Hodgkin Lymphoma (HL)
Hallmark Cell
Reed-Sternberg cell — large binucleate "owl-eye" nucleoli; CD15+, CD30+, CD45−. Derived from germinal-centre B-cells.
Subtypes (WHO)
- Nodular Sclerosis — most common (~70 %); collagen bands; young adults; mediastinal mass
- Mixed Cellularity — 20–25 %; EBV-associated; older adults & immunocompromised; more common in GCC/MENA region
- Lymphocyte-Rich — rare; good prognosis
- Lymphocyte-Depleted — rare; HIV-associated; worst prognosis
- Nodular Lymphocyte-Predominant HL (NLPHL) — CD20+, CD15−; "popcorn" cells; indolent
Epidemiology & Risk Factors
Bimodal: 15–35 yrs & >55 yrs
EBV association (mixed cellularity)
Immunodeficiency (HIV, post-transplant)
B Symptoms (prognostic)
- Unexplained fever >38 °C
- Drenching night sweats
- Unexplained weight loss >10 % body weight in 6 months
Pruritus, alcohol-induced pain at nodal sites — not formal B symptoms but common HL features.
Non-Hodgkin Lymphoma (NHL)
Common Subtypes
| Subtype | Key Features |
|---|
| DLBCL | Most common NHL; aggressive; B-cell; CD20+; curable with R-CHOP |
| Follicular | Indolent; grades 1–3; BCL2 rearrangement; t(14;18) |
| Mantle Cell | Aggressive; CD5+; cyclin D1+; t(11;14); ibrutinib era |
| Burkitt | Highly aggressive; c-MYC; EBV-assoc; jaw mass in endemic form; CNS risk |
| Peripheral T-cell | Heterogeneous; poorer prognosis; more prevalent in GCC |
| MALT/Marginal Zone | H. pylori link (gastric); indolent; localised |
GCC Note: T-cell lymphomas and EBV-associated subtypes are proportionally more common in Arab populations compared to Western cohorts.
| Stage | Definition | A / B Modifier |
|---|
| Stage I | Single lymph node region or single extralymphatic organ (IE) | A = No B symptoms
B = Any B symptom
E = direct extralymphatic extension
S = splenic involvement
X = bulky disease (>10 cm or >1/3 mediastinal width) |
| Stage II | Two or more node regions on same side of diaphragm |
| Stage III | Node regions on both sides of diaphragm |
| Stage IV | Diffuse/disseminated extralymphatic involvement (liver, bone marrow, lung parenchyma) |
Lugano modification (2014): CT/PET-based; "limited" (I–II) vs "advanced" (III–IV) disease used in treatment algorithms.
Diagnostic Workup
Biopsy (Gold Standard)
- Excisional lymph node biopsy — preferred; preserves architecture
- Core needle biopsy — acceptable if excision not feasible
- FNA alone — not sufficient for primary diagnosis
Imaging
- PET-CT — staging & response assessment (Deauville 5-point scale)
- CT chest/abdomen/pelvis — where PET not available
- MRI — CNS involvement suspected; spinal cord compression
Laboratory & Marrow
- FBC, LFT, RFT, LDH, uric acid
- LDH — elevated = worse prognosis
- β2-microglobulin — NHL staging/prognosis
- Bone marrow trephine — stage III/IV or cytopenias
- HIV, Hep B/C, EBV serology
- ECHO / MUGA — baseline cardiac function before anthracyclines
International Prognostic Index (IPI) — DLBCL
One point each: Age >60 | LDH > upper normal | ECOG PS ≥2 | Stage III–IV | >1 extranodal site
| Score | Risk Group | 5-yr OS (approx) |
|---|
| 0–1 | Low | ~73% |
| 2 | Low-Intermediate | ~51% |
| 3 | High-Intermediate | ~43% |
| 4–5 | High | ~26% |
HL uses Hasenclever IPI (7 factors): albumin <4, Hb <10.5, male sex, age ≥45, stage IV, WBC ≥15, lymphocyte count <0.6.
ABVD Chemotherapy — Standard HL Regimen
Given every 28 days (day 1 & 15 of each cycle). Early-stage: 2–4 cycles; advanced: 6 cycles.
| Drug | Class | Key Toxicities | Nursing Monitoring |
|---|
| Adriaymcin (Doxorubicin) | Anthracycline | Cardiotoxicity, alopecia, nausea, red urine | Cumulative dose <450 mg/m²; ECHO before & during; vesicant precautions |
| Bleomycin | Glycopeptide antibiotic | Pulmonary fibrosis, skin changes, Raynaud phenomenon | PFTs & 6MWT baseline & each cycle; hold if DLCO <40 %; discontinue if pulmonary symptoms |
| Vinblastine | Vinca alkaloid | Peripheral neuropathy, myelosuppression, constipation | Vesicant — confirm line patency; bowel regimen; neurotoxicity assessment |
| Dacarbazine | Alkylating agent | Severe nausea/vomiting, hepatotoxicity, photosensitivity | Pre-medicate aggressively; sun protection; LFTs |
Before Each Cycle
- FBC — ANC ≥1.0 ×10⁹/L, Plt ≥75 ×10⁹/L required
- LFT, RFT — adjust bleomycin in renal impairment
- Respiratory symptoms review (cough, dyspnoea)
- Pulmonary function: DLCO & SpO₂ (PFTs per institutional protocol)
- ECHO every 3 cycles or if cumulative doxorubicin >300 mg/m²
- Weight, ECOG performance status
- Peripheral neuropathy grading (CTCAE)
Bleomycin Lung Toxicity — Key Points
Risk: cumulative dose >400 units; age >40; prior RT; renal impairment; supplemental O₂ >30 % during surgery (bleomycin sensitises lung to O₂).
- Symptoms: dry cough, progressive dyspnoea, fever, bilateral crackles
- CT findings: bilateral basilar infiltrates, ground-glass opacities
- Management: immediately cease bleomycin; high-dose steroids; respiratory support
- Inform anaesthetics of bleomycin history before ANY surgery
Escalated BEACOPP — Advanced HL
For high-risk advanced-stage HL (IPS ≥3). Higher response rates but significant toxicity.
- Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Oncovin, Procarbazine, Prednisolone
- Higher myelosuppression — G-CSF support mandatory
- Infertility risk significantly higher; fertility preservation before starting
- Secondary AML/MDS risk: 1–3 % at 10 years
- PET after 2 cycles guides escalation or de-escalation
Current GHSG guidelines support PET-adapted approach: start BEACOPP, switch to ABVD if PET-negative at cycle 2.
PET-Adapted Therapy & Response Assessment
Deauville Score (5-point)
| Score | Interpretation |
|---|
| 1–2 | Complete metabolic response (CMR) — negative PET |
| 3 | Minor residual uptake; generally CMR in context |
| 4–5 | Partial/no response — treatment escalation or change |
Interim PET after cycle 2 of ABVD: if Deauville 1–3 → continue; if 4–5 → escalate to BEACOPP or clinical trial.
Radiotherapy in HL
Involved-Site RT (ISRT) — current standard; replaces older involved-field RT. 20–30 Gy to sites of initial disease post-chemotherapy.
- Early-stage HL (I–IIA, non-bulky): ABVD ×2 + ISRT or ABVD ×4 alone (PET-guided)
- Bulky mediastinal disease: chemotherapy + ISRT often required
- Late RT complications: coronary artery disease, valvular disease, breast cancer (mantle field), hypothyroidism, secondary lung cancer
Relapsed/Refractory HL
Salvage Chemotherapy
- DHAP, ICE, GDP, ESHAP — aim to achieve remission pre-SCT
- PET-CR before SCT = significantly better outcomes
Autologous SCT (ASCT)
- Standard of care for first relapse/refractory HL
- GCC centres: KFSH&RC Riyadh, Cleveland Clinic Abu Dhabi, HMC Doha
Brentuximab Vedotin (BV)
- Anti-CD30 antibody-drug conjugate
- Post-ASCT consolidation (AETHERA trial) in high-risk patients
- Key toxicity: peripheral neuropathy (cumulative, monitor with each cycle)
- Also: neutropenia, infusion reactions, progressive multifocal leukoencephalopathy (PML — rare)
Checkpoint Inhibitors
- Nivolumab / Pembrolizumab — PD-1 inhibitors; highly active in R/R HL
- Monitor for immune-related adverse events (irAEs): pneumonitis, colitis, thyroiditis
R-CHOP — Standard DLBCL Treatment
Given every 21 days (R-CHOP-21) or 14 days (R-CHOP-14 with G-CSF). Standard: 6 cycles; limited stage: 3–4 cycles + RT.
| Drug | Route | Key Toxicities | Nursing Points |
|---|
| Rituximab | IV infusion | Infusion reactions (esp. 1st dose), HBV reactivation, PML (rare), tumour lysis syndrome | First dose: start slow (50 mg/hr); pre-medicate paracetamol/antihistamine/steroids; have resuscitation ready |
| Cyclophosphamide | IV | Haemorrhagic cystitis, myelosuppression, SIADH, infertility | Hydrate well; mesna with high doses; monitor UO; strict fluid balance |
| Hydroxydaunorubicin (Doxorubicin) | IV | Cardiotoxicity, alopecia, vesicant | Cumulative dose tracking; ECHO monitoring; vesicant precautions |
| Oncovin (Vincristine) | IV | Peripheral neuropathy, constipation, SIADH | Vesicant; neurotoxicity grading; bowel regimen — lactulose/senna |
| Prednisolone | Oral | Hyperglycaemia, hypertension, mood changes, infection | Glucose monitoring; BP check; advise not to stop abruptly; PCP prophylaxis if immunocompromised |
Day 1 (Clinic Day)
- FBC, U&E, LFT, LDH, uric acid
- ECOG performance status
- Neuropathy assessment (before vincristine)
- Weight — dose recalculation if >10 % change
- Review prior cycle toxicities
- Glucose check (prednisolone patients)
- Blood cultures if febrile
Post-Cycle (Days 7–14)
- Nadir FBC: typically day 7–14
- G-CSF timing: not day 1–3 post-chemo; start day 2–4 (R-CHOP-14) per protocol
- Educate patient: neutropenic fever = medical emergency, go to ED immediately
- Mouth care: chlorhexidine rinses, assess for mucositis
- PICC/Hickman line care: weekly dressing changes, assess for infection
HBV Reactivation Prevention
Screen ALL patients for HBsAg, anti-HBc before rituximab. Prophylactic entecavir/tenofovir for HBsAg+ patients. Monitor HBV DNA in anti-HBc+ patients.
Rituximab Infusion Reactions
First Dose Protocol
- Pre-medicate: paracetamol 1 g PO + diphenhydramine 25–50 mg IV/PO + methylprednisolone 100 mg IV
- Start rate: 50 mg/hr; increase by 50 mg/hr every 30 min if tolerated; max 400 mg/hr
- Subsequent doses: start at 100 mg/hr if prior dose tolerated
Reaction Management (by grade)
- Grade 1–2: reduce rate by 50 %; give antihistamine/paracetamol; resume when symptoms resolve
- Grade 3: stop infusion; IV hydrocortisone; adrenaline if anaphylaxis; may re-challenge at lower rate
- Grade 4: permanently discontinue rituximab
Tumour lysis syndrome risk: bulky disease, high WBC, high LDH — allopurinol/rasburicase pre-treatment; IV fluids; monitor uric acid, K, PO₄, Ca.
Follicular Lymphoma Management
Indolent Disease — Watchful Waiting
- Asymptomatic, low tumour burden (GELF criteria): observation every 3 months
- GELF criteria: any single node >7 cm, ≥3 nodes >3 cm, B symptoms, splenomegaly, effusions, cytopenia, LDH elevated
Treatment Indications
- Bendamustine + Rituximab (BR) — preferred first-line for advanced FL
- R-CHOP — alternative, especially if transformation suspected
- Rituximab maintenance — every 2 months for 2 years post-induction
- Lenalidomide + Rituximab (R²) — relapsed setting
Mantle Cell Lymphoma
- Cyclin D1 overexpression via t(11;14); CD5+, CD20+
- MIPI score guides treatment intensity
- Ibrutinib (BTK inhibitor) — relapsed/refractory and frontline combinations
- Acalabrutinib, zanubrutinib — next-gen BTKi; less atrial fibrillation
- BTKi nursing: monitor for AF, bleeding, hypertension, infections, rash
- Drug interactions: CYP3A4 substrates; avoid strong inhibitors/inducers
- Intensive regimens (young fit): Nordic/R-Hyper-CVAD followed by ASCT
Burkitt Lymphoma
Oncological emergency — doubling time ~24 hrs; urgent treatment initiation required.
- Intensive regimens: CODOX-M/IVAC, DA-EPOCH-R, Hyper-CVAD
- CNS prophylaxis: intrathecal methotrexate/cytarabine with each cycle; lumbar puncture pre-treatment
- Tumour lysis prophylaxis: aggressive IV hydration, allopurinol or rasburicase, continuous monitoring of electrolytes
- High-dose steroids: pre-phase to debulk before chemotherapy if very high tumour burden
CAR-T Cell Therapy — Nursing Implications
Process & Eligibility
- 2nd-line relapsed/refractory DLBCL (axicabtagene, tisagenlecleucel, lisocabtagene)
- Leukapheresis — collect T-cells; manufacturing 2–4 weeks
- Lymphodepleting chemotherapy (fludarabine/cyclophosphamide) before infusion
Cytokine Release Syndrome (CRS)
- Grading: 1 (fever) to 4 (life-threatening organ failure)
- Tocilizumab (IL-6 receptor antagonist) — first-line treatment for grade ≥2
- Corticosteroids for grade ≥3 or tocilizumab-refractory
- ICU monitoring for severe CRS — hypotension, hypoxia
ICANS (Neurotoxicity)
- Immune Effector Cell-Associated Neurotoxicity Syndrome
- Symptoms: confusion, tremor, aphasia, seizures, cerebral oedema
- Daily ICE score (10-point) — assess orientation, naming, commands, writing, attention
- Management: corticosteroids; seizure prophylaxis; avoid tocilizumab (may worsen)
GCC Access: CAR-T limited in GCC 2025. Most patients require medical tourism to Germany, UK, or USA. Saudi Arabia (KFSH&RC) has initiated limited CAR-T programme.
Central Venous Access
PICC Line
- Peripherally inserted central catheter — basilic/brachial vein; tip at SVC/RA junction
- Suitable for ABVD, R-CHOP cycles; vesicant drug delivery
- Weekly dressing change; flush with 10 mL NaCl 0.9 % after each use
- Complications: DVT, infection (CLABSI), occlusion, malposition
Hickman / Long-term CVC
- Tunnelled catheter — preferred for prolonged treatment, SCT, TPN
- Single/double/triple lumen depending on requirements
- Exit site care: inspect for redness, discharge, cuff extrusion
- Heparin lock per local protocol (heparin 100 units/mL or NaCl 0.9 %)
CLABSI prevention: maximal barrier precautions during insertion; chlorhexidine antisepsis; review need daily; aseptic non-touch technique (ANTT) for all access.
Anti-Emesis Protocols
Highly Emetogenic Chemotherapy (HEC) — e.g., BEACOPP
- 5-HT₃ antagonist: ondansetron 8 mg IV/PO day 1 + dexamethasone 12 mg IV day 1–4
- NK-1 antagonist: aprepitant 125 mg day 1, 80 mg days 2–3 (or fosaprepitant)
- Olanzapine 5–10 mg nocte — highly effective for breakthrough & delayed N&V
Moderately Emetogenic (MEC) — ABVD, R-CHOP
- Ondansetron 8 mg IV/PO + dexamethasone 8 mg IV day 1
- Metoclopramide 10 mg TDS for breakthrough
- Prochlorperazine (stemetil) 12.5 mg IM rescue
Non-pharmacological
- Small frequent meals, bland/cold foods, avoid strong smells
- Ginger lozenges, acupressure bands
- Maintain fluid intake; IV fluids if oral route inadequate
Oral Mucositis Management
MASCC/ISOO Grading (WHO scale)
| Grade | Signs/Symptoms |
|---|
| 0 | No mucositis |
| 1 | Soreness/erythema, no ulcers |
| 2 | Erythema, ulcers — can eat solids |
| 3 | Extensive ulcers — liquid diet only |
| 4 | Severe — cannot eat; IV/NG nutrition required |
Prevention & Treatment
- Soft toothbrush twice daily; non-alcohol-based chlorhexidine 0.2 % rinse QID
- Caphosol (calcium phosphate) rinse — reduces severity; 4–10 times daily
- Benzydamine hydrochloride (Difflam) — topical anti-inflammatory rinse
- Palifermin (keratinocyte growth factor) — high-dose conditioning pre-SCT
- Ice chips/cryotherapy during short-infusion chemotherapy (5-FU, melphalan)
- Morphine/opioid analgesia for grade 3–4
- Nutritional support: dietitian review if grade ≥2
- Oral hygiene: avoid alcohol, tobacco, spicy/acidic foods
Neutropenic Fever Management
Definition: single oral temperature ≥38.3 °C or ≥38.0 °C sustained for 1 hour + ANC <0.5 ×10⁹/L (or <1.0 ×10⁹/L and expected to fall below 0.5).
Initial Assessment (within 30 min)
- Full clinical history: last chemo date/regimen; current medications; indwelling lines
- Examination: focus on skin/lines, oral cavity, perianal area, lungs
- FBC, CRP, PCT, LFT, RFT, blood cultures ×2 sets (peripheral + line)
- CXR, urine MC&S, swabs if clinically indicated
- Calculate MASCC score (see tool)
IV Antibiotics — TARGET: within 60 minutes
- High-risk / unstable: Piperacillin-Tazobactam 4.5 g IV 6-hourly OR Meropenem 1 g IV 8-hourly
- Add vancomycin if: line infection suspected, haemodynamically unstable, gram-positive bacteraemia risk
- Antifungal: add if no response at 96 hr (fluconazole/caspofungin)
Low-Risk (MASCC ≥21): Oral Step-Down
- Amoxicillin-clavulanate + ciprofloxacin (or levofloxacin monotherapy)
- Criteria: clinically stable, no co-morbidities, reliable outpatient follow-up, MASCC ≥21
- 24-48 hr IV then oral step-down if clinically improving
Patient & Family Education
- Neutropenic diet: no raw/unwashed produce, undercooked meat/eggs, unpasteurised products
- Hand hygiene — patient, visitors, healthcare workers
- Avoid sick contacts, crowded places during nadir
- Thermometer at home; seek emergency care immediately if T ≥38 °C
- No suppositories or rectal examinations during neutropenia
Transfusion Support
Thresholds (BCSH Guidelines)
- Red cells: Hb <70–80 g/L (symptomatic) or Hb <80 g/L (SCT patients)
- Platelets: <10 ×10⁹/L prophylactic; <20 if febrile/coagulopathic; <50 for procedures
Special Requirements
- Irradiated blood products: mandatory post-ASCT/allogenic SCT; for patients on fludarabine, alemtuzumab, ATG; prevents transfusion-associated GVHD (TA-GvHD)
- CMV-negative blood: CMV-negative recipients pre-SCT if local policy
- Leucodepleted products: standard in most centres (GCC: verify local blood bank policy)
- Group & screen before each cycle; type and crossmatch pre-SCT
Psychosocial & Quality of Life
Hair Loss (Chemotherapy-Induced Alopecia)
- Begins 2–4 weeks after chemotherapy; regrows 3–6 months post-treatment
- Scalp cooling — may reduce alopecia with some regimens (not recommended with haematological malignancies due to scalp disease risk)
- Provide wig vouchers/referral; nursing role in normalising & counselling
Fertility Preservation Counselling
- Discuss before ANY potentially gonadotoxic chemotherapy — ABVD, BEACOPP, CHOP, melphalan
- Men: sperm banking — aim for 2+ samples before treatment
- Women: oocyte/embryo cryopreservation (2–3 weeks delay); ovarian tissue cryopreservation (experimental)
- LHRH agonists (goserelin) — some evidence for ovarian protection during chemotherapy
- GCC-specific: consider religious/cultural beliefs; fatwa permitting fertility preservation in marriage
Late Effects of Treatment
Secondary Malignancies
- Radiation-related: breast cancer (mantle field RT — 5–30 yrs post); lung cancer; thyroid cancer; mesothelioma
- Alkylating agent-related: AML/MDS (BEACOPP, cyclophosphamide) — risk 1–3 % at 10 yrs; onset 2–7 yrs post-treatment
- Annual breast MRI (if chest RT age <30)
- Low-dose CT chest (lung cancer surveillance post-RT)
Cardiovascular Toxicity
- Anthracycline-induced cardiomyopathy: dilated cardiomyopathy; ECHO follow-up at 1, 5, 10 yrs post-treatment
- Radiation-induced heart disease: coronary artery disease (mediastinal RT), pericarditis, valvular disease
- Risk modification: statin, ACE-I, beta-blocker if EF falls; aggressive CV risk factor management
- Cardiac MRI for borderline ECHO findings
Endocrine & Other Late Effects
- Hypothyroidism: neck RT; annual TSH monitoring for life
- Infertility/Premature Ovarian Insufficiency: alkylating agents; FSH/LH/AMH monitoring
- Pulmonary fibrosis: bleomycin + lung RT — long-term PFT follow-up
- Peripheral neuropathy: vincristine, brentuximab — may persist >1 year
- Avascular necrosis: long-term steroid use
- Osteoporosis: premature menopause, steroid use — DEXA scan; bisphosphonates
PET Remission Monitoring Schedule
Post-Treatment Surveillance (HL & DLBCL)
| Time Point | Assessment |
|---|
| End of treatment | PET-CT (Deauville scoring) |
| Every 3–6 months (yr 1–2) | Clinical exam, FBC, LDH, CRP |
| Every 6 months (yr 3–5) | Clinical exam, bloods; CT only if clinically indicated |
| Annually (>5 yrs) | Late effects monitoring (see left) |
Routine surveillance PET scans not recommended beyond 2 yrs — low yield, radiation exposure, false positives (anxiety).
Follicular Lymphoma Surveillance
- Watchful waiting: FBC/LDH/clinical exam every 3 months for 2 yrs, then 6-monthly
- Post-treatment: CT at 6 weeks + 12 months; then clinical surveillance
- Transformation risk: ~3 %/year; biopsy new bulky/rapidly growing nodes; elevated LDH
Asplenic/hyposplenic patients at high risk of Overwhelming Post-Splenectomy Infection (OPSI) — most commonly Streptococcus pneumoniae, Haemophilus influenzae type b, Neisseria meningitidis. Mortality 50–70 % once established.
Vaccinations (ideally ≥2 weeks before splenectomy or ≥2 weeks post-chemotherapy)
| Vaccine | Schedule | Booster |
|---|
| Pneumococcal conjugate (PCV13/15) | Single dose | Followed by PPSV23 at 8 weeks; then PPSV23 every 5 yrs |
| Meningococcal ACWY | Single dose | Every 5 yrs |
| Meningococcal B (MenB) | 2 doses, 1 month apart | Every 2–3 yrs |
| Haemophilus influenzae b (Hib) | Single dose | Every 5 yrs if ongoing risk |
| Annual influenza | Every October/November | Annually |
Antibiotic Prophylaxis
- Penicillin V 250–500 mg BD for life (or amoxicillin)
- Azithromycin if penicillin allergic
- Patient must carry an emergency antibiotic supply (amoxicillin 3 g stat or co-amoxiclav) and know to take it if unable to see a doctor promptly
- Medical alert bracelet/card — mandatory; inform all healthcare providers
GCC nurses: splenectomy may occur due to lymphoma staging (historical) or disease complications. Ensure vaccination documentation and lifelong prophylaxis education in discharge planning.
Psychological Impact & Survivorship Support
Common Psychological Issues
- Anxiety: especially at diagnosis, during treatment, at follow-up appointments ("scanxiety")
- Depression: incidence 20–30 % in lymphoma patients; screen with PHQ-9/HADS
- Fear of recurrence: may intensify after treatment ends (loss of structured care)
- PTSD: particularly post-ICU/severe illness (CAR-T CRS, SCT complications)
- Body image: alopecia, weight changes, line scars, lymphoedema
Nursing Interventions
- Regular psychological screening (HADS/distress thermometer at each visit)
- Refer to oncology psychologist / social worker early
- Peer support groups — particularly valued in Arabic-speaking communities
- Mindfulness-based stress reduction (MBSR) — evidence-based for cancer survivors
- Clear communication: survivorship care plan at end of treatment
Return to Work & Daily Life
- Graduated return to work — typically 4–8 weeks post last chemotherapy
- Fatigue (CTCAE) — most common symptom post-treatment; exercise programme (supervised aerobic)
- Cognitive changes ("chemo brain") — memory, concentration; neuropsychological referral if severe
- Sexual health: discuss side effects of treatment on libido, erectile function, vaginal dryness
- Driving: advise when safe to drive (no sedating medications, adequate cognition)