HODGKIN LYMPHOMA IN CHILDREN

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HODGKIN LYMPHOMA IN CHILDREN

• Dr.M.Shamvil Ashraf
• Children Cancer Hospital,
• Karachi.

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Hodgkin Lymphoma

• One of the most curable cancer in children
• There are different effective treatment
  approaches
• Can be cured with limited resources

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Epidemiology

• Developed Countries
• 5 - 6 of childhood cancers
• MaleFemale 3-41 in lt10y
• MaleFemale 1.31 in gt10y
• Bimodal age peak- adolescent/young adult, 50yo
• Uncommon in lt10 yrs

• Karachi Data
• 10 of childhood cancers
• MaleFemale 4.71 in lt10y
• MaleFemale 1.71 in gt10y
• gt 5 years 24
• gt10years 62

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Biology

• Inflammatory milieu with rare multinucleated
  giant cells (Reed-Sternberg cells) or large
  mononuclear cell variants (Hodgkins 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

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RS cells
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Lacunar Cells
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Cellular Classification

• Classical HL (CD15, CD30 , B cell markers )
• nodular sclerosis (50-60)
• mixed-cellularity (20-30)
• lymphocyte rich (lt5)
• lymphocyte depleted (5-15)
• Nodular Lymphocyte Predominant HL (5) (CD15 -,
  CD30 /-, B cell markers )

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Pathological Subtypes Karachi Data
13 (16.2)
2 (2.5)
21 (26)
44 (55)
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Clinical Presentation

• Painless adenopathy (80)
• B symptoms (25-30)
• fever gt380C x 3 days
• wt loss gt10 of body wt. over 6 mo
• drenching night sweats
• Bulky disease (20)
• med mass gt1/3 of internal thoracic diameter
• node/nodal aggregate gt6 cm

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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

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Hodgkin vs TB

• Most common differential especially if limited to
  cervical
• Often put on ATT without definitive diagnosis
• Biopsy is essential

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Diagnosis

• Excision Biopsy of Node
• Needle Biopsy of mass if excision not possible
• FNAC is not recommended in children

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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)

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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
  ES)
• 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.

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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

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Therapy History

• XRT alone cured early stage disease
• 1960s- MOPP
• 1970s- ABVD
• Combined modality therapy (CMT)? Chemotherapy and
  radiation

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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

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Combination Chemotherapy Regimens Commonly Used
for Children and Young Adults with Hodgkin
Lymphoma
ABVD doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine
ABVE doxorubicin (Adriamycin), bleomycin, vincristine, etoposide
VAMP vincristine, doxorubicin (Adriamycin), methotrexate, prednisone
OPPA /- COPP vincristine, prednisone, procarbazine, doxorubicin, cyclophosphamide, vincristine (Oncovin), prednisone, procarbazine
COPP/ABV cyclophosphamide, vincristine (Oncovin), prednisone, procarbazine, doxorubicin (Adriamycin), bleomycin, vinblastine
BEACOPP bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), prednisone, procarbazine
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Hodgkins Therapy in 90s

• 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

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Determining Risk Assignment
I
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Chemotherapy Options
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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.

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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)

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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

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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

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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

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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

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Response Assessment Criteria

• CR was taken as complete resolution of all
  measurable disease, clinically and radiologically
• gt80 response was taken as good response
• 60 to 80 was taken as partial response
• lt60 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

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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

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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

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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

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Progressive/Relapsed Ds

• Prognostic factors
• progressive ds or relapse at lt1y from end of
  treatment
• B symptoms
• extranodal ds
• response to salvage therapy

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Chemotherapy Options

• Salvage therapies (with harvest)?
• ICE, EPIC,mini-BEAM, DHAP, ASHAP,
  bortezomib/ifos/vinorelbine (AHOD 0521)?, GDP
  (PMH)
• Autologous transplant
• conditioning CBV, BEAM, VP16/melphalan
• BEAM plus immunomodulation (AHOD 0121)?- closed

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Refractory Disease

• Gemcitabine/Vinorelbine AHOD 0321- closed
• eligibility gt/ 2 prior regimens
• beware non-cardiogenic pulmonary edema
• may require 4-6 cycles to see response
• Vinblastine, lomustine, VP16
• New agents/targeted therapies

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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

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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