Recent guidelines by WHO, ESMO

1. CASE PRESENTATION BY
DR LAJPAT RATHORE

2. Name Khuda Dad
 Age - 13 years
 Sex – Male
 Admitted through OPD
 Addres – Awaran Balochistan

3. Presenting Complain
 Fever for last1 year
 Weight loss for last 6 months

4. History of Presenting Illness
 According to patient he was in usual state of health 1 year
back then he developed low grade fever, gradual in onset, not
associated with rigors or chills, fever pattern was intermittent
or relapsing and relieved by antipyretics.
 Patient is also complaining of weight loss which is 10 kg in
past 6 months associated with poor appetite.

5. Drug history
 He took antipyretics for fever.
 He also took multivitamins prescribed by general practioner

6. Personal History
 Sleep - Adequate
 Appetite - decreased
 Bowel Habits - normal
 Micturation - normal
 Addiction – no hx of addicton

7. Family History
 There is no family history of hypertension, diabetes mellitus,
ischemic heart disease, asthma, arthritis or tuberculosis.

8. Socioeconomic history
 Satisfactory

9. Systemic Review
 General  decreased appetite, significant weight loss and
decreased energy.
 Rest of the systems are unremarkable

10. General Physical Examination
 Young boy thin and lean sitting confortably on bed.
 Vitals
 Bp 100/60mmHg
 Pulse 120 beats per minute
 Temperature 1010F
 R/R 18 breaths per minute
 Anemia +ve severely
 Jaundice negative
 Clubbing –ve
 Edema –ve

11. General Physical Examination
 Lymph Nodes
 Anterior and posterior cervical lymph nodes are palpable, multiple,
largest one was >2cm, non tender, discrete and rubbery in
consistency.
 Lymph nodes of axillary, inguinal regions are nonpalpable.

12. Systemic Examination
 Respiratory System
Normal vesicular breathing, no added sounds.
 Abdomen
Abdomen is soft and no tender, no visceromegaly
 Cardiovascular system
S1+ S2 + 0
 Central Nervous System
Higher mental function, all cranial nerves, motor and sensory sytems
intact.

13. Differential Diagnosis
 What you think?

14. Differential Diagnosis
 Viral infection like infectious mononucleosis
 Brucelossis
 Tuberculosis
 Lymphoma
 Leukemia

15. Investigation

16. CBC
 CBC
Hb  8.7g%
PCV  30
MCHC  32
RBC  3 million
Platelet  180,000
 CBC
 TLC 10700
 Neutrophil  72%
 Lymphocytes  24%
 Eosinophil  2%
 Monocytes  2%

Peripheral Film
 Hypochromic anisocytosis / poiklocytosis / rolux formation ++

17. ESR
ESR  120 in first hour

18. LFT and UCE
 LFT
Total bilirubin  0.7
SGPT  18
Alkaline phosphatase 
865
 UCE
 Urea  22
 Creatinine  0.7
 Sodium  139
 Potassium  4.7
 Chloride  109

19. Viral Markers
Hepatitis B surface antigen  Non reactive
Anti HCV antibodies  Non reactive

20. Chest X ray
 Widening of mediastinum noted onto right side
with lobulated margins
 Normal heart size
 Both cardio phrenic angles are clear.
 Bony cage is intact.

21. US Chest and abdomen
 Chest ultrasound reveals no free fluid and there
was patch in right mediastinum.
 Hepatomegaly with prominent portal radicals
 Rest of the ultrasound unremarkable
 Sonologist advised CT Chest.

22. CT scan Chest
Massive anterior and middle mediastinal lymphadenopathy with
mild supraclavicular lymphadenopathy showing enlarged lymph
nodes and confluent masses causing compression effect over
the mediastinal vessels and trachea

23. At this stage all workup does not
lead to final diagnosis, so we
planned for excisional biopsy

24. EXCISONAL BIOPSY OF CERVICAL LYMPH NODE
 HISTOPATHOLOGY
Section examined from cervical lymph node with complete
effacement of corticomedullary architecture replaced by sheets of
lymphoid cells in various grades of maturation along with scattered
large atypical mononuclear cells with large nuclei, prominent red
nucleoli and abundant cytoplasm. Large binucleated cell are also
seen at places. Plasma cells and eosinophils are also seen.
All these findings are suggestive of Lymphoproliferative disorder
with Hodgkin’s Lymphoma (mixed cellularity)

25. Final Diagnosis
?

26. Hodgkin's Lymphoma
Mixed cellularity type

27. MANAGEMENT OF HODGKIN’S LYMPHOMA

28. Etiology
 ? Infection – EBV
 ? Environmental factors

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

30. Clinical Staging
 History/ Physical examination
 CT scan neck, thorax, abdomen
 18FDG-PET scan
 Bone marrow biopsy

31. Ann Arbor staging
 Stage I : Involvement of single LN region (I) or extra lymphatic
site (IAE )
 Stage II :Two or more LN regions involved (II) or an extra
lymphatic site and lymph node regions on the same side of
diaphragm
 Stage III : Involvement of lymph node regions on both sides of
diaphragm, with (IIIE) or without (III) localized extra lymphatic
involvement or involvement of the spleen (IIS) or both (IISE)
 Stage IV : Involvement outside LN areas (Liver, bone marrow)
A : Absence of ‘B’ symptoms
B : B symptoms present (fever, night sweats, weight loss)

32. Ann Arbor staging

33. Treatment
 Chemotherapy is mainstay of treatment for Hodgkin's Lymphoma
 ABVD: (standard first line regimen )
 Adriamycin
 Bleomycin
 Vinblastine
 Dacarbazine
 StanfordV or Escalated BEACOPP
 Bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine,
procarbazine, prednisone)
 Improves response rate and reduce the need for consolidative radiotherapy.
 Lack a definitive overall survival advantage.

34. Treatment
 Low risk patients
Stage I or II disease without bulky LAD or evidence of systemic inflammation
These patients treated with short course chemotherapy with involved field
radiotherapy or full course chemotherapy alone
 High risk patients
Stage III or IV disease or with stage II and a large mediastinal or other bulky
mass.
These patients treated with full course of ABVD for six cycles.

35. Pulmonary Toxicity
 It can occur following chemotherapy (bleomycin) or radiation
and should be treated aggressively since it can lead to
permanent fibrosis or death.

36. Classic Hodgkins Lymphoma relapses
 They are treatable with high dose chemotherapy and
autologous hematopoietic stem cell transplantation.
 This offers 35-50% chance of cure when disease is
chemotherapy responsive.
 Antibody drug conjugate bretuxinab vedotin has shown
impressive activity in patients relapsing after autologous stem
cell transplantation (ORR 75%, CR 34%) and it is approved by
US FDA.
 It is now being studied in frontline therapy, replacing
bleomycin in ABVD.

37. Brentuximab vedotin
 Brentuximab vedotin is an antibody-drug conjugate (ADC)
used to treat relapsed or refractory Hodgkin lymphoma (HL)
and systemic anaplastic large cell lymphoma (ALCL). It
selectively targets tumor cells expressing the CD30 antigen, a
defining marker of Hodgkin lymphoma and ALCL (a type ofT
cell non-Hodgkin lymphoma).

38. Prognosis
 All patients should be treated with curative intent.
 Prognosis in advanced disease in influenced by seven features:
stage, age, gender, hemoglobin, albumin, WBC and lymphocyte
count.
 The cure rate is 75% if zero or two risk factors are present and
55% when 3 or more risk factors.
 Patients with stage IA or IIA disease is excellent with 10 year
survival rates in excess of 90%.
 Patietns with advanced disease (stage III or IV) have 10 year
survival rates of 50-60%.

39.  Poorer results are seen in patients with who are older, those
who have bulky disease, those with lymphocyte depleted or
mixed cellularity on histologic examination
 Non classic Hodgkin's lymphoma (nodular lymphocyte
predominant) is highly curable with radiotherapy alone for
early stage disease, however for high stage disease it is
characterized by long survival with repetitive relapses after
chemotherapy.
Prognosis

40. Treatment Results ?

41. Treatment of Hodgkin lymphoma
summary Stage I/II
 Excellent results
 Future
 maintain results
 reduce (late) toxicity
- reduce/ omit Radiotherapy?
- reduce Chemotherapy
 PET guided treatment (interim; postTx)?

42. Treatment of Hodgkin lymphoma
summary Stage III/IV
 Results moderate/good (cf DLBCL!)
 Future
 Improve results without increasing (late) toxicity
- more intensive chemotherapy?
 PET guided treatment
 Interim: escalate if positive?
 PostTx: if positive radiotherapy/ HDT+ AuSCT?

43. Treatment for relapsed
Hodgkin lymphoma
 15-30% of all HL patients will relapse and require second-line treatment
 High-dose chemotherapy and autologous stem cell transplantation:
- superior over conventional chemotherapy
(Linch et al., Lancet 1993, Schmitz et al., Lancet 2002)
- remains the standard of care for relapsed HL
(except very late relapse?)

44. High Dose CT + AutoSCT
in relapsed HL
PFS @ 5 yrs
%
OS @ 5yrs
%
Relapse 45-60 50-65
Primary resistant 20-30 20-30

45. Successfull treatment of HL
Long term survival
Late effects of treatment
The reverse of the success

46. m Hodgkin: Late Toxicity of Treatment
 Excess mortality
 secondary malignancies
 cardiac disease
 Excess morbidity / decreased Q.O.L
 cardiac disease
 pulmonary disease
 infertility
 fatigue

47. m.Hodgkin : Late Toxicity of Treatment
Secondary Malignancies
Relative
Risk
Absolute
Excess Risk
per 10,000
pat. per yr
Absolute
Excess Risk
in 10-yr
survivors
AML 70.8 15.5 9.0
NHL 18.6 10.7 27.8
Solid
tumors
2.4 29.3 74.4
-- lung 4.2 13.5 33.8
-- breast 2.5 11.3 39.5
all 3.5 56.2 111.7

48. m.Hodgkin : Late Toxicity of Treatment
Cardiac disease
 coronary insufficiency
myocardial infarction RR 1.9 - 3.7
 acute cardiac arrest RR 1.9 - 3.1
 pericarditis
 cardiomyopathy RR 1.4 - 5.1
 valvular abnormalities

49. m.Hodgkin : Late Toxicity of Treatment
Risk Factors for Cardiac Disease
 Mediastinal RT dose > 30 Gy
 Orthovolt RT (before 1967)
 Adriamycine containing CT
 Age at RT < 20 yr
 Hypertension

50. Adverse Effects of Chemotherapy
 BLEOMYCIN
 Acute  hypersenstivity, fever
 Delayed  skin reaction (rash, hyperpigmentationof skin, stria) mucositis,
pneumonitis (fibrosis)
 ADRIAMYCIN (DOXORUBICIN)
 Acute  nausea, vomiting, diarrhea, red orange discoloration of urine,
 Delayed  myelosupression, alopecia, mucositis, hand foot syndrome and
cardio toxicity (dose related)
 Dexrazoxane prevent cardiomyopathy secondary to doxorubicin,
anthracycline-induced injection extravasation.

51. Adverse Effects of Chemotherapy
 Vinblastine
 Acute  constipation
 Delayed  myelosupression, alopecia, bone pain and malaise
 Dacarbazine
 Acute  Nausea, vomiting, photosensitivity, fever
 Delayed  myelosupression, anorexia, hypotension and flu like syndorme.

52. Adverse Effects of Chemotherapy
 Etoposide
 Acute  nausea, vomiting, diarrhea, hypersensitivity, fever, hypotension
 Delayed  myelosupression, alopecia, fatigue
 Cyclophosphamide
 Acute  nausea, vomiting
 Delayed  myelosupression, alopecia, hemorrahgic cystitis, cardiotoxixicity (high dose)
 Mesna is given to prevent cyclophosphamide induced hemorrhagic cystitis.

53. Adverse Effects of Chemotherapy
 Vincristine
 Acute  constipation, nausea
 Delayed  peripheral neuropathy alopecia
 Procarbazine
 Acute  nausea, vomiting
 Delayed  myelosupression, disulfuram like reaction, flu like syndrome