2. Hodgkin Lymphoma
One of the most curable cancer in children
There are different effective treatment
approaches
Can be cured with limited resources
3. Epidemiology
Developed Countries
5 - 6% of childhood cancers
Male:Female 3-4:1 in <10y
Male:Female 1.3:1 in >10y
Bimodal age peak-
adolescent/young adult,
50yo
Uncommon in <10 yrs
Karachi Data
10% of childhood cancers
Male:Female 4.7:1 in <10y
Male:Female 1.7:1 in >10y
> 5 years 24%
>10years 62%
4. Biology
Inflammatory milieu with rare multinucleated
giant cells (Reed-Sternberg cells) or large
mononuclear cell variants (Hodgkin’s or
lacunar cells)
R-S cell appears to arise from preapoptotic
germinal center B cells (no Ig production),
although rarely may arise from T cells
9. Clinical Presentation
Painless adenopathy (80%)
B symptoms (25-30%)
fever >380C x 3 days
wt loss >10% of body wt. over 6 mo
drenching night sweats
Bulky disease (20%)
med mass >1/3 of internal thoracic diameter
node/nodal aggregate >6 cm
10. Clinical Presentation
15% to 20% of patients will have
noncontiguous extranodal involvement
The most common sites of extranodal
involvement are the lung, liver, bones, and
bone marrow
11. Hodgkin vs TB
Most common differential especially if limited
to cervical
Often put on ATT without definitive diagnosis
Biopsy is essential
12. Diagnosis
Excision Biopsy of Node
Needle Biopsy of mass if excision not possible
FNAC is not recommended in children
13. Staging
Ann Arbor staging system I-IV
“A” vs “B”
“E”- extralymphatic disease resulting from
direct extension of involved LN region
“S”- splenic disease
ideally want pathologic confirmation of
noncontiguous extralymphatic involvement
(Stage IV disease)
14. Ann Arbor Staging
Stage I: Involvement of single lymph node region (I) or localized involvement of a single
extralymphatic organ or site (IE)
Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm
(II) or localized involvement of a single extralymphatic organ or site and its regional lymph
node(s) with involvement of one or more lymph regions on the same side of the diaphragm
(IIE)
Stage III: Involvement of lymph node regions on both sides of the diaphragm (III), which
may also be accompanied by localized involvement of an extralymphatic organ or site (IIIE),
by involvement of the spleen (IIS), or both (III E+S)
Stage IV: Disseminated (multifocal) involvement of one or more extralymphatic organs or
tissues, with or without associated lymph node involvement, or isolated extralymphatic organ
involvement with distant (non-regional) nodal involvement.
15.
16. Staging Workup
Imaging
CXR
U/Sound
CT scan of neck, chest, abdomen and pelvis
Gallium
PET Scan
Other Tests
Bone marrow aspirate and trephine only in
Patients with stage II B or more
Bone scan only in stage III or more
Blood tests
CBC
LDH
Urea, Cr, electrolytes, Ca, Mg, LFTs
Hepatitis screening
17. Therapy: History
XRT alone cured early stage disease
1960s- MOPP
1970s- ABVD
Combined modality therapy (CMT)
Chemotherapy and radiation
18. Therapy History
Good results were obtained but at the cost of
severe late toxicities
XRT ; profound musculoskeletal growth
retardation and increase the risk for
cardiovascular disease and secondary solid
malignancies in children
Chemotherapy induced gonadal
injury,cardiovascular disease and SMN
20. Hodgkins Therapy in 90`s
Prognostic factors and risk grouping concept
introduced
Radiation dose and field were reduced
Involved Field Radiotherapy introduced
Chemotherapy regimen were manipulated
to reduce cumulative dose and avoid long term
toxicities
23. Current Approaches
Current approaches use chemotherapy with or
without LD-IFRT
An exception to this general approach is selected
patients with stage I, completely resected, nodular
lymphocyte-predominant Hodgkin lymphoma, whose
initial treatment may be surgery alone.
The number of cycles and intensity of chemotherapy
may be determined by the rapidity and degree of
response, as is the radiation dose and volume.
24. Approach for Developing Countries
Chemotherapy Alone
If radiotherapy is not available
Pediatric radiotherapy service is not developed
Good result (up to 80% survival) can be obtained
as shown by Indian Experience
(Arya et al)
25. Approach for Developing Countries
Chemotherapy with Radiotherapy only for
bulky residual disease
Excellent result can be achieved with this
approach as shown by our experience at
Children Cancer Hospital
26. CCH Data
Retrospective study
From Aug 2000 - 2007All the patients with
histopathological diagnosis of Hodgkin
Lymphoma, up to 20 years of age were
included
Mean age: 9.9 yrs
Pts. included in the study – 80
27. Treatment Strategy At CCH
Chemotherapy used was alternating courses of
ABVD (adriamycin, bleomycin, vincristine and
dacarbazine)
COPDAC (cyclophophamide, vincristine,
prednisolone and dacarbazine)
Radiotherapy was reserved only for the pts.
with significant residual disease at the end of
chemotherapy
28. Response Assessment
CT scan of all the sites positive on pre
treatment scan was repeated after 2 cycles
Bone marrow or bone scan was repeated only
if it was positive initially
For good responder CT was repeated after 6
cycles
PET scan could not be performed because of
non-availability
29. Response Assessment Criteria
CR was taken as complete resolution of all
measurable disease, clinically and radiologically
>80% response was taken as good response
60 to 80% was taken as partial response
<60% was taken as poor response or stable disease
Any increase in the size of an existing lesion or
appearance of any new lesion during treatment was
taken as progressive disease
30. Response Adapted Therapy
Low risk patients with CR after 2 courses
received 4 courses
All other pts were given 6 – 8 courses
depending upon the response (CR + 2 courses)
11(13.7%) pts received 4 courses
Majority of pts 56 (70%) received 6 courses
31. Radiation Therapy
Radiation therapy was reserved only for the pts
with residual disease at the end of chemo
only 8 (10%) needed radiation
Stage II A – 1 pt
Stage II B – 1 pt
Stage III B – 3 pts
Stage III BS – 1 pt
Stage IV – 2 pts
32. Results
74 (92%) pts achieved first remission (CR)
after 2 courses of chemotherapy
Only one pt. died during chemotherapy due to
meningitis
One pt. relapsed on treatment and was
switched to second line treatment
4 (5%) pts relapsed 2 – 12 months after
completion of chemotherapy
3 yrs OS 98% and EFS 92%
33.
34. Progressive/Relapsed Ds
• Prognostic factors:
– progressive ds or relapse at <1y from end of treatment
– B symptoms
– extranodal ds
– response to salvage therapy
36. Refractory Disease
• Gemcitabine/Vinorelbine AHOD 0321- closed
– eligibility: >/= 2 prior regimens
– beware non-cardiogenic pulmonary edema
– may require 4-6 cycles to see response
• Vinblastine, lomustine, VP16
• New agents/targeted therapies
37. Late Effects
Cardiotoxicity and Musculoskeletal problems
are now rare
Endocrine
Thyroid ; Hypothyroidism
Fertility;
Increased risk of ovarian failure in women
Oligospermia and sterility in men
Second Malignant Neoplasm
38. Conclusion
Chemotherapy alone in majority of patients with
Hodgkin Lymphoma can yield excellent outcome
Most of Hodgkin Disease pts can be managed without
the use of radiotherapy, thereby minimizing the
adversity associated with radiation, specially in young
children
Hodgkin Lymphoma can be cured within limited
resources
Monitoring for late effects is important
