haematologic

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 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.

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.

Burkitt 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 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 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 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.

Adding the antibody-drug conjugate gemtuzumab ozogamicin to chemotherapy lowered the chance of relapse in children with acute myeloid leukaemia. Years after the drug had been withdrawn from the US market, this trial helped bring it back for children.

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.

Erdheim-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.

Histiocytoses 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.

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.

Follicular 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.

Hairy 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 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.

People 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.

Indolent 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.

Adding the antibody rituximab to intensive chemotherapy in children with high-risk Burkitt and related lymphomas cut treatment failures by about two-thirds, making an already curable disease more so. It is the model of a joint European-North American children's cancer trial.

Intravascular 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.

Langerhans cell histiocytosis is a disorder in which a small group of immune cells with a faulty growth signal (most often a BRAF mutation) pile up in bone, skin, pituitary or organs. It ranges from a single bone lesion that heals after biopsy to a life-threatening disease of infants. A year of gentle chemotherapy cures most children, and BRAF or MEK inhibitors rescue those with resistant disease.

Lymphomatoid 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.

An 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.

Mixed-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.

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 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 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.

Nodal 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.

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 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.

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.

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 CNS lymphoma is a lymphoma confined to the brain, eyes and spinal fluid. Unlike most brain tumours it is chemo-sensitive: high-dose methotrexate-based treatment cures a substantial minority, and consolidation with a stem-cell transplant has replaced whole-brain radiation for the fit.

Primary 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 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.

Relapsed 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.

Rosai-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.

Sezary 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.

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 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 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 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 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.

A 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.