bubble_chart Overview

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of malignant proliferative tumors of lymphoid tissue. In children, it mostly presents as diffuse sexually transmitted disease changes, with rapid disease progression, but treatment outcomes have significantly improved in recent years.

bubble_chart Type

There are numerous pathological classification methods. Pediatric NHL differs from adults, mostly presenting as diffuse high-grade malignancies, and the following classification is commonly used:

1. **Lymphoblastic type**: The immunophenotype is mostly mature T-cell type, with a minority being early pre-B-cell type. Common genetic abnormalities include t(11;14), t(1;14), t(1;19), t(10;14), etc., and the resulting gene rearrangements such as TCR.
2. **Small non-cleaved cell type (Burkitt lymphoma)**: The immunophenotype is exclusively B-cell type. Common genetic abnormalities include t(8;14), t(8;22), t(2;8), etc., and the corresponding gene rearrangements such as 19μ/C-myc, Igλ/C-myc, Igκ/C-myc. This type is further divided into African-type and non-African-type Burkitt lymphoma.
3. **Large cell type**: This is a heterogeneous group of NHL, mostly originating from B-cells, with a minority from T-cells and true histiocytes. Approximately 30% of cases are anaplastic large cell lymphoma (ALCL), expressing Ki-1+ (CD30+) and T-cell markers, rarely B-cell markers or null phenotype. ALCL often exhibits the chromosomal change t(2;5)(p23;q35) and the corresponding NPM/ALK fusion gene, which some consider a characteristic abnormality of ALCL, seen in about 50% of ALCL cases.

**Staging diagnosis** is largely similar to HD. However, any primary intrathoracic tumor, extensive primary abdominal follicular tumor, or any paravertebral or epidural tumor is classified as stage III, while completely resectable primary gastrointestinal tumors (e.g., ileocecal region) are classified as stage II.

bubble_chart Clinical Manifestations

1. Systemic symptoms include fever accompanied by weight loss, pallor, and lack of strength.
2. Characteristics of the primary follicular tumor: Approximately one-third to one-half of cases are located in abdominal lymphatic tissue, which may present with abdominal pain, nausea, vomiting, and progressively enlarging abdominal masses. About one-third of cases are located in the mediastinum, which may lead to pleural effusion or superior vena cava syndrome, with a higher likelihood of bone marrow and central nervous system involvement. Around 20–30% of cases present with painless enlargement of peripheral lymph nodes. In children, lesions in the Waldeyer's ring (tonsils, nasopharynx, soft palate, base of the tongue) are more common. A minority of cases have primary lesions confined to extranodal organs, with or without regional lymph node infiltration, most frequently in the gastrointestinal tract, but also seen in the skin, liver, spleen, heart, kidneys, bones, nervous system, etc.
3. NHL tends to metastasize to distant lymph nodes or extranodal organs, and about 30–40% of pediatric NHL cases can progress to lymphoblastic leukemia.
4. Burkitt's lymphoma (African type) is an undifferentiated lymphoma that often invades the face and jaw, presenting with gum swelling, tooth loss, nasal obstruction, and proptosis. The disease progresses rapidly but responds well to chemotherapy, allowing for long-term remission.

bubble_chart Auxiliary Examination

Laboratory Examination

1. Blood tests may show normal results or anemia. The differential white blood cell count may reveal eosinophilia and tumor cells, while platelets may be normal or decreased.
2. Bone marrow examination is generally normal in the early stages. In advanced stages, tumor cells may be observed, and cases with tumor cells >25% are referred to as fleshy tumor leukemia.
3. Elevated serum lactate dehydrogenase and serum IL-2 receptor levels are important poor prognostic factors.
4. Routine cerebrospinal fluid examination before treatment is necessary to determine central nervous system involvement.
5. Immunological tests using a series of monoclonal antibodies can detect surface antigens on tumor cells, helping to identify their origin.
6. Genetic testing of tumor cells can reveal chromosomal karyotype changes, gene rearrangements, deletions, or mutations.

Imaging diagnosis: B-ultrasound for detecting abdominal lesions, and X-ray or CT scans for examining the thoracic cavity and gastrointestinal tract can provide crucial evidence for diagnosis and staging.

Biopsy of tumor tissue and lymph node sections for pathological morphology and immunological examination serves as the primary basis for definitive diagnosis.

bubble_chart Treatment Measures

NHL at all stages is primarily treated with combined chemotherapy, supplemented by radiotherapy when necessary. Surgical treatment is suitable for gastrointestinal B-cell lymphoma presenting with acute abdomen. Different chemotherapy regimens are employed for T-cell and B-cell NHL. For T-cell NHL, a regimen similar to that for heat stranguria leukemia is used, with a long treatment course, achieving long-term survival rates of 80–90% for stages I and II, and 65–80% for stages III and IV. For B-cell NHL, current recommendations emphasize repeated application of intensive regimens including alkylating agents combined with high-dose antimetabolites, achieving long-term survival rates of over 70–80% with a short treatment course. For large-cell NHL, chemotherapy regimens for T-cell or B-cell NHL can be selected based on immunophenotype. Generally, except for tumors resected in the abdominal cavity and localized non-head-and-neck tumors, prophylactic treatment for the central nervous system is required for all other types of NHL. In addition to systemic intensive chemotherapy, all regimens must include regular triple intrathecal therapy (TIT). Specific regimens are provided below for reference.

(1) Lymphoblastic (T-cell) NHL

1. Stages I and II:

Induction therapy uses the intensive CHOP regimen: CTX 750 mg/m², IV, on days 1 and 22; VCR 1.5 mg/m² (not exceeding 2 mg/m²), IV, once weekly for 4 doses; Pred 40 mg/(m²·d), orally, on days 1–28; ADM 20–40 mg/(m²·d), IV, on days 1 and 22. For primary lesions in the head and neck, triple intrathecal therapy is administered on days 1, 8, and 22. Consolidation therapy involves one course of the CHOP regimen (CTX, VCR, and ADM doses as above, each administered once on day 1; Pred dose as above, on days 1–5). Maintenance therapy: 6-MP 50–75 mg/(m²·d), orally once at bedtime; MTX 25 mg/m², once weekly. Both drugs are continued for 24 weeks, with TIT administered every 6 weeks, indications as above.

2. Stages III and IV:

Treatment is essentially based on the high-risk heat stranguria regimen. Induction therapy uses VDLP plus VP-16 and Ara-C: VCR 1.5 mg/m², once weekly for 4 doses; Pred 40–60 mg/(m²·d), on days 1–28; DNR 30–40 mg/m², on days 1–18; L-ASP 6,000–10,000 U/(m²·dose), every other day starting on day 4, for 9 doses; VP-16 150–200 mg/(m²·dose), IV over 3 hours, followed by Ara-C 300 mg/m², IV over 1 hour, for 3 doses. If the absolute neutrophil count (ANC) <0.5×10⁹ /L, VP-16 + Ara-C therapy may be delayed for several days. TIT is administered on days 1, 22, and 43; if CNS involvement is present at diagnosis, additional doses are given on days 8 and 15. Patients with high tumor burden should first receive a low-dose COP regimen (CTX, VCR, Pred) for 1 week to avoid tumor lysis syndrome. Consolidation and sanctuary therapy involve one course each of the following regimens:

1. CAT regimen: CTX 750 mg/m², IV, on day 1; Ara-C 100 mg/m², divided into two IM doses, on days 1–7; 6-MP 75 mg/(m²·d), once at bedtime, on days 1–7.
2. HD-MTX-CF regimen: MTX 3.0/? times, with intrathecal injection and CF rescue, once every 7-10 days, for a total of 3 times (specific method see high-risk ALL treatment); Oral 6mp 50-75mg/(m2‧d) from day 1 to 7 simultaneously with HD-MTX administration.
3. Reinduction therapy: One course of the original effective induction regimen.
4. Maintenance therapy: 6mp 75mg/(m²‧d), orally, synchronized with MIX 20–30mg/(m²‧dose), once weekly. Insert VP (VCR, Pred) for one week every 3–4 weeks to maintain WBC around 3.0×10⁹/L. Total maintenance therapy duration is 120 weeks.

During maintenance therapy, the following intensified chemotherapy is inserted:

1. HD-MTX plus TIT-CF therapy, once every 8 weeks, for a total of 8 times.
2. Alternate every 3 months with VP-16 plus Ara C therapy and the COAp regimen once.
3. Use the VDLP regimen once every 12 months.

For patients with central nervous system involvement at diagnosis, cranial radiotherapy is administered on the 56th cycle of day and night.

(II) B-cell type NHL (B-NHL/B-ALL-BFM 86 regimen)

Pre-regimen V: CTX 200mg/(m²‧d), intravenous drip over 1 hour, days 1–5; Pred 30mg/(m²‧d), orally, days 1–5.

Regimen A: DEX (dexamethasone) 10mg/(m²‧d), orally, days 1–5; IFO (ifosfamide) 800mg/(m²‧d), intravenous drip over 1 hour, with Mesna (uroprotective agent), days 1–5; MTX 500mg/m², 1/10 dose infused over half an hour, remaining dose infused over 23.5 hours (same below), plus CF (leucovorin) rescue therapy, day 1; VP-16 100mg/m², intravenous drip over 1 hour, days 4–5; Ara C 150mg/(m²‧dose), intravenous drip over 1 hour, q12h, ×4 doses, days 4–5; TIT, day 1 (performed 2 hours after MTX infusion begins, same below).

Regimen B: CTX 200mg/(m²‧d), intravenous drip over 1 hour, days 1–5; MTX 500mg/(m²‧dose), 24-hour intravenous drip (same as above), plus CF rescue, day 1; DEX 10mg/(m²‧d), orally, days 1–5; ADM (adriamycin) 25mg/(m²‧d), intravenous drip over 1 hour, days 4–5; TIT, day 1 (timing same as above).

Regimen AA: DEX 10mg/(m²‧d), orally, days 1–5; VCR 1.5mg/m², intravenous drip over 1 hour; VP-16 100mg/(m²‧d), intravenous drip over 1 hour, days 4–5; Ara C 150mg/(m²‧dose), intravenous drip over 1 hour, q12h, ×4 doses, days 4–5; HD-MTX 5.0/m², 24-hour intravenous drip, plus CF rescue therapy, day 1; IFO 800mg/(m²‧d), intravenous drip over 1 hour, with Mesna, days 1–5; TIT, days 1 and 5 (day 1, timing same as above).

Regimen BB: DEX 10mg/(m²‧d), orally, days 1–5; VCR 1.5mg/m², intravenous drip over 1 hour, day 1; ADM 25mg/(m²‧d), intravenous drip over 1 hour, days 4–5; HD-MTX 5.0/m², same method as above, day 1; CTX 200mg/(m²‧d), intravenous drip over 1 hour, days 1 and 5; TIT, days 1 and 5 (day 1, timing same as above).

For refractory and relapsed high-grade NHL, high-dose chemotherapy followed by hematopoietic stem cell transplantation can be considered. Due to the application of hematopoietic growth factors, hematopoietic recovery after transplantation is relatively rapid. In Europe, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation has largely replaced autologous bone marrow transplantation.

cervical malignancy with cachexia During chemotherapy, precautions and supportive treatments should follow the management of high-risk heat stranguria.