The first 60 days

Acute lymphoblastic leukaemiaAcute lymphoblastic leukaemia is the childhood cancer success story, and was the first disease treated with CAR-T and with a T-cell engager.

Acute myeloid leukaemiaAcute myeloid leukaemia is an aggressive blood cancer where, after 40 years of the same chemotherapy, a wave of targeted drugs (FLT3, IDH, BCL-2, menin) arrived.

Acute myeloid leukaemia in older or unfit patientsMost people with acute myeloid leukaemia are over 65, and many cannot take intensive chemotherapy. Venetoclax with azacitidine, two gentler drugs, doubled remission rates and lengthened life in this group, replacing the old choice between supportive care and low-dose chemotherapy.

Acute promyelocytic leukaemiaAcute promyelocytic leukaemia is caused by a single fused gene that freezes blood cells at an immature stage and triggers dangerous bleeding. Two non-chemotherapy drugs, a vitamin A derivative and arsenic trioxide, make the cells mature and cure more than nine in ten patients.

Adult T-cell leukaemia/lymphomaA T-cell lymphoma caused by a virus, HTLV-1, which is usually caught in infancy through breast milk and causes the lymphoma decades later in a small minority of the people it infects. It occurs in people from south-western Japan, the Caribbean, west and central Africa, parts of South America, Iran and Romania, and it comes in four forms that are treated very differently.

Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia)Advanced systemic mastocytosis is the dangerous form of this rare blood cancer, in which KIT-mutant mast cells damage the marrow, liver, gut or bones, grow alongside a second blood cancer such as chronic myelomonocytic leukaemia, or flood the blood as mast cell leukaemia. The KIT-blocking tablets midostaurin and avapritinib have replaced older chemotherapy, and fit patients may have a transplant.

Advanced-stage classical Hodgkin lymphoma (stage III to IV)Advanced-stage classical Hodgkin lymphoma is Hodgkin lymphoma involving nodes on both sides of the diaphragm or organs such as the liver, lungs or bone marrow. It is treated with six cycles of combination chemotherapy, and two trials changed the standard: replacing bleomycin with brentuximab vedotin (ECHELON-1) and then with nivolumab (SWOG S1826), which cured more patients with less toxicity.

ALK-negative anaplastic large cell lymphomaAn aggressive T-cell lymphoma that looks like its ALK-positive sibling under the microscope and carries the same CD30 marker, but lacks the broken ALK gene. It affects older people and is cured less often, and several genetic changes inside it predict very different outcomes.

ALK-positive anaplastic large cell lymphomaAn aggressive T-cell lymphoma, mostly of children and young adults, whose cells carry a broken ALK gene and a protein called CD30 on the surface. Despite looking alarming down the microscope it is the T-cell lymphoma most often cured, and both of its markers are things that drugs can aim at.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN)Blastic plasmacytoid dendritic cell neoplasm is a rare aggressive leukaemia-like blood cancer of dendritic-cell precursors, a few hundred US cases a year, that often first appears as bruise-like skin lesions. Two CD123-directed drugs, tagraxofusp and pivekimab sunirine, are the first targeted therapies; allogeneic transplant in first remission is still the only route to long-term control.

Breast implant-associated anaplastic large cell lymphomaA rare lymphoma that grows in the scar capsule the body forms around a breast implant, usually many years after the operation, and usually shows itself as sudden swelling of the breast from fluid around the implant. It is linked to textured implants, and when it is confined to the capsule it is usually cured by removing the implant and the capsule whole.

Burkitt leukaemiaBurkitt leukaemia is Burkitt lymphoma presenting mainly in the bone marrow and blood, so that it looks like acute lymphoblastic leukaemia but is a mature B-cell cancer driven by the MYC gene. It is treated as Burkitt lymphoma, with short, very intensive chemotherapy plus rituximab and protection of the brain, and most children and many adults are cured.

Burkitt lymphomaBurkitt lymphoma is the fastest-growing human tumour, driven by a single rearrangement that switches on the MYC gene. That speed makes it exquisitely sensitive to chemotherapy: short, intense courses, now with the antibody rituximab, cure the great majority of children in well-resourced settings. The remaining task is to bring the same cure to the African children who make up most cases.

Chronic lymphocytic leukaemiaA slow leukaemia that no longer needs chemotherapy: BTK inhibitors and venetoclax control it for years, often in fixed-duration courses.

Chronic lymphocytic leukaemia, first treatmentChronic lymphocytic leukaemia is treated only when it causes problems, and chemotherapy has gone. The first treatment is now either a BTK inhibitor taken indefinitely or a one-year course of venetoclax with obinutuzumab (CLL14), and the two can be combined for a fixed course.

Chronic myeloid leukaemia (CML)Chronic myeloid leukaemia is a blood cancer driven by a single fused gene, BCR-ABL1, and the model for oncogene-targeted treatment: imatinib in 2001 and the tyrosine kinase inhibitors that followed turned it into a condition most people live with long-term. About half of patients with a sustained deep molecular response can now stop treatment altogether.

Chronic myeloid leukaemia, accelerated and blast phaseChronic myeloid leukaemia can accelerate and then transform into an acute leukaemia called blast crisis. Tyrosine kinase inhibitors are given at full strength, combined with acute leukaemia chemotherapy in blast phase, to bring the disease back to chronic phase quickly enough for a donor stem cell transplant, the only treatment that cures it.

Chronic myeloid leukaemia, chronic phaseChronic-phase chronic myeloid leukaemia is the disease that imatinib turned from fatal into manageable: a daily pill blocks the BCR::ABL1 protein that drives it. Blood tests track the leukaemia gene to a millionth, newer pills such as asciminib (ASC4FIRST) reach deeper responses faster, and patients with years of undetectable disease can try stopping.

Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasmsChronic myelomonocytic leukaemia and its relatives are bone-marrow cancers that behave partly like myelodysplasia (poorly made blood cells) and partly like a proliferative disease (an excess of monocytes or platelets). Hypomethylating agents produce responses in a minority and stabilise counts in more, transplant can cure the fit, and RAS-pathway and JAK inhibitors are in trials.

Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)Cutaneous T-cell lymphoma is a family of nine lymphomas that start in the skin and mostly stay there, of which mycosis fungoides is by far the commonest. Most of them are long-term skin conditions managed over decades rather than cancers that are cured or not cured, and two of the nine are genuinely aggressive.

Diffuse large B-cell lymphomaDiffuse large B-cell lymphoma (DLBCL) is an aggressive but curable lymphoma. CAR-T cures about 40% of relapsed patients, and off-the-shelf bispecifics are now approved.

Early-stage classical Hodgkin lymphoma (stage I to II)Early-stage classical Hodgkin lymphoma is Hodgkin lymphoma confined to one or two lymph node regions on one side of the diaphragm, one of the most curable cancers, with most patients cured by a short course of ABVD chemotherapy with or without radiotherapy to the involved nodes. Because patients are young, trials now use PET scans after two cycles to give as little treatment as safely possible.

EBV-positive diffuse large B-cell lymphomaA diffuse large B-cell lymphoma in which Epstein-Barr virus, the virus of glandular fever, is present in the tumour cells. It is diagnosed by a stain on the biopsy, it is commoner in east Asia and Latin America than in Europe, and it is treated in the same way as diffuse large B-cell lymphoma without the virus.

Enteropathy-associated T-cell lymphomaAn aggressive T-cell lymphoma of the small bowel that arises out of coeliac disease, usually in somebody whose coeliac disease was diagnosed late or has not responded to a gluten-free diet. It often announces itself as a perforation or obstruction of the bowel in a person who is already underweight, which is why treatment has to deal with nutrition at the same time as the lymphoma.

Erdheim-Chester diseaseErdheim-Chester disease is a rare histiocytosis, a cancer-like overgrowth of immune cells called histiocytes that scar the long bones, the tissue around the kidneys and heart, the brain and the skin. Most cases carry the BRAF V600E mutation or another fault in the same growth pathway, and the melanoma drugs vemurafenib and cobimetinib now control the disease in most patients.

Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasmsHistiocytoses are diseases in which immune scavenger cells build up in bone, heart, brain, kidneys and skin. They used to be treated as inflammatory conditions with steroids and interferon. The discovery that most carry mutations in the same growth pathway as melanoma turned them into targetable cancers: BRAF and MEK inhibitor pills now produce responses in nearly every treated patient.

Essential thrombocythaemia (ET)Essential thrombocythaemia is a slow blood cancer in which the marrow makes too many platelets. Most people need only aspirin and monitoring; those at higher risk of clots take a drug to lower the platelet count, usually hydroxyurea or interferon, with anagrelide in reserve.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)MALT lymphoma is a slow-growing lymphoma that starts in lymphoid tissue lining an organ, most often the stomach, where it is usually caused by long-standing Helicobacter pylori infection and can be cured with antibiotics alone. Other sites include the eye socket, salivary glands, thyroid, lung and skin; localised disease is treated with low-dose radiotherapy and widespread disease with rituximab.

Extranodal NK/T-cell lymphomaAn aggressive lymphoma of natural killer cells, always driven by Epstein-Barr virus, that destroys the tissues in the middle of the face: the nose, the palate and the sinuses. It is common in east Asia and Latin America and uncommon in Europe, and it is the one lymphoma in which ordinary anthracycline chemotherapy does not work at all.

FLT3-mutated acute myeloid leukaemiaFLT3-mutated acute myeloid leukaemia carries a mutation in a growth-signal receptor that makes the leukaemia relapse quickly. Adding a FLT3 blocker to chemotherapy, midostaurin or quizartinib, lengthens life, and gilteritinib is the standard when the disease comes back.

Follicular lymphomaFollicular lymphoma is the most common slow-growing lymphoma, defined in about 85% of cases by a BCL2 translocation. Most people live with it for decades, treated only when it causes problems; it can be controlled repeatedly with anti-CD20 antibodies, chemotherapy, bispecifics or CAR-T but rarely cured, and a small share transform into an aggressive lymphoma each year.

Gastric MALT lymphomaA slow-growing MALT lymphoma that grows in the lining of the stomach, usually caused by a long-standing infection with the bacterium Helicobacter pylori. It is the one lymphoma that is often cured by a fortnight of antibiotics, and a single chromosome change predicts the minority in whom antibiotics will not work.

Hairy cell leukaemiaHairy cell leukaemia is a rare, slow B-cell leukaemia with a single defining mutation (BRAF V600E) that is unusually curable: one week of a purine analogue puts most people into remission for years, and BRAF drugs rescue those who relapse.

Hepatosplenic T-cell lymphomaHepatosplenic T-cell lymphoma is a rare, very aggressive lymphoma of young men in which gamma-delta T cells fill the liver, spleen and bone marrow without forming lumps in the nodes. It is linked to long-term immune suppression, above all thiopurines with or without anti-TNF drugs for inflammatory bowel disease, and is treated with intensive chemotherapy then a stem cell transplant where possible.

High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma)An aggressive B-cell lymphoma defined not by how it looks but by two genetic faults in the same cell: a rearrangement of MYC, which drives growth, and one of BCL2, which blocks the cell from dying. It behaves worse than ordinary diffuse large B-cell lymphoma, so finding the rearrangements changes the treatment.

Higher-risk myelodysplastic syndromesHigher-risk myelodysplastic syndromes behave like a slow leukaemia and often become one. Azacitidine lengthens life and a donor stem cell transplant is the only cure; every attempt to improve on azacitidine in a large trial, including the venetoclax combination tested in VERONA, has so far failed.

HIV-associated (AIDS-related) lymphomasPeople living with HIV have a raised risk of aggressive lymphomas, driven by immune suppression and viruses such as Epstein-Barr virus. The transformation of the last two decades is that, with antiretroviral therapy continued through treatment, these lymphomas are treated with the same full-dose chemotherapy and antibody regimens as in anyone else, with similar chances of cure.

Hodgkin lymphomaHodgkin lymphoma is one of the most curable cancers, where the goal is now to cure with less toxicity, using brentuximab and, from 2026, first-line nivolumab.

IDH1- and IDH2-mutated acute myeloid leukaemiaIDH-mutated acute myeloid leukaemia has a faulty metabolic enzyme that floods cells with a chemical that blocks maturation. Pills that shut the enzyme off, ivosidenib for IDH1 and enasidenib or olutasidenib for IDH2 and IDH1, let the leukaemia cells mature, and ivosidenib with azacitidine tripled survival in older patients.

Indolent and smouldering systemic mastocytosisIndolent systemic mastocytosis is the common, slow form of this rare blood disorder, in which KIT-mutant mast cells build up in the marrow and skin and release histamine that causes flushing, itching, stomach pain, bone thinning and sometimes severe allergic reactions. Life expectancy is near normal, antihistamines and adrenaline control symptoms, and low-dose avapritinib was approved in 2023.

Intravascular large B-cell lymphomaIntravascular large B-cell lymphoma is a rare form of large B-cell lymphoma in which the cancer cells grow inside small blood vessels rather than forming lumps, so it causes fevers, confusion, skin patches or breathlessness and is often found late or only after death. Rituximab-based chemotherapy with drugs that reach the brain has turned a nearly always fatal disease into one often controlled.

Leukaemia (all types)Leukaemia means cancer of the blood-forming cells, but the four main types share little beyond the name: acute lymphoblastic and acute myeloid leukaemia are emergencies treated with intensive therapy, while chronic lymphocytic and chronic myeloid leukaemia are slow diseases controlled for years with pills. Each has its own page.

Lower-risk myelodysplastic syndromesLower-risk myelodysplastic syndromes rarely turn into leukaemia quickly; the problem is anaemia and the transfusions it demands. Erythropoietin, then luspatercept (COMMANDS) and the telomerase blocker imetelstat (IMerge), free many patients from transfusions for months or years, and lenalidomide does the same for the del(5q) subtype.

Lymphomatoid granulomatosisLymphomatoid granulomatosis is a rare Epstein-Barr virus-driven disease of B cells that invades and destroys blood vessels, almost always in the lungs and often the brain and skin, in people whose immune control of the virus is weak. Low-grade disease can be treated with interferon and high-grade disease as a large B-cell lymphoma with rituximab-based chemotherapy.

Lymphomatoid papulosisA skin condition that keeps producing crops of small red bumps which ulcerate, crust and heal on their own over a few weeks, leaving small scars, and then come back. The biopsy looks like an aggressive lymphoma and the disease behaves nothing like one: nobody in the published series has died of it, but it carries a raised risk of a second lymphoma.

Mantle cell lymphomaAn uncommon B-cell lymphoma driven by cyclin D1 that used to behave badly in almost everyone. BTK inhibitors, CAR-T and now BCL2 drugs have changed it from chemotherapy-plus-transplant to targeted combinations.

Marginal zone lymphomaMarginal zone lymphoma is a slow B-cell lymphoma that often grows where the body has been fighting a chronic infection: the stomach with Helicobacter pylori, the eye, the skin or the spleen. Curing the infection cures many early cases; the rest are treated with rituximab, chemotherapy or BTK inhibitors.

Mediastinal grey zone lymphomaA lymphoma of the chest that sits between two diseases: it has some of the features of primary mediastinal B-cell lymphoma and some of classic Hodgkin lymphoma, and a pathologist cannot put it cleanly in either. It is recognised as an entity of its own, and the 2022 classifications restricted the name to lymphomas that involve the mediastinum.

Mixed-phenotype acute leukaemiaMixed-phenotype acute leukaemia is a rare acute leukaemia whose cells carry markers of both lymphoid and myeloid lines, so it fits neither acute lymphoblastic nor acute myeloid leukaemia. Pooled evidence favours starting with the drugs used for acute lymphoblastic leukaemia, adding a targeted drug when the Philadelphia chromosome is present, and a stem cell transplant in first remission.

Monomorphic epitheliotropic intestinal T-cell lymphomaAn aggressive T-cell lymphoma of the small bowel that looks and presents much like the lymphoma that complicates coeliac disease but has no connection with coeliac disease at all. It was separated out of that diagnosis in 2016, it is made of monotonous small to medium cells, and it often presents with perforation or obstruction of the bowel.

Multiple myelomaMultiple myeloma is a plasma-cell cancer with more new drug classes than any other: proteasome inhibitors, IMiDs, CD38 antibodies, BCMA CAR-T, bispecifics, and an ADC.

Mycosis fungoidesThe commonest cutaneous T-cell lymphoma, and a disease that behaves like a long-term skin condition for most of the people who have it: flat scaly patches that have often been treated as eczema or psoriasis for years before anyone takes a biopsy. In its early stages life expectancy is close to normal, and the treatment is creams and light rather than chemotherapy.

Myelodysplastic syndromes / neoplasms (MDS)Bone-marrow disorders where blood cells are made badly and too few reach the blood; a third progress to acute leukaemia. Treatment ranges from transfusions and growth factors to hypomethylating drugs and, for the fit, transplant.

Myeloid leukaemia of Down syndromeMyeloid leukaemia of Down syndrome is a form of acute myeloid leukaemia in young children with Down syndrome, driven by a GATA1 mutation on top of the extra chromosome 21 and often preceded by a transient leukaemia-like illness in the newborn. Its cells are unusually sensitive to chemotherapy, so children are cured about nine times in ten with gentler treatment than other childhood leukaemia.

Myeloproliferative neoplasms (PV, ET, myelofibrosis)Myeloproliferative neoplasms are slow-growing blood cancers in which the marrow overproduces red cells (polycythaemia vera), platelets (essential thrombocythaemia) or scar tissue (myelofibrosis). Almost all carry a mutation in JAK2, CALR or MPL; treatment aims to prevent clots and control symptoms, and only transplant cures myelofibrosis.

Newly diagnosed multiple myeloma, transplant-eligibleFit patients with newly diagnosed myeloma receive four drugs at once, then their own stem cells are collected, they are given high-dose chemotherapy, the cells are returned and they continue on maintenance. Adding the CD38 antibody daratumumab to the three-drug backbone, tested in PERSEUS and CASSIOPEIA, means most patients now reach a state where no myeloma can be detected.

Newly diagnosed multiple myeloma, transplant-ineligibleMost people with newly diagnosed myeloma are too old or frail for a stem cell transplant. Combining a CD38 antibody with lenalidomide and dexamethasone (MAIA) and, for the fitter, with bortezomib as well (IMROZ), now keeps the disease away for around five years in many and lengthens life.

Nodal marginal zone lymphomaNodal marginal zone lymphoma is a slow-growing lymphoma of the lymph nodes that looks like the MALT and splenic types under the microscope but has no organ or spleen involvement to explain it. It lacks a diagnostic marker, so it is diagnosed by excluding the other small B-cell lymphomas, and it is treated like follicular lymphoma with rituximab-based therapy.

Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma)Angioimmunoblastic T-cell lymphoma, now called nodal T-follicular helper cell lymphoma of angioimmunoblastic type, is one of the commonest T-cell lymphomas and mostly affects people over 60. It presents with widespread swollen nodes, fever, rash and immune upsets such as anaemia; about four in ten people are alive five years after chemotherapy, more after a transplant in first remission.

Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma)Nodular lymphocyte-predominant Hodgkin lymphoma is the rare, slow-growing cousin of classical Hodgkin lymphoma, so different in its CD20-bearing cells that the WHO renamed it a B-cell lymphoma in 2022. Early disease is usually cured with radiotherapy alone or surgery in children, advanced disease with rituximab-based chemotherapy, and patients are followed for life because it can return late.

Non-Hodgkin lymphoma (all types)Non-Hodgkin lymphoma is not one disease but a family of more than sixty cancers of the lymphocytes, the white blood cells of the immune system. About 95 per cent come from B cells and the rest from T or NK cells; some grow over years and are watched, others grow over weeks and are treated to cure. The family is the map; the subtype is the disease, and the subtype is what decides the treatment.

NPM1-mutated and KMT2A-rearranged acute myeloid leukaemiaNPM1-mutated and KMT2A-rearranged leukaemias depend on a protein called menin to keep leukaemia genes switched on. Menin inhibitors, revumenib and ziftomenib, are the first drugs to exploit this, and they produce remissions in patients whose leukaemia had come back after everything else.

Ocular adnexal MALT lymphomaA slow-growing MALT lymphoma of the tissues around the eye: the conjunctiva, the eye socket, the tear gland or the eyelid. It usually shows itself as a painless salmon-pink patch on the white of the eye or as an eye that has begun to bulge, and it is controlled in almost everybody, often by a short course of radiotherapy.

Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)Peripheral T-cell lymphomas are lymphomas of T cells rather than B cells. They are rarer, more varied and, apart from a few subtypes, harder to treat than B-cell lymphomas; several new drugs help only defined subtypes.

Plasma cell leukaemiaPlasma cell leukaemia is myeloma in which the cancerous plasma cells spill into the bloodstream in large numbers. It is the most aggressive plasma cell cancer and is treated urgently with several myeloma drugs at once followed by a stem cell transplant.

Plasmablastic lymphomaAn aggressive lymphoma whose cells have taken on the appearance of plasma cells, so they no longer carry the CD20 marker that most B-cell lymphoma treatments aim at. It most often starts in the mouth or jaw, and about half of people diagnosed with it have HIV.

Polycythaemia vera (PV)Polycythaemia vera is a slow blood cancer in which a single faulty gene, JAK2, makes the bone marrow produce too many red cells. Thick blood causes clots, so treatment thins it (blood removal, aspirin) and, for higher-risk patients, calms the marrow with hydroxyurea, interferon or ruxolitinib; a hepcidin mimic, rusfertide, now controls red cell counts without regular blood removal.

Post-transplant lymphoproliferative disorder (PTLD)After an organ or stem cell transplant, the drugs that stop rejection also stop the immune system from policing Epstein-Barr virus, and infected B cells can grow into a lymphoma. The first move is to ease the immunosuppression; then the antibody rituximab, chemotherapy if needed, and, newest of all, off-the-shelf virus-specific T cells that restore the missing immune control.

Primary cutaneous anaplastic large cell lymphomaA cutaneous T-cell lymphoma that appears as one or a few red-purple nodules on the skin, often ulcerated, which may shrink on their own. Despite cells that look alarming under the microscope it stays in the skin in almost everybody and is treated with surgery or local radiotherapy rather than chemotherapy.

Primary cutaneous follicle centre lymphomaPrimary cutaneous follicle centre lymphoma is a slow-growing lymphoma of germinal-centre B cells that stays in the skin, usually as lumps on the head or trunk. Its outlook is excellent, with about 95 in 100 people alive at five years, and radiotherapy or excision is usually all that is needed; the important thing is not to mistake it for the aggressive leg-type large B-cell lymphoma.

Primary cutaneous marginal zone lymphomaPrimary cutaneous marginal zone lymphoma is a very slow-growing lymphoma that appears as pink or purple lumps in the skin, usually on the arms or trunk, and almost never spreads inside the body. WHO-HAEM5 now calls it a lymphoproliferative disorder because it behaves so well; surgery or radiotherapy clears most lesions, and relapses in the skin are common but harmless.

Primary effusion lymphomaA rare lymphoma that grows as fluid rather than as a lump: it fills the space around the lungs, the heart or the bowel without forming a mass. It is caused by Kaposi sarcoma herpesvirus and arises mostly in people with advanced HIV infection, and it is diagnosed by sending the fluid itself for testing.

Primary large B-cell lymphoma of the testisA large B-cell lymphoma that starts in a testicle rather than in a lymph node, usually in a man over 60, and shows itself as a painless swelling. It is the commonest cancer of the testicle in older men, and it behaves as one disease with lymphoma of the brain and of the eye, which is why treatment deliberately protects both.

Primary mediastinal (thymic) large B-cell lymphomaPrimary mediastinal B-cell lymphoma is a fast-growing lymphoma of the thymus behind the breastbone that mostly affects young women. Immunochemotherapy cures about nine in ten, radiotherapy can now be skipped when the end-of-treatment scan is clear, and PD-1 antibodies and CAR-T cells rescue many of those who relapse.

Primary myelofibrosisPrimary myelofibrosis is a blood cancer in which the marrow scars over, the spleen swells and patients become anaemic and exhausted. JAK inhibitors, ruxolitinib first (COMFORT) and then fedratinib, pacritinib and momelotinib (MOMENTUM), shrink the spleen and relieve symptoms; only a donor stem cell transplant can cure it.

Relapsed and refractory classical Hodgkin lymphomaRelapsed or refractory classical Hodgkin lymphoma is Hodgkin lymphoma that comes back or does not respond after first-line chemotherapy. The standard path is salvage chemotherapy, often with brentuximab vedotin or a PD-1 antibody, then high-dose chemotherapy with an autologous stem cell transplant; for those who relapse again, nivolumab and pembrolizumab give lasting control in many.

Relapsed or refractory chronic lymphocytic leukaemiaWhen chronic lymphocytic leukaemia returns, the usual move is to switch drug class: venetoclax-based therapy after a BTK inhibitor, or a BTK inhibitor after venetoclax. Pirtobrutinib (BRUIN) works after the older BTK inhibitors fail, and CAR-T is approved for patients who have run out of both classes.

Relapsed or refractory multiple myelomaMyeloma almost always returns, and each return is harder to treat. Two kinds of immune therapy aimed at the BCMA protein on myeloma cells, CAR-T cells (KarMMa-3, CARTITUDE-4) and off-the-shelf bispecific antibodies (MajesTEC), now give deep remissions after other drugs fail, and a second target, GPRC5D, gives another option.

Richter transformation of chronic lymphocytic leukaemiaRichter transformation is the sudden change of slow chronic lymphocytic leukaemia into a fast-growing lymphoma, usually of the diffuse large B-cell type. It is treated with lymphoma chemotherapy followed by a donor transplant where possible, and newer drugs such as pirtobrutinib, venetoclax combinations and bispecific antibodies are being tested because standard chemotherapy rarely cures it.

Rosai-Dorfman-Destombes diseaseRosai-Dorfman disease is a rare histiocytosis in which large immune cells called histiocytes fill the neck lymph nodes or grow in the skin, bones, nose, brain coverings or kidneys. Many cases fade without treatment, so it is watched unless it threatens an organ, when surgery, steroids, sirolimus or, for the third with a growth-pathway mutation, MEK inhibitors such as cobimetinib are used.

Secondary and therapy-related acute myeloid leukaemiaSecondary acute myeloid leukaemia grows out of an earlier marrow disorder or follows chemotherapy or radiotherapy for another cancer. It resists standard treatment more than other leukaemias; a liposomal form of the two classic chemotherapy drugs, CPX-351, lengthens life in fit older patients, and transplant is the only route to cure.

Sezary syndromeSezary syndrome is the leukaemic form of skin lymphoma: the whole skin turns red and scaly, the lymph nodes swell, and malignant T cells circulate in the blood. It is treated to control rather than cure, with photopheresis, the antibody mogamulizumab, and drugs such as bexarotene and interferon, and a stem cell transplant is the only treatment that can cure it in fit patients.

Smouldering multiple myelomaSmouldering myeloma is myeloma that has not yet damaged bones, kidneys or blood counts. Most people are watched, but those at high risk of progressing can now be treated: the AQUILA trial showed daratumumab alone delays active myeloma, and it was approved for this use in 2025.

Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant)Splenic B-cell lymphoma/leukaemia with prominent nucleoli is the new WHO name for a rare group of B-cell leukaemias of older adults with a big spleen, large cells with obvious nucleoli and a poor response to standard treatment; it absorbs the old diagnoses B-cell prolymphocytic leukaemia and hairy cell leukaemia variant. It is treated with rituximab-based chemotherapy or newer targeted drugs.

Splenic marginal zone lymphomaSplenic marginal zone lymphoma is a slow-growing lymphoma that grows in the spleen and bone marrow, causing a very large spleen and a raised lymphocyte count but rarely swollen lymph nodes. Many people need no treatment for years; when they do, rituximab has largely replaced removal of the spleen, and hepatitis C should be treated first where it is present.

Systemic mastocytosisSystemic mastocytosis is a clonal disease of mast cells, the immune cells that release histamine; almost every case is driven by a single mutation in the KIT gene. Precise KIT-blocking pills now shrink the mast cell burden, ease symptoms and, in the aggressive forms, prolong life. Most patients have the indolent form, where the goal is controlling symptoms and preventing anaphylaxis.

T-cell large granular lymphocytic leukaemiaT-cell large granular lymphocytic leukaemia is a slow, usually non-fatal leukaemia in which a clone of cytotoxic T cells builds up in the blood and marrow and turns the immune system against the body, causing low neutrophil counts, anaemia and often rheumatoid arthritis. It is treated only when it causes problems, with low-dose immune-suppressing drugs rather than chemotherapy.

T-cell prolymphocytic leukaemiaT-cell prolymphocytic leukaemia is a rare, aggressive leukaemia of mature T cells in older adults, with a very high white cell count, a big spleen and liver, swollen nodes and sometimes skin changes. The antibody alemtuzumab given into a vein clears it in most people, but it returns within a year or two unless a stem cell transplant is done in remission.

T-cell/histiocyte-rich large B-cell lymphomaA lymphoma in which the cancer cells are a tiny minority of what the pathologist sees: scattered large B cells in a dense crowd of normal T cells and macrophages. It is a form of large B-cell lymphoma, it usually presents with disease in the liver, spleen or bone marrow, and it is easy to mistake for a different disease in both directions.

Waldenström macroglobulinaemiaA slow lymphoma that makes an abnormal IgM antibody, causing thick blood, anaemia and nerve damage. Nearly all cases share one mutation (MYD88 L265P), and BTK inhibitors control it for years.

The first 60 days

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