Lymphoma Treatment in Israel

Lymphoma is a malignant disease of the lymphatic system, where tumor cells originate from B- or T-lymphocytes. Modern protocols allow for long-term remission in most patients with classical Hodgkin lymphoma and aggressive diffuse large B-cell lymphoma (DLBCL), and for relapsed and refractory forms, fundamentally new options have emerged — CAR-T cell therapy, bispecific antibodies, and targeted drugs. The Sourasky (Ichilov) Medical Center in Tel Aviv is one of the largest multidisciplinary hospitals in Israel, where lymphomas are treated within the framework of hematologic oncology according to international guidelines from NCCN and ESMO, with mandatory review of biopsies by a reference hematopathologist, a PET-adaptive strategy, and access to clinical trials. In this article, we discuss how diagnosis at Ichilov differs from "home" practices, which protocols are used for different subtypes — Hodgkin lymphoma, DLBCL, follicular, mantle cell, and primary central nervous system lymphoma — and what the patient journey from the CIS looks like from the first inquiry to the follow-up PET-CT six months after therapy completion.

What is this disease

Lymphomas are a heterogeneous group of lymphoid tissue tumors, which are conditionally divided into Hodgkin lymphoma (about 10-15% of all cases) and non-Hodgkin lymphomas (85-90%). Within non-Hodgkin lymphomas, B-cell lymphomas (about 85%) and T/NK-cell lymphomas (about 15%) are distinguished. The WHO classification of 2022 identifies over 100 separate nosological forms, but clinically the main subtypes most commonly encountered at Ichilov are: classical Hodgkin lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma (including MALT), primary CNS lymphoma, Burkitt lymphoma, and peripheral T-cell lymphomas.

The epidemiology worldwide looks approximately as follows: non-Hodgkin lymphomas account for about 6 cases per 100,000 population per year for men and about 4 for women, while Hodgkin lymphoma accounts for about 2-3 cases per 100,000. Incidence increases with age (the median for DLBCL is 65-70 years), but Hodgkin lymphoma has two peaks — young age (15-35 years) and elderly (after 55). The young age of many Hodgkin patients makes the issue of long-term treatment toxicity (cardiotoxicity of anthracyclines, secondary tumors after mediastinal radiation) particularly sensitive — and this is why modern protocols emphasize PET-adaptive de-escalation of therapy.

Risk factors partially depend on the subtype. For Hodgkin lymphoma, the likelihood is increased by Epstein-Barr virus infection (EBV-associated subtypes), family history, and HIV. For DLBCL and other aggressive B-cell lymphomas — immunosuppression (after organ transplantation, HIV), autoimmune diseases (Sjögren's syndrome, celiac disease, rheumatoid arthritis), chronic Helicobacter pylori infection (risk of gastric MALT lymphoma), HCV. For T-cell variants, HTLV-1 (endemic in certain regions) and prolonged celiac disease are important. There are few hereditary syndromes that guarantee lymphoma (ataxia-telangiectasia, Wiskott-Aldrich syndrome), but familial clustering of cases occurs.

Clinical manifestations depend on which lymph nodes or extranodal tissues are affected. Classic signs include painless enlargement of lymph nodes (cervical, supraclavicular, axillary, inguinal) persisting for more than 3-4 weeks without an obvious infectious cause. The so-called "B-symptoms" — unexplained fever above 38 °C, night sweats with soaking of clothes, loss of more than 10% of body weight over 6 months — are important for staging and prognosis (stage is designated with the letter B if they are present). Mediastinal masses may cause cough, shortness of breath, and superior vena cava syndrome. Bone marrow involvement may lead to cytopenias, weakness, and bleeding. In primary CNS lymphoma, the clinical picture is often neurological: behavioral changes, headache, focal deficits, seizures. In gastric lymphoma (MALT) — dyspepsia, a feeling of fullness, occasionally bleeding. Due to such diversity, many CIS patients arrive at Ichilov after several months of examinations without a clear diagnosis — and the first thing the clinic does is recheck the initial biopsy.

Diagnosis at Ichilov Clinic

The diagnosis of lymphoma at Sourasky is based on two principles: first, the diagnosis is made by excisional biopsy of the lymph node (or representative core biopsy of the extranodal lesion), not by "fine-needle aspiration"; second, a mandatory element is the reference review of histology by a hematopathologist specializing in lymphomas. According to the clinic's experience, in 10-20% of patients arriving with a diagnosis of "lymphoma," the subtype changes after revision (for example, DLBCL is reclassified as Burkitt lymphoma or vice versa, follicular lymphoma as mantle cell lymphoma), which fundamentally changes the protocol.

The standard diagnostic package at Ichilov includes several blocks. The histological block involves preparing new sections from paraffin blocks (or, if absent, repeat biopsy), immunohistochemistry of an extended panel (CD20, CD3, CD5, CD10, CD15, CD30, BCL2, BCL6, MUM1, Ki-67, cyclin D1 — depending on the suspected subtype), and if necessary, FISH for MYC, BCL2, BCL6 translocations (to distinguish high-grade B-cell lymphomas of the double-hit type from classical DLBCL), molecular studies for IGH/TCR clonality, and subtype determination by cell origin (GCB vs non-GCB, according to the Hans algorithm). For Hodgkin lymphoma, CD30 expression and EBV status (LMP1, EBER) are checked.

Instrumental staging relies on PET-CT with 18F-fluorodeoxyglucose — this is the standard for all FDG-avid lymphomas (Hodgkin, DLBCL, follicular, mantle cell). PET-CT at Ichilov is performed on modern machines with reduced radiation dose, and the result is evaluated using the 5-point Deauville scale (accepted for interim-PET and response assessment). For non-follicular indolent lymphomas with low FDG avidity, CT of the neck, chest, abdomen, and pelvis with contrast is used. MRI of the brain is mandatory when primary CNS lymphoma is suspected, in the presence of neurological symptoms, or in aggressive lymphomas with a high risk of CNS involvement.

The bone marrow is assessed by trephine biopsy and aspirate with flow cytometry and immunohistochemistry; for Hodgkin lymphoma, if the PET of the bone marrow is negative, biopsy is often not required. Lumbar puncture with cytology and flow cytometry of cerebrospinal fluid is mandatory for primary CNS lymphoma, Burkitt lymphoma, high-risk DLBCL (according to the CNS-IPI index), and testicular lymphoma. Cardiac evaluation (ECG, echocardiogram assessing ejection fraction, if necessary — global longitudinal strain) is performed before starting anthracycline-containing therapy — this is crucial for planning the dose of doxorubicin. Lung function is assessed (spirometry, diffusion capacity DLCO) before prescribing bleomycin. Hepatitis B and C, HIV are checked, and in the case of HBV+ status, prophylactic antiviral therapy is prescribed. For young patients, fertility preservation is discussed — sperm cryopreservation for men, GnRH agonists and/or oocyte cryopreservation for women.

Typical diagnostic timelines: biopsy review — 3-5 working days, PET-CT and MRI — within the first week, complete staging picture and multidisciplinary board decision — 7-10 working days. This is significantly faster than in most public systems in the CIS, allowing therapy to begin without delay.

Treatment Methods

The choice of protocol is determined by the subtype of lymphoma, stage according to the Lugano classification (I-IV), international prognostic index (IPI for aggressive B-cell lymphomas, FLIPI for follicular, MIPI for mantle cell), age, comorbidities, and interim-PET results. Ichilov practices a PET-adaptive strategy — that is, the plan after 2-3 cycles is refined based on how deeply the tumor responded.

Classical Hodgkin lymphoma, early stages (I-II without risk factors). The standard is 2-4 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by involved-site radiation of 20-30 Gy. If the interim-PET is negative after 2 cycles, de-escalation is considered — omitting bleomycin after 2 cycles (AVD), which reduces the risk of pulmonary toxicity while maintaining comparable efficacy. The 5-year progression-free survival for stages I-II traditionally exceeds 80%.

Hodgkin lymphoma, advanced stages (III-IV) or unfavorable II. Options: 6 cycles of ABVD; escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) — more aggressive and toxic, but with a higher percentage of complete responses, used in young patients with poor prognosis; A+AVD — combination of brentuximab vedotin (Adcetris) with AVD, replacing bleomycin with the anti-CD30 antibody-drug conjugate — FDA/EMA standard for advanced stage in some patients. If interim-PET is positive (Deauville 4-5 after 2 cycles) — escalation: switching from ABVD to BEACOPP or adding brentuximab.

Relapsed/refractory Hodgkin lymphoma. The first line of "salvage" is chemotherapy (DHAP, ICE, IGEV, bendamustine) followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT). For patients whose tumors retain CD30, brentuximab vedotin is effective both as a standalone treatment and in combinations (e.g., brentuximab + bendamustine). A powerful class — PD-1 checkpoint inhibitors: nivolumab and pembrolizumab. They have shown high activity in refractory classical Hodgkin lymphoma and are used both alone and in combination with brentuximab.

Diffuse large B-cell lymphoma (DLBCL) in the first line. The historical standard is 6 cycles of R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisone). Since 2022, for patients with IPI 2 and above, POLA-R-CHP has become the standard in several recommendations — replacing vincristine in CHOP with polatuzumab vedotin (an antibody against CD79b with monomethyl auristatin), which according to the POLARIX study increases 2-year progression-free survival by approximately 6-7 percentage points. For double-hit and triple-hit lymphomas (MYC + BCL2 and/or BCL6 rearrangements), more intensive protocols like DA-EPOCH-R are used. For high risk of CNS involvement according to the CNS-IPI index, prophylaxis is added — high-dose methotrexate systemically or intrathecally.

Relapsed/refractory DLBCL. For potentially transplantable patients — 2-3 cycles of second-line chemotherapy (R-DHAP, R-ICE, R-GDP) and, if chemosensitive, auto-HSCT. For patients whose tumors are primarily refractory or relapse within the first 12 months, the modern standard is CAR-T cell therapy in the second line: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), or lisocabtagene maraleucel (Breyanzi). This is personalized therapy, where T-lymphocytes are isolated from the patient's blood, genetically modified to express a chimeric antigen receptor against CD19, and returned to the body. For non-transplantable and post-CAR-T patients, bispecific antibodies (epcoritamab, glofitamab — CD20xCD3), loncastuximab tesirin (anti-CD19 ADC), and targeted therapy with tazemetostat in EZH2-mutated cases are available.

Follicular lymphoma. In asymptomatic cases with low tumor mass, a "watch and wait" strategy is often chosen — early treatment does not improve overall survival. In cases of high tumor mass (GELF criteria), the first line is R-CHOP, R-B (rituximab + bendamustine), R-CVP, or O-B (obinutuzumab + bendamustine); obinutuzumab — a second-generation anti-CD20 antibody with enhanced ADCC effect — has shown an advantage in progression-free survival according to the GALLIUM study. Maintenance therapy with rituximab every 2 months for 2 years is standard for responding patients. In relapses: R-B if not previously used, obinutuzumab, lenalidomide + rituximab (R2), targeted therapy with EZH2 inhibitors (tazemetostat in EZH2 mutations), CAR-T in the second-third line (axicabtagene, tisagenlecleucel).

Mantle cell lymphoma. Previously considered one of the most unfavorable B-cell lymphomas; over the last decade, prognosis has significantly improved. In young patients ({'<'}65-70 years), the standard is intensive induction (e.g., alternating R-CHOP and R-DHAP or Nordic protocol R-Maxi-CHOP/R-HD-Ara-C) followed by auto-HSCT and maintenance with rituximab. In older patients — R-B, R-CHOP, VR-CAP (bortezomib + R-CHOP). The role of BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) is increasing — they have shown high activity in relapses and increasingly earlier lines; studies are ongoing to include BTK inhibitors in the first line. In relapses after BTK inhibitors, CAR-T therapy (brexucabtagene autoleucel) is available.

Primary CNS lymphoma. A separate aggressive subtype requiring therapy with high doses of methotrexate (3-8 g/m²), which penetrates the blood-brain barrier. The standard induction regimen is MATRix (methotrexate + cytarabine + thiotepa + rituximab) or R-MPV (methotrexate + procarbazine + vincristine + rituximab). In responding young patients — consolidation with high-dose chemotherapy (thiotepa-containing regimens) with auto-HSCT. Whole brain radiotherapy is used less frequently due to neurotoxicity, primarily in non-responders or as salvage. Studies are ongoing for ibrutinib and lenalidomide in relapses.

Radiation therapy. Used as involved-site or involved-node radiotherapy with intensity-modulated radiation therapy (IMRT), stereotactic radiosurgery for individual CNS lesions. The modern trend is to reduce doses (20-30 Gy for Hodgkin, 24-30 Gy for aggressive lymphomas, 24 Gy for indolent) and to maximize targeted fields to reduce long-term toxicity. For mediastinal volumes in young women, proton therapy is considered (available at partner centers) to reduce the dose to the heart and breasts.

Treatment Program — Stages

The program for international patients at Sourasky is built sequentially. Stage 1 — preliminary correspondence: the patient sends discharge summaries, histological slides (or paraffin blocks), disks with PET-CT/CT/MRI. The international department organizes a preliminary conclusion from a hematologist-oncologist and an estimate. Stage 2 — arrival in Tel Aviv: in-person consultation with the leading specialist on the first or second day, blood draw, and if necessary — repeat imaging and biopsy. Stage 3 — reference review of histology in Ichilov's pathology laboratory, additional IHC and molecular tests. Stage 4 — multidisciplinary board (tumor board): hematologist-oncologist, radiation therapist, pathomorphologist, and if necessary — surgeon, neurologist, cardiologist, transplant specialist. Stage 5 — standardized treatment protocol on paper, signed by the patient. Stage 6 — start of therapy: most chemotherapy cycles are conducted on an outpatient basis, hospitalization is needed for the first infusions, complications, and for intensive regimens (high-dose methotrexate, BEACOPP, auto-HSCT, CAR-T). Stage 7 — interim-PET usually after 2-3 cycles, response assessment, and if necessary — protocol adjustment. Stage 8 — completion of therapy, final PET-CT. Stage 9 — surveillance: follow-up visits in the first 2 years every 3 months, then every 6-12 months, with gradual desensitization. Some follow-up examinations can be conducted at the patient's place of residence, with telemedicine consultation from Ichilov based on the results.

Prices and Costs

Prices for lymphoma treatment at Ichilov depend on the subtype, stage, need for transplantation or CAR-T therapy, and which drugs are included in the protocol. Below are approximate ranges in US dollars as of the current clinic tariff sheet; the final estimate is always personalized and approved before treatment begins.

• Initial consultation with the leading hematologist-oncologist — about 600-750 USD.
• Reference review of histology with extended IHC — about 700-1500 USD; FISH panel — an additional 400-800 USD per study.
• Whole body PET-CT — about 1500-2000 USD; brain MRI with contrast — about 900-1300 USD.
• Complete diagnostic package "turnkey" (biopsy review, PET, MRI, laboratory, board) — usually in the range of 8000-14,000 USD.
• One cycle of R-CHOP or POLA-R-CHP (outpatient, without complications) — in the range of 6000-15,000 USD, six cycles — respectively 35,000-90,000 USD; the range is primarily explained by the cost of polatuzumab and brentuximab.
• ABVD/A+AVD — from 4000-8000 USD per cycle for ABVD and significantly higher with the addition of brentuximab.
• Course of treatment with nivolumab/pembrolizumab — from 15,000-25,000 USD per cycle including the drug.
• Autologous stem cell transplantation (auto-HSCT) — approximately 90,000-140,000 USD "turnkey" with hospitalization.
• CAR-T therapy — the most expensive section, approximately 450,000-600,000 USD, including drug production, hospitalization in a specialized ward, and management of complications (CRS, ICANS).
• Involved-site radiation therapy (10-20 sessions) — usually 12,000-25,000 USD.

Exact figures depend on the current exchange rate of the shekel and changes in the tariff sheet; the final estimate is approved in writing by the international department before the start of each stage.

Leading Doctors in the Field

Lymphomas at Sourasky are handled by the hematologic oncology department in conjunction with the lymphoma and cell therapy unit. The team includes several hematologist-oncologists with narrow specialization (Hodgkin lymphoma, aggressive B-cell lymphomas, indolent lymphomas, T-cell lymphomas, CNS lymphomas), specialists in bone marrow and cell therapy (including CAR-T), radiation therapists focused on hematologic tumors, a specialized hematopathologist, and a clinical research coordinator. Each international patient is assigned a leading physician according to their subtype and a Russian-speaking coordinator.

The specific leading physician is selected based on the patient's diagnosis — for example, for primary CNS lymphoma, it will be a specialist with experience in high-dose methotrexate therapy and collaboration with neuro-oncologists, while for refractory DLBCL, it will be a physician working in the CAR-T program. The current list of specialists, their publications, and experience are sent by the clinic's international department along with the preliminary conclusion. This approach provides the patient not with a "known name in general," but specifically with the doctor who daily manages similar patients.

FAQ

What language is used for communication with the doctor and in the hospital?

The appointment with the leading hematologist-oncologist is conducted in English or Hebrew with a Russian-speaking medical translator organized by the clinic's international department. Day hospital nurses and chemotherapy department staff often speak Russian (a significant portion of medical personnel in Israel are repatriates from the CIS). All discharge summaries, treatment programs, and informed consents are provided in Russian or translated in advance.

What documents need to be sent for a preliminary conclusion?

The optimal package: discharge summaries from the hospital and outpatient records, histology report with immunohistochemistry, paraffin blocks or unstained biopsy sections (for reference), disks with PET-CT/CT/MRI in DICOM format, recent blood tests, ECG, and echocardiogram, list of current medications. If something is missing — tests can be done upon arrival in Tel Aviv, but histology review requires at least slides.

How long does treatment take and do I need to stay in Israel for the entire course?

The full course of R-CHOP or ABVD takes about 4-5 months (6 cycles every 3 weeks plus breaks). The first 1-2 cycles and response assessment are preferably conducted at Ichilov; subsequent cycles can often be continued at the patient's place of residence under remote clinic supervision — this option is discussed at the board. Auto-HSCT requires 4-6 weeks of continuous stay in Tel Aviv, CAR-T therapy — about 6-8 weeks with mandatory presence within 30-60 minutes of the clinic during the first month after infusion.

Is a deposit required before starting treatment?

Yes, the work with international patients is organized on a "deposit + recalculation" model: a deposit is made before arrival for the estimate of the first stage (diagnostics or first block of therapy). At the end of each stage, the bill is closed based on actual services, and any unused balance is carried over to the next stage or refunded. No procedures are performed without prior agreement on the estimate.

What is a tumor board and is it mandatory?

A multidisciplinary tumor board is a meeting where your case is discussed by a hematologist-oncologist, pathomorphologist, radiation therapist, and other specialists, where the final protocol is approved. For lymphomas, the tumor board is mandatory and takes place weekly at Ichilov; the conclusion is signed by all participants and provided to the patient.

Can I get a second opinion on an existing diagnosis without coming to Tel Aviv?

Yes. The "second opinion" format is available remotely: you send slides and disks, the clinic conducts a reference histology review and consults remotely on the protocol; the conclusion comes in the form of an official medical report. If the second opinion confirms the need to come — the paid service is usually credited towards the cost of the further program.

Do CIS insurance policies work at Ichilov?

Basic OMS from CIS countries do not apply in Israel. Private insurances categorized as "international medical insurance" sometimes cover part of the treatment — this is resolved individually between the patient, insurer, and the clinic's financial department. For most patients from the CIS, the actual model is direct payment with subsequent provision of closing documents to the insurer.

What is follow-up and how is it organized after returning home?

Follow-up after therapy completion for lymphomas typically lasts at least 5 years: the first 2 years — check-ups every 3 months, then every 6 months, after 5 years — once a year. It includes clinical examination, tests, and if necessary — PET-CT or CT. Some visits may occur at the place of residence with telemedicine consultation from Ichilov based on the results; key points (one year after therapy completion, 2 years, 5 years) many patients prefer to undergo in person in Tel Aviv.

How to obtain a treatment program

To receive a preliminary treatment program and estimate from the hematologic oncology department of Sourasky (Ichilov) clinic in Tel Aviv, please submit a request through the form on the website or write to the coordinator. In the request, briefly describe: the subtype and stage of lymphoma (if known), what treatment has already been conducted, what drugs were used, response to therapy, and comorbidities. Attach key documents — histology, recent PET-CT or CT, latest blood tests, echocardiogram. Within 1-3 working days, a Russian-speaking medical coordinator will contact you, ask clarifying questions, and organize the transfer of materials to the leading specialist for your lymphoma subtype. You will receive a preliminary conclusion with a plan for further actions and an approximate estimate in writing before making a decision to come, without obligations. If you decide to be treated at Ichilov, the coordinator assists with visa arrangements (if required), booking accommodation near the clinic, airport pickup, and translation services.