​Kembara Xtra - Medicine - Hodgkin Lymphoma

​Kembara Xtra - Medicine - Hodgkin Lymphoma 
Hodgkin lymphoma (HL) is a lymphatic system tumor and one of the most prevalent cancers in young adults. It is distinguished by a small number of malignant B lymphocyte-derived cells and a significant inflammatory microenvironment.

Background information:
– Thomas Hodgkin originally wrote about a group of six patients in 1832 who had clinical signs that were distinct from those of inflammation, syphilis, and tuberculosis. –
The enormous "Reed-Sternberg" (RS) cells, the microscopic indicators of Hodgkin lymphoma, were described independently by German pathologist Carl Sternberg (1898) and American pathologist Dorothy Reed (1902).
– Initially treated in the 19th century with herbs, surgery, and arsenic; observed to contract when exposed to x-rays at the start of the 20th century – Chemotherapy was implemented as first-line therapy in the early 1970s with the introduction of two different regimens: ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine), and MOPP (mechlorethamine, vincristine [Oncovin], procarbazine, and prednisone); noted to have remission rates of 80–90%.
two subtypes
95 percent of cases of Hodgkin lymphoma (cHL) had nodular sclerosing, mixed cellularity, lymphocyte rich or lymphocyte deficient patterns. 5% of cases of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)

Epidemiology 

 Has a bimodal age distribution—between 20 and 40 years and a second peak at about 55 years; typically diagnosed at age 20 to 34 years with median age 39 years at diagnosis given decreasing bimodal age distribution; incidence: 2 to 3 per 100,000 per year; predominance: 11% of all lymphoid malignancies;
1.3:1 is the male-to-female ratio.

Pathophysiology and Etiology 
cHL is a germinal center-derived B-cell lymphoma that no longer exhibits the B-cell characteristic.
RS cells include clonal rearrangements of immunoglobulin genes that are class-switched and hypermutated, resulting in immunoglobulin genes that are not functional and do not express the cell surface B-cell receptor. This should cause apoptosis in a healthy B cell, but in HL, these cells seem to be "rescued" from apoptosis by further oncogenic processes.
Although NLPHL lacks the usual RS cells, it does contain lymphocytic and histiocytic cells, which are distinguished by bigger cells with folding multilobulated nuclei (also known as "popcorn cells" or LP cells) and a nucleus with many nucleoli that are basophilic and smaller than RS cells.
Genome-wide association studies discovered 19p13.3 at TCF3's intron 2.
Genetics
First-degree kin: 3–9 times risk
Siblings of patients who are younger: 7 times risk
There is only a weak connection between familial HL and HLA class I regions encompassing the alleles HLA-A1, HLA-B5, HLA-B8, and HLA-B18.

Epstein-Barr virus (EBV) is found in approximately 45% of individuals with HL, suggesting that genetics may play a role in the disease. Risk factors include HIV, which increases the risk of HL in people who are HIV positive.

Presenting History Pel-Ebstein (cyclic) fever, a high-grade fever that occurs every 7 to 10 days, painless supraclavicular lymphadenopathy, and constitutional symptoms (sometimes known as "B symptoms"), such as intense night sweats, significant weight loss, exhaustion, and anorexia 
There may be persistent itching.
A mass may appear on a chest radiograph if the mediastinal lymphadenopathy is substantial, which can cause chest pain and shortness of breath.

clinical assessment 

 70% lymphadenopathy, firm, rubbery consistency (axillary, supraclavicular, and cervical). 
Splenomegaly might exist.
There may be hepatomegaly.

There could be tonsillar hypertrophy.

Multiple Diagnoses 
non-HL, solid tumor metastases, sarcoidosis, syphilis, TB, syphilis, syphilis, autoimmune illness, and medication reaction 

Laboratory Results 
Initial Tests (lab, imaging) LFT, LDH, ESR, HIV, EBV, and HCV Comprehensive metabolic panel, CBC with differential—may be linked with eosinophilia
Chest x-ray, computed tomography (CT) with contrast of the chest, abdomen, and pelvis, pulmonary function tests (PFTs), DLCO measurement in advance of treatment with bleomycin, and pregnancy testing for women of childbearing age. Positron emission tomography (PET) is used for initial staging, midtreatment decision-making, and end-of-treatment evaluation. Tests in the Future & Special Considerations
● Precautions for conception:
Considerations for radiation therapy (RT) include: - In vitro fertilization or ovarian tissue/oocyte cryopreservation - Semen cryopreservation if chemotherapy or pelvic radiation therapy (RT)
Pneumococcal, Haemophilus influenzae, and meningococcal vaccines for splenic RT Aspects of Geriatrics
Recommend careful treatment selection due to a worse prognosis if present before age 60: 
Less likely to endure harsh chemotherapy and be enrolled in research trials
Child Safety Considerations
Breast cancer is highly likely to develop in young girls (30 years of age) after thoracic radiation therapy, hence early breast cancer screening is advised.
pregnant women's issues
Using abdominal ultrasonography, subdiaphragmatic illness can be identified.
- If asymptomatic and in an early stage, wait till after delivery.
- Fetal malformation risk is decreased when ABVD is taken in the second and third trimesters, when it is more likely to produce abnormalities in the first trimester.
- Vinblastine monotherapy for symptom management


Diagnostic Procedures/Other Lumbar puncture and brain MRI if neurologic symptoms Immunohistochemistry Bone marrow biopsy if cytopenia with negative PET Excisional/incisional lymph node biopsy  

Interpretation of Tests
Morphology: Popcorn cells are observed in NLPHL, and RS cells in cHL are described as having a "owl eye" look with two nucleoli in two independent nuclear lobes. Immunophenotype: CD15+, CD30+, CD45+, CD3+ (T-cell marker), and typically CD20+
No consistent or distinct karyotypic findings in cytogenetics

Management: Cotswold modification and Ann Arbor staging Stage I: involvement of a single lymph node or extralymphatic organ or site; Stage II: involvement of two or more lymph node regions on the same side of the diaphragm; Stage III: node groups on both sides of the diaphragm; Stage IV: dissemination involving extranodal organs (with the exception of the spleen, which is considered lymphoid tissue).
- Classes: A indicates no systemic symptoms, B indicates systemic symptoms (fever, night sweats, weight loss of more than 10% of body weight), and X indicates a bulky disease (>1/3 intrathoracic diameter or >10-cm nodal mass).
The goal of treatment is cure
All suggestions for additional medical care and therapy are based on National Comprehensive Cancer Network (NCCN) consensus. Refer to the NCCN Practice Guidelines in Oncology for Hodgkin lymphoma for more information.

First Line of Medicine
Advanced stage disease: chemotherapy. PET/CT utilized after cycle 2 (PET-2) to guide either escalation or deescalation of therapy. Early stage disease: combined modality treatment with chemotherapy/radiotherapy or chemotherapy.
– ABVD:
 Severe phlebitis requires the use of a central line for therapy  Extremely emetogenic
Vinblastine: neuropathy risk
Bleomycin can cause mortality and lung toxicity; a test dosage may be given before the first cycle.
Doxorubicin may cause cardiotoxicity; keep an eye on the LVEF.
- AAVD (doxorubicin, brentuximab vedotin, vinblastine, and dacarbazine), an anti-CD30 chimeric antibody conjugated to a synthetic antimicrotubule agent:  According to the ECHELON-1 experiment, better than ABVD (2)  Preferable, particularly if PFTs are abnormal
 Brentuximab vedotin: diarrhea, neutropenia, tiredness, nausea, and peripheral neuropathy 

Next Line
Saved for individuals with relapsed/refractory (R/R) diseases 
The following factors affect the therapeutic approach and order of treatments: autologous stem cell transplant (ASCT) eligibility, functional response to salvage chemotherapy, length of remission, prior therapy, and comorbidities. 
Standard: high-dose therapy (HDT) with ASCT +/ ISRT is utilized after the initial treatment with no chemotherapeutic drugs.
Nivolumab (anti-PD1) in a phase 2 study of R/R cHL demonstrated ORR 69% with sustained response and favorable safety profile. Pembrolizumab (anti-PD1) is FDA approved for patients with R/R cHL who have failed two or more lines of treatment.

 Third-line new medicines being studied include immunomodulators (lenalidomide), proteosome inhibitors (everolimus), and mammalian target of rapamycin (mTOR) inhibitors. In patients who had received extensive pretreatment, CAR T-cell therapy targeted to CD30 observed significant rates of persistent response.

If second-line therapy, such as HDT/ASCT, is unsuccessful, the median survival is three years. NLPHL is treated with rituximab plus CHOP (CD20 positive).

Surgical Techniques 

To begin with, a lymph node biopsy after excision is advised.

Admission 
installation of a central venous catheter for delivery of chemotherapy

Constant Care 
Patients receiving ABVD treatment develop neutropenia. Neutropenia does not clearly enhance the risk of infection during treatment, growth factors or not.


Patient Follow-Up Monitoring
CBC, nutrition, and hydration are important during treatment. Restage with PET after two chemotherapy cycles is a sensitive prognostic predictor. - Laboratory studies: CBC, platelets, BMP, and ESR (if raised at the time of diagnosis), as clinically required - History and physical: every two years for the first two years, then every six to twelve months for the following year, and then annually  Thyroid stimulating hormone (TSH) once a year if neck radiation - Imagery
 PET-CT must show negative within 3 months of treatment completion to document "Complete Response"; annual surveillance PET is not necessary.
 CT scans should only be performed when clinically necessary or every six months for the first two years.  Beginning 8 to 10 years following therapy or at age 40 (whichever comes sooner), get a breast mammography every year. According to the American Cancer Society, if chest or axillary radiation (annual breast MRI as well if initially exposed between ages 10 and 30 years) - An annual flu shot - A referral for cancer survivorship with psychosocial support - Smoking cessation: Smoking and chest radiation greatly increase the risk of lung cancer.

Patient education, reproductive effects, and risks of subsequent cancers

Prognosis: cHL is 85% curable.
Relapse or illness progression rate: 5-20%
Rates of overall survival:
- 92% survive for one year.
- 5-year survival rate: 87 percent (93% if localized)
- 80% survive 10 years.
For advanced disease, the international prognostic score is: >45 years of age
- Gender: Male
Lymphocytopenia: 600 lymphocyte cells/dL or lymphocytes 8% of WBC; Albumin 4 g/dL; Hemoglobin 10.5 g/dL; WBC 15,000 cells/dL; Stage IV disease

Complications 

Late complications: Radiation exposure and the usage of anthracyclines both raise the risk of cardiovascular and valvular disease. Patients may experience peripheral neuropathy after therapy.
Irreversible lung damage brought on by bleomycin use
The possibility of developing secondary cancers, such as myeloid neoplasms from alkylating chemicals and breast cancer from radiation exposure.

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