shows a poor response to anthracycline-based chemotherapy because of the frequent expression of a multidrug-resistant p-glycoprotein, radiotherapy for localized disease produces a higher complete response rate than chemotherapy. However, when ENKTL is treated with radiation alone, local and systemic failures are frequently observed. Therefore, our group previously reported the improved outcome of concurrent chemo-radiotherapy (CCRT) with weekly administration of cisplatin followed by systemic chemotherapy VIPD (etoposide, ifosfamide, cisplatin and dexamethasone). However, the grade 3/4 hematologic toxicity was the major toxicity of VIPD. Thus, in consideration of the risk of toxicity of VIPD, we designed VIDL (etoposide, ifosfamide, dexamethasone, and L-asparaginase) as adjuvant to CCRT. Because etoposide and ifosfamide are less affected by p-glycoprotein, and NK lymphoma cells are known as being sensitive to L-asparaginase, we expected VIDL regimen could be more effective and less toxic than VIPD. Methods Thirty-one newly diagnosed stage IE/IIE nasal/nasopharynx ENKTL patients received CCRT (radiation 40–50.4 Gy and cisplatin 30 mg/m2 weekly). Two cycles of VIDL (etoposide 100 mg/m2 D1–D3, ifosfamide 1200 mg/m2 D1–D3, dexamethasone 40 mg D1–D3, and L-asparaginase 4000IU/m2) were scheduled after CCRT. All patients provided informed written consents and this trial was registered at www.ClinicalTrials.gov (NCT01007526). Results The median age was 46.5 years (range, 22–71 years); 78.1% of all patients were younger than 60 years of age, and male (n = 21) to female (n = 11) was 2:1. Twenty-two patients were stage IE and nine were IIE. The majority of patients were in the low (n = 24) or low–intermediate (n = 6) risk categories of the International Prognostic Index. However, when we grouped patients based on the NK/T cell lymphoma prognostic index (NKPI) proposed previously for ENKTL, which includes the presence of B cell symptoms, lesions at stage III or IV, elevated serum LDH concentration, and lymph node involvement, 25 patients belonged to group I or II and 7 patients were group III or IV (those with more than two risk factors). All patients completed CCRT, which resulted in 90.3% overall response rate including 22 complete response (CR) and 6 partial response (PR). Twenty-seven patients completed the planned two cycles of VIDL while four patients did not because three patients progressed during or after CCRT, and one patient is ongoing. The overall response rate of 27 patients completed VIDL was 92.6%, and two patients relapsed after the completion of VIDL chemotherapy. The major toxicity of VIDL was grade 3/4 leucopenia (85.1%), but there was no treatment-related mortality. The non-hematologic toxicity was tolerable, and the hepatic toxicity-associated with the use of L-asparaginase was frequent (55.5%). However, the majority of the hepatic toxicities were grade 1 or 2. Conclusion Concurrent chemo-radiotherapy followed by VIDL chemotherapy can be an effective treatment strategy with acceptable toxicity in stage I/II extranodal NK/T-Cell lymphoma of nasal cavity/nasopharynx. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Final Report on Phase II Trial of L-Asparaginase Plus Concurrent Chemoradiotherapy Followed By Midle (Methotrexate, Ifosfamide, Etoposide, Dexamethasone, and L-asparaginase) Chemotherapy for Patients with Newly Diagnosed Stage I/II Extranodal NK/T-Cell Lymphoma, Nasal Type

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3942-3942
Author(s):  
Dok Hyun Yoon ◽  
Seok Jin Kim ◽  
Seong Hyun Jeong ◽  
Dong-Yeop Shin ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
T Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Nasal Type ◽  
Nk T Cell ◽  
Grade 3

Abstract Background We previously have shown that concurrent chemoradiotherapy (CCRT) followed by chemotherapy such as VIPD (etoposide, ifosfamide, cisplatin and dexamethasone) or VIDL (etoposide, ifosfamide, dexamethasone and L-asparaginase) is an effective treatment for the management of localized extranodal NK/T-cell lymphoma (ENKTL), nasal type. To further improve efficacy, we designed a new treatment protocol, MIDLE (methotrexate, ifosfamide, dexamethasone, L-asparaginase and etoposide), which incorporates tri-weekly administration of L-asparaginase during CCRT to reduce the probability of systemic progression and high dose methotrexate to intensify chemotherapy based on previous excellent outcomes of methotrexate-containing regimens such as SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) and MLD (methotrexate, L-asparaginase, dexamethasone). Methods The treatment scheme of CCRT consisted of radiation 36-45 Gy and weekly administration of cisplatin 30 mg/m2 (total: 4 doses). During the CCRT, tri-weekly 4,000 IU of Escherichia coli L-asparaginase was administered intravenously (IV). The chemotherapy, MIDLE (methotrexate 3 g/m2 on day 1, etoposide 100 mg/m2, Ifosfamide 1000 mg/m2 on day 2-3, dexamethasone 40mg on day 1-4, and L-asparaginase 6000 IU/m2 IV on day 4, 6, 8, 10) was repeated every 28 days for two cycles. All patients provided informed written consents and this trial was registered at www.ClinicalTrials.gov(NCT01238159). Results Twenty-eight patients with stage IE/IIE ENKTL were enrolled, and the median age was 51 years (range, 30-77 years). Twenty four patients were male while only four patients were female. Twenty-two patients had stage IE and six IIE disease. Twenty four were classified as low risk group and the other four intermediate group according to PINK-E (Kim SJ et al., EHA 2015 S110). All but two patients completed CCRT, which resulted in 85.7% of overall response rate including 16 complete responses (57.1%) and 8 partial responses (28.6%). One showed stable disease (SD) and the other one showed progressive disease (PD) with development of new distant lymph node involvement after CCRT. Grade 3 or 4 hematologic toxicity was not common. Only two patients experienced G3 neutropenia during or after CCRT. However, grade 3 non-hematologic toxicities were noted including bilirubin elevation (n = 3), mucositis (n = 1), anorexia (n=5) and nausea/vomiting (n = 11) Two could not complete CCRT according to the protocol due to G3 allergic reaction to L-asparaginase (n=1) and prolonged G3 mucositis (n=1). After the completion of CCRT, 23 out of 28 patients entered the MIDLE chemotherapy as five patients including one disease progression and four withdrawal during (n=2) or after (n=2) CCRT due to toxicities. All those who completed the planned two cycles of MIDLE chemotherapy achieved complete response after chemotherapy including those with PR (n=6) and SD (n=1) after CCRT. Three patients dropped out during or after their first cycle of MIDLE due to non-hematologic toxicities (recurrent G3 bilirubinemia (n=1), G3 increased creatinine (n=1), G5 infection (n=1)). The final complete response rate was 82% (23/28). It was associated with a significant rate of grade 3/4 neutropenia (n=21) and febrile neutropenia (n=10). Two patients experienced acute kidney injury (AKI) during the first cycle of MIDLE and one of them died of pneumonia complicated by sepsis. With a median follow-up of 46 months (95% confidence interval: 39 - 47 months), four patients progressed and five patients died with the estimated 3-year progression-free survival rate of 74.1% and overall survival rate of 81.5%. PINK-E could successfully stratify both time-to-progression (p=003) and overall survival (p=0.006) in this study. Conclusion L-asparaginase plus concurrent chemoradiotherapy followed by MIDLE chemotherapy may be an effective treatment strategy for stage I/II extranodal NK/T-Cell lymphoma, nasal type. However, higher numbers of patients were withdrawn during or after CCRT due to toxicity or poor tolerance than previous study. MIDLE chemotherapy was associated with high rate of G3 or 4 hematologic toxicities. Thus, this approach should be reserved for selected patients such as young fit but high risk of relapse. PINK-E can be a useful prognostic index for stage I/II extranodal NK/T-Cell lymphoma, nasal type. Disclosures No relevant conflicts of interest to declare.

Phase II Trial Of L-Asparaginase Plus Concurrent Chemoradiotherapy Followed By Midle (methotrexate, ifosfamide, etoposide, dexamethasone, and L-asparaginase) Chemotherapy For Patients With Newly Diagnosed Stage I/II Extranodal NK/T-Cell Lymphoma, Nasal Type

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3037-3037 ◽  
Author(s):  
Seok Jin Kim ◽  
Dok Hyun Yoon ◽  
Seong Hyun Jeong ◽  
Dong-Yeop Shin ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
T Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Nasal Type ◽  
Nk T Cell ◽  
Grade 3

Abstract Background The treatment of localized extranodal NK/T-cell lymphoma (ENKTL), nasal type has shifted to non-anthracycline-based intensive chemotherapy with radiotherapy since the poor response of ENKTL to anthracycline due to the expression of a multidrug-resistant (MDR) p-glycoprotein was proven. We previously proposed concurrent chemoradiotherapy (CCRT) followed by chemotherapy which is not affected by MDR and reported a significant improvement of outcomes of localized ENKTL. Based on our accumulated data, we designed a new treatment protocol. First, we added tri-weekly administration of L-asparaginase to reduce the probability of systemic progression during CCRT. Second, we designed MIDLE (methotrexate, ifosfamide, etoposide, dexamethasone, and L-asparaginase) according to previous excellent outcomes of methotrexate-containing regimens such as SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) and MLD (methotrexate, L-asparaginase, dexamethasone). Methods The treatment scheme of CCRT consisted of radiation 40 Gy and weekly administration of cisplatin 30 mg/m2 (total: 4 doses). During the CCRT, tri-weekly intravenous (IV) administration of 4,000 IU of Escherichia coli L-asparaginase was done. The chemotherapy, MIDLE (methotrexate 3g/m2 on day 1, etoposide 100mg/m2, Ifosfamide 1000mg/m2 on day 2-3, dexamethasone 40mg on day 1-4, and L-asparaginase 6000IU/m2 IV on day 4, 6, 8, 10) was repeated every 28 days up to 2 cycles. All patients provided informed written consents and this trial was registered at www.ClinicalTrials.gov(NCT01238159). Results Twenty-eight patients with stage IE/IIE ENKTL were enrolled, and the median age was 51 years (range, 30–77 years). 24 patients were male while only four patients were female. Twenty-two patients were stage IE and six were IIE. All patients completed CCRT, which resulted in 92.9% of overall response rate including 20 complete responses and 6 partial responses. One patient showed stable disease after CCRT whereas the other patient progressed. No grade 3 or 4 hematologic toxicity was found during CCRT. However, grade 3 non-hematologic toxicities included bilirubin elevation (n = 4), mucositis (n = 1), and nausea/vomiting (n = 6). After the completion of CCRT, 23 patients entered the MIDLE chemotherapy as five patients including one disease progression and four cases of withdrawal could not receive MIDLE. All patients achieved complete response after they completed the planned two cycles of MIDLE chemotherapy whereas two patients dropped out after their first cycle due to non-hematologic toxicity. The final complete response rate of patients enrolled was 92.9% (26/28). The major toxicity of MIDLE was grade 3/4 leucopenia, and the non-hematologic toxicity included mucositis and nausea/vomiting. The hepatic toxicity-associated with L-asparaginase was frequent. However, the majority of the hepatic toxicities were grade 1 or 2. With the median potential follow-up of 25 months (95% confidence interval: 19 – 31 months), four patients relapsed. Conclusion L-asparaginase plus concurrent chemoradiotherapy followed by MIDLE chemotherapy can be an effective treatment strategy with acceptable toxicity in stage I/II extranodal NK/T-Cell lymphoma, nasal type. Disclosures: Kwak: celgene: Research Funding.

The efficacy of PEG-Asp-argase-based chemotherapy for nasal-type extranodal NK/T-cell lymphoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19504-e19504
Author(s):  
Jing-Yun Wen ◽  
Mai Li ◽  
Xing Li ◽  
Qu Lin ◽  
Min Dong ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Cell Lymphoma ◽  
Complete Response ◽  
Invasive Disease ◽  
Bone Marrow Suppression ◽  
T Cell Lymphoma ◽  
Chop Regimen ◽  
Nasal Type ◽  
Nk T Cell

e19504 Background: Nasal-type extranodal NK/T-cell lymphoma (ENKL) is a highly invasive disease with quite poor prognosis.Pegaspargase (PEG-Asp) displays a similar anti-cancer mechanism as that of L-asparaginase (L-ASP), but exhibits lighter antigenicity. The aim of the present research was to evaluate efficacy and safty of PEG-Asp-based regimen in ENKL. Methods: Data were collected from 23 patients with histologically confirmed ENKL who were admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to March 2012. Each patient received PEG-Asp 2500 IU/m2/IM on day 1 of each 21-day chemo-cycle. Among them, 8 received combination chemotherapy with CHOP regimen, 11 with EPOCH, and 4 with a CHOP-like regimen (CHOP + bleomycin). The CHOP regimen consisted of cyclophosphamide 750mg/m2, IV (day 1), pirarubicin 40mg/m2, IV (day 1), vincristine 1.4 mg/m2, IV (day 1), and prednisone 100mg, oral (days 1- 5). The EPOCH regimen consisted of etoposide 50mg/m2, epidoxorubicin 12 mg/m2 and vincristine 0.4mg/m2 dissolved in 500mL saline and administered as a continuous IV drip for 24 hours on days 1- 4. Cyclophosphamide 750mg/m2, IV (day 5) and prednisone 60mg/m2, oral (days 1-5), were also administered. In the CHOP-like regimen, bleomycin 15mg was added on days 1-3. Stage I-II patients received local radiotherapy after the chemotherapy. Results: The patients received the PEG-Asp-based chemotherapy for 2-5 cycles (median, 4 cycles). Eleven (47.8%) achieved complete response (CR), and the overall response rate (ORR) was 82.6%. The median time to progression (TTP) was 5 months (range, 2-6 months) and the median OS was 16 months (range, 5-38 months). The 1-year and 2-year survival rate were 82.6% (19/23) and 56.5% (13/23) , respectively. A minor glutamic-pyruvic transaminase (GPT) elevation was observed in 3 patients (13.0%), slight decrease of albumin in 3 (13.0%), reduced fibrinogen level in 2 (8.7%), grade I-II WBC bone marrow suppression in 8 (34.8%), and grade III-IV WBC bone marrow suppression in 3 (13.0%). No allergic incidences were witnessed. Conclusions: Our results suggested PEG-Asp-based chemotherapy presented potential effects in treating nasal-type ENKL with acceptable side effects profile.

scholarly journals Related Adverse Events after Immunotherapy in Patient with NK/T-Cell Lymphoma: a Case Report

2021 ◽  
Vol 8 (7) ◽  
Author(s):  
Linlin Zhang ◽  
◽  
Xiaodong Wu ◽  
Miaomiao Xu ◽  
Wenbin Guan ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Cell Lymphoma ◽  
Pulmonary Inflammation ◽  
Single Agent ◽  
Complete Response ◽  
Lymphoid Cells ◽  
T Cell Lymphoma ◽  
Laryngeal Edema ◽  
Nk T Cell

A 29-year-old male with pathologically confirmed extranodal NK/T cell lymphoma of the tonsil, nasal type was admitted to Xinhua hospital affiliated to Shanghai Jiao Tong University School of Medicine. The patient was provided with several cycles of anti-PD-1 immunotherapy and obtained a Complete Response (CR) outcome. Despite the response, the patient also suffered from severe adverse effects, including a worsening pulmonary inflammation and severe laryngeal edema. A tracheotomy was performed to remove the white pseudo-membrane of laryngeal. via pathological analysis, necrosis of granuloma lymphoid cells and rhabdomous granuloma was found in this removed section. Meantime, a large amount of Candida nivaria, Klebsiella pneumoniae, and carbapenem-resistant Enterobacter was present in the patient’s sputum culture. The level of inflammatory cytokines (e.g., TNF-a, IL-1, IL-6, IL-17 and IFN-γ,) also increased significantly, indicating immune-related adverse events. Subsequently, the doctors adjusted immunotherapy to single-agent chemotherapy with additional anti-fungal and anti-bacterial infection treatment. The infection was well under control after these adjustments. 18F-FDG PET/ CT recorded the series of changes in the course of the patient from the start of immunotherapy.

Long-term survival of the nasal NK/T cell lymphoma

2008 ◽  
Vol 149 (17) ◽  
pp. 801-805
Author(s):  
Péter Rajnics ◽  
László Krenács ◽  
András Kenéz ◽  
Zoltán Járay ◽  
Enikő Bagdi ◽  
...  
Keyword(s):  
T Cell ◽  
Treatment Guidelines ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Diagnostic Procedures ◽  
T Cell Lymphoma ◽  
Term Survival ◽  
Barr Virus ◽  
Significant Difference ◽  
Nk T Cell

The nasal NK/T cell lymphoma is a rare, extranodal non-Hodgkin lymphoma in western civilizations, which has poor prognosis. The Epstein–Barr virus can be detected in tumor cells in nearly all cases. There are no definite treatment guidelines in our days. There is no significant difference in survival between radiotherapy and chemotherapy according to Asian studies. In this case study we show our diagnostic procedures, our treatment options and we present the summary of this illness based on the data found in the literature.

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