1-Work up for newly diagnosed NHL

Pathology specimen is recommended with the proper IHC.

strong recommendation, high quality level of evidence (ICC report) ⁽⁶⁾

We recommend whole body FDG- PET CT if available otherwise contrast enhanced CT neck, chest, abdomen and pelvis is recommended.

strong recommendation, high quality level of evidence (COG report, retrospective analysis, retrospective analysis,) ^{(7)(8)(9)(10)}

Bilateral bone marrow aspiration and biopsy is recommended as well as CSF examination.

strong recommendation, high quality level of evidence (prospective trial, retrospective review) ^(11)(12)

2-Treatment of clinical group A

Two 21-day cycles COPAD are recommended

strong recommendation, high quality level of evidence (prospective trials, multinational cooperative trial) ^(13)(14)(15)

Response assessment is recommended to include imaging of the primary site.

strong recommendation, high quality level of evidence (COG report, retrospective analysis) ⁽⁷⁾⁽⁹⁾

3-Treatment of clinical group B

Multiagent chemotherapy is recommended starting with pre phase COP Followed by response assessment post COP. Then administer 2 induction courses COPADM₃ and two consolidation courses CYM.

strong recommendation, high quality level of evidence (prospective trial, prospective randomised trial) ^(11)(14)

Contrast enhanced CT neck, chest, abdomen and pelvis is recommended for response assessment after COP and FDG- PET/CT is recommended for assessment after CYM I.

strong recommendation, high quality level of evidence (prospective trial, prospective randomised trial) ^(10)(12)

Response assessment after CYM I:

· If in CR, then continuation of CYM II is recommended.

· If not in CR, biopsy is recommended. If biopsy is not feasible then continue as group B if PET/CT is negative. Upgrade to group C if biopsy is viable or PET/CT is positive.

strong recommendation, high quality level of evidence (prospective trial, prospective randomised trial) ^(11)(14)

Rituximab addition to chemotherapy is recommended in all high-risk group B

strong recommendation, high quality level of evidence (international prospective randomised trial) ⁽¹⁵⁾

4-Treatment of clinical group C

Multiagent chemotherapy should be initiated with pre phase R-COP, followed by 2 induction courses (R-COPADM₈), 2 consolidation courses (R-CYVE) and 2 maintenance courses (Sequences 1 and 2).

strong recommendation, high quality level of evidence (prospective trial, randomised trial) ^(12)(16)

Rituximab addition to chemotherapy is recommended for all group C patients

strong recommendation, high quality level of evidence (COG report) ⁽¹⁷⁾

For Group C CNS disease: We recommend a total of 3 intrathecals in pre phase COP and high dose methotrexate after CYVE I

strong recommendation, high quality level of evidence (Randomised trial, international randomised trial) ^(16)(18)

5-End of treatment evaluation

End of treatment evaluation should be done and if in CR then follow up is recommended

If not in CR, repeat biopsy from suspicious lesions, and if relapse is confirmed, start relapse protocol.

strong recommendation, high quality level of evidence (COG report, prospective randomised trial) ^(7)(12)

6-Treatment of relapse or refractory disease

Combination chemotherapy is recommended with regimen:

(R-ICE) Rituximab, ifosfamide, carboplatin, etoposide and intrathecal chemotherapy

strong recommendation, high quality level of evidence (COG report, retrospective analysis of multicentre trial) ^(19)(20)

7- Surveillance (follow up after end of treatment)

Routine scans are not recommended unless clinically suspicious. Monthly clinical examination is recommended for the first 3 years then annually.

Conditional recommendation, moderate quality level of evidence (retrospective analysis) ⁽²¹⁾

Clinical indicators for monitoring:

· Contrast enhanced CT neck, chest, abdomen and pelvis initially.

· Confirmed Pathology.

· CSF analysis initially.

· Bone marrow aspiration and biopsy.

· Evaluation by imaging of primary site after COP in groups B and C.

· Evaluation after CYM I by imaging of primary site.

Update of this guideline

This guideline will be updated whenever there is new evidence.