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Hodgkin’s lymphoma Rakesh Biswas MD, Professor, Department of Medicine, People's College of Medical Sciences, Bhanpur, Bhopal, India.

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Presentation on theme: "Hodgkin’s lymphoma Rakesh Biswas MD, Professor, Department of Medicine, People's College of Medical Sciences, Bhanpur, Bhopal, India."— Presentation transcript:

1 Hodgkin’s lymphoma Rakesh Biswas MD, Professor, Department of Medicine, People's College of Medical Sciences, Bhanpur, Bhopal, India

2 A 25 year old lady 1 month of evening rise of temperature, night sweats and noticed a lump in her neck On examination pallor, generalized lymphadenopathy, hepatosplenomegaly

3 I wasn't feeling well, still couldn't shake the cold that had been plaguing me for what seemed like months. But all in all, not feeling too bad, either.

4 It is required that anybody teaching in the schools have a clear tuberculosis record. After waiting several minutes, the nurse read my test site. She said it seemed to her there was a little swelling that shouldn't be there, and she asked me to wait and see the doctor.

5 I started to get a little bit nervous, I mean, Tuberculosis? Was that possible? The doctor brought me into her room and she examined me, and she said she could feel tumors in my neck. Had I noticed them?

6 Lymphoma Clonal malignant disorders that are derived from lymphoid cells: either precursor or mature T-cell or B-cell Clonal malignant disorders that are derived from lymphoid cells: either precursor or mature T-cell or B-cell Majority are of B- cell origin Majority are of B- cell origin Divided into 2 main types : Divided into 2 main types : 1. Hodgkin’s lymphoma 1. Hodgkin’s lymphoma 2. Non - Hodgkin’s lymphoma 2. Non - Hodgkin’s lymphoma

7 Hodgkin’s Disease Histologically & clinically a distinct malignant disease Histologically & clinically a distinct malignant disease Predominantly, B-cell disease Predominantly, B-cell disease Course of the disease is variable, but the prognosis has improved with modern treatment Course of the disease is variable, but the prognosis has improved with modern treatment

8 Etiology ? Infection – EBV ? Infection – EBV ? Environmental factors ? Environmental factors

9 REAL* Classification Classic: Nodular Sclerosis Nodular Sclerosis Lymhocyte rich Lymhocyte rich Mixed Cellularity Mixed Cellularity Lymhocyte depleted Lymhocyte depleted Non-Classic Nodular Lymphocyte predominant Nodular Lymphocyte predominant *REAL – Revised European,American,lymphoma

10 Clinical features distribution : Bimodal age distribution : young adults ( yrs) & elderly (> 50yrs) May occur at any age young adults ( yrs) & elderly (> 50yrs) May occur at any age M > F M > F Lymphadenopathy: Lymphadenopathy: most often cervical region most often cervical region asymmetrical, discrete asymmetrical, discrete painless, non-tender painless, non-tender elastic character on palpation ( rubbery) elastic character on palpation ( rubbery) not adherent to skin not adherent to skin fluctuate in size fluctuate in size

11 Contiguous spread via the lymphatic chain eg.involvement of abdominal & thoracic LNs Contiguous spread via the lymphatic chain eg.involvement of abdominal & thoracic LNs Extra nodal disease - rare Extra nodal disease - rare Hepatospleenomegaly Hepatospleenomegaly

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13 Constitutional symptoms ( ) Constitutional symptoms ( B symptoms ) Night sweats, Night sweats, sustained fever > 38 degree celsius, sustained fever > 38 degree celsius, loss of weight >10% of body weight in 6 mo loss of weight >10% of body weight in 6 mo Fever sometimes cyclical Fever sometimes cyclical (‘Pel-Ebstein fever’) Pain at the site of disease after drinking alcohol Pain at the site of disease after drinking alcohol Pallor Pallor Pruritis Pruritis Symptoms of Bulky (>10 cm) disease Symptoms of Bulky (>10 cm) disease

14 A zillion tests were done, blood drawn a zillion times, a zillion questions by a million doctors. Finally it was decided they would have to perform a biopsy on one of the tumors to get a diagnosis.

15 Investigations CBP : Anemia ( normochromic / normocytic), eosinophilia, neutrophilia, lymphopenia CBP : Anemia ( normochromic / normocytic), eosinophilia, neutrophilia, lymphopenia ESR -raised ESR -raised LFT- (liver infil / obs at porta hepatis) LFT- (liver infil / obs at porta hepatis) RFT- prior to treatment RFT- prior to treatment Urate, Ca, Urate, Ca, LDH - adverse prognosis LDH - adverse prognosis CXR- mediastinal mass CXR- mediastinal mass CT thorax / abdomen / pelvis-for staging CT thorax / abdomen / pelvis-for staging Other: Gallium scan, PET, Lymphangiography, Laporotomy Other: Gallium scan, PET, Lymphangiography, Laporotomy

16 LN FNAC / biopsy : LN FNAC / biopsy : Malignant : Bi- nucleate cell with a prominent nucleolus. Derived from B cell, at an early stage of differentiation Malignant REED-STERNBERG ( RS) Cell: Bi- nucleate cell with a prominent nucleolus. Derived from B cell, at an early stage of differentiation Reactive background of eosinophils, lymphocytes, plasma cells Reactive background of eosinophils, lymphocytes, plasma cells Fibrous tissue Fibrous tissue

17 The operation was done on February third, my boyfriend's birthday. I made him a card out of paper I had… Hard to celebrate your boyfriend's birthday while getting ready to get operated on.

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20 REED-STERNBERG ( RS ) Cell

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23 The X-ray technician came out again, looking for me. "We're not ready for you yet, the Doctors are still reading your chart, but we wanted to make sure you didn't leave. Just wait a few minutes and the doctor will be out to talk to you."

24 I've read in novels the expression "my heart sank" but I'm not sure I ever really felt that sort of thing until just about then. I'd been telling myself there was nothing to worry about, all was ok, but this was a clear cut sign that something was very. very wrong

25 >10 cm Bulky disease

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28 Lymphangiography

29 Staging : Involvement of single LN region (I) or extra lymphatic site (IA E ) Stage I : Involvement of single LN region (I) or extra lymphatic site (IA E ) Two or more LN regions involved (II) or an extra lymphatic site and lymph node regions on the same side of diaphragm Stage II : Two or more LN regions involved (II) or an extra lymphatic site and lymph node regions on the same side of diaphragm Involvement of lymph node regions on both sides of diaphragm, with (III E ) or without (III) localized extra lymphatic involvement or involvement of the spleen (II S ) or both (IIS E ) Stage III : Involvement of lymph node regions on both sides of diaphragm, with (III E ) or without (III) localized extra lymphatic involvement or involvement of the spleen (II S ) or both (IIS E ) Involvement outside LN areas (Liver, bone marrow) Stage IV : Involvement outside LN areas (Liver, bone marrow) A : Absence of ‘B’ symptoms A : Absence of ‘B’ symptoms B : B symptoms present B : B symptoms present

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31 I had Stage IVb Hodgkin's Disease, a form of cancer of the lymph nodes. Well, it's sort of hard to describe what hearing something like that does. It seemed impossible that the nodes in my neck, and the masses that were supposedly on my lungs were cancer. How could that be? I just was amazed. I said "this is unbelievable." and felt more or less detached, numb.

32 Treatment RT RT Chemo Chemo BMT / SCT BMT / SCT Antibody treatment: Rituximab target CD-20 Antibody treatment: Rituximab target CD-20 Supportive Supportive

33 Treatment - Guidelines Indications for RT: Stage I disease Stage I disease Stage II disease with 3 or lesser areas involved Stage II disease with 3 or lesser areas involved For Bulky disease For Bulky disease For pressure problems For pressure problems Indications for CT All with B symptoms All with B symptoms Stage II disease with >3 areas involved Stage II disease with >3 areas involved Stage III and IV disease Stage III and IV disease

34 Treatment : Radiotherapy Stage IA, Stage IIA with 3 or < 3 areas involved: Radiotherapy : Chemotherapy every 3-4 weeks, 6-8 cycles; either alone, or in combination with radiotherapy Stage IB, Stage II A with > 3 areas, Stage IIB: Chemotherapy every 3-4 weeks, 6-8 cycles; either alone, or in combination with radiotherapy Chemotherapy + Radiotherapy ( for bulky disease or palliation of symptoms) Stage III & IV : Chemotherapy + Radiotherapy ( for bulky disease or palliation of symptoms)

35 Irradiation fields used in Hodgkin’s Lymphoma

36 Chemotherapy Nitrogen Mustard, Vincristine (Oncovin), Procarbazine, Prednisolone MOPP : Nitrogen Mustard, Vincristine (Oncovin), Procarbazine, Prednisolone Adriamycin, Bleomycin, Vinblastine, Dacarbazine ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine Higher dose for relapse or younger pts with poor prognostic features Higher dose for relapse or younger pts with poor prognostic features

37 After six cycles of chemotherapy, my CT scans still show masses on my chest and in my neck. On July 7, I had a meeting with my doctors, and was told that if I continued with standard chemotherapy, my chances of being cured stand at less than ten per cent.

38 Prognosis Overall 10 yr survival – 80% Overall 10 yr survival – 80% In long term survivors there is a risk of In long term survivors there is a risk of secondary malignancy: (), Solid secondary malignancy: (leukemia, NHL), Solid tumors- Lung, breast Infections Infections Cardiac, pulmonary, endocrinal abnormalities Cardiac, pulmonary, endocrinal abnormalities

39 International Prognostic Index (IPI) Age Age Advanced stage disease Advanced stage disease Performance status Performance status Elevated LDH Elevated LDH Presence of Extra nodal disease Presence of Extra nodal disease

40 Non Hodgkin’s lymphoma Incidence is increasing Incidence is increasing NHL>HD NHL>HD Median age of presentation is yrs Median age of presentation is yrs M>F M>F More often clinically disseminated at diagnosis More often clinically disseminated at diagnosis B-cell-70% ; T-cell-30% B-cell-70% ; T-cell-30%

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42 ‘1990…Although I had been feeling fine, no different from normal, I was worried about this lump in my neck that I had for several months. I first thought it was just because I had some sort of infection, but it didn't go away.

43 Clinical features Widely disseminated at presentation Widely disseminated at presentation Nodal involvement: Painless lymphadenopathy, often cervical region is the most common presentation Nodal involvement: Painless lymphadenopathy, often cervical region is the most common presentation Hepatospleenomegaly Hepatospleenomegaly Extranodal : ( abdominal pain, anemia, dysphagia); CNS ( headache, cranial nerve palsies, spinal cord compression) ; Extranodal : Intestinal lymphoma ( abdominal pain, anemia, dysphagia); CNS ( headache, cranial nerve palsies, spinal cord compression) ; (low grade): Pancytopenia Skin, Testis; Thyroid; Lung Bone marrow (low grade): Pancytopenia

44  Systemic symptoms Sweating, weight loss, itching Sweating, weight loss, itching Metabolic complications: hyperuricemia, hypercalcemia, renal failure Metabolic complications: hyperuricemia, hypercalcemia, renal failure Compression syndrome: Compression syndrome: Gut obstruction Gut obstruction Ascites Ascites SVC obstruction SVC obstruction S/C Compression S/C Compression

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46 'The surgeon took a biopsy of the lump, taking a few cells out with a needle to be looked at under the microscope. When the results came back a few weeks later, he told me that they showed I had non-Hodgkin's lymphoma

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48 Diagnosis and staging Similar to HD Similar to HD plus, Bone marrow aspirate & trephine Bone marrow aspirate & trephine Immunophenotyping : Monoclonal antibodies directed against specific lymphocyte associated antigens B cell antigens ( CD 19, 20, 22); T cell antigens ( CD 2, 3, 5 & 7) Immunophenotyping : Monoclonal antibodies directed against specific lymphocyte associated antigens B cell antigens ( CD 19, 20, 22); T cell antigens ( CD 2, 3, 5 & 7) Immunoglobulin determination: Ig G / IgM praprotein marker Immunoglobulin determination: Ig G / IgM praprotein marker HIV HIV CT / MRI

49 Classification REAL REAL Clinical / Working Formulation Clinical / Working Formulation Low grade Low grade Inermediate grade Inermediate grade High grade High grade

50 Classification Low grade Proliferation: Low Course: Indolent Symptoms: -ve Treatment: Not curable High gradeHigh Rapid, fatal(un-Rx) +ve Potentially Curable Staging Similar to HD

51 Etiology Cannot be attributed a single cause Cannot be attributed a single cause Chromosomal translocations: t (14, 18) Chromosomal translocations: t (14, 18) Infection: Infection: Virus:EBV, HTLV,HHV-8, HIV Virus:EBV, HTLV,HHV-8, HIV Bacteria: H.Pylori - Gastric lymphoma Bacteria: H.Pylori - Gastric lymphoma Immunology: Immunology: Congenital immunodeficiency, Congenital immunodeficiency, Immunocompromised patients - HIV, organ transplantation Immunocompromised patients - HIV, organ transplantation

52 'When I went back a couple of weeks later, he said that the results showed I had stage I indolent follicular non- Hodgkin's lymphoma, which is a slow- growing form of the disease. He said that the good news was that only one lymph node was affected and that I had no B symptoms.

53 So, he suggested that I have radiotherapy on the swollen lymph node in my neck to make it go away. Because I had heard so many stories about how radiotherapy can make you sick and your hair fall out, I was quite worried

54 'In the end, I didn't have any real side effects, apart from feeling a bit tired, and the lump in my neck went away completely. After a check-up a couple of weeks later, the haematologist told me that I should come back every 6 months for another CT scan to make sure that the non-Hodgkin's lymphoma hadn't come back.

55 Management Low grade: Asymptomatic : No treatment ; Asymptomatic : No treatment ; Radiotherapy for localised disease (Stage 1); Radiotherapy for localised disease (Stage 1); Chemotheraphy: mainstay is Chlorambucil; Initial response good, but repeated relapses, median survival 6-10 yrs; Chemotheraphy: mainstay is Chlorambucil; Initial response good, but repeated relapses, median survival 6-10 yrs; Newer: Fludarabine, 2-CdA (Chlorodeoxyadenosine) Newer: Fludarabine, 2-CdA (Chlorodeoxyadenosine) Monoclonal antibody: Rituximab Monoclonal antibody: Rituximab SCT/BMT SCT/BMT

56 In 1994, when I was between my CT appointments, I found another lump in my neck, so I called up the specialist hospital and they told me to come back early for my next scan. At the same time, they did the bone marrow test and the LDH blood test again.

57 When I went back to see the haematologist, he told me that they had found… …swollen lymph nodes in my chest and my armpit, as well as my neck, …which really worried me, although he said the disease had not spread to my bone marrow.

58 Aggressive ( high / intermediate grade): Chemotherapy: mainstay -every 3 weeks, at least 6 cycles yclophosphamide, oxorubicin Hydrochloride, incristine, rednisolonone Chemotherapy: mainstay CHOP -every 3 weeks, at least 6 cycles Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine, Prednisolonone

59 'We talked about what treatment I should have, and the doctor said that, as I had radiotherapy on my neck before, and now other lymph nodes were involved, I couldn't have the same treatment again. However, he offered me chemotherapy instead, and I was given the treatment over the next six months.

60 High risk cases with poor prognostic factors or relapse : High dose chemotherapy combined with autologous BMT / SCT High risk cases with poor prognostic factors or relapse : High dose chemotherapy combined with autologous BMT / SCT Monoclonal antibody Monoclonal antibody With CNS involvement / leukemic relapse : Similar to ALL With CNS involvement / leukemic relapse : Similar to ALL

61 Prognosis Low grade : Median survival –10 yrs Low grade : Median survival –10 yrs High Grade: High Grade: Increasing age, advanced stage, concomitant disease, raised LDH,T- cell phenotype : Poor prognosis Increasing age, advanced stage, concomitant disease, raised LDH,T- cell phenotype : Poor prognosis


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