Multiple myeloma

Multiple myeloma

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Multiple myeloma NCI diagnosis treatment symptoms

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https://www.cancer.gov/types/myeloma/patient/myeloma-treatme…

Multiple myeloma is a cancer of clonal plasma cells, the antibody-producing cells in bone marrow. The cells produce a monoclonal immunoglobulin or light chain, called an M protein, which can damage bone, kidneys, marrow, and immunity. It commonly evolves through MGUS and sometimes smoldering myeloma, but neither precursor condition automatically requires treatment.

Typical clinical features: “CRAB”

Myeloma becomes clinically active when it causes one or more myeloma-defining events:

C - Hypercalcemia: thirst, constipation, nausea, confusion
R - Renal impairment: often from filtered monoclonal light chains causing cast nephropathy
A - Anemia: fatigue, pallor, dyspnea
B - Bone disease: persistent back/rib pain, lytic lesions, osteoporosis, pathological fractures, or spinal cord compression

Recurrent bacterial infections are also common because normal antibody production is suppressed. Myeloma bone disease results from increased osteoclast activity and impaired osteoblast activity, producing characteristic lytic skeletal lesions. Robbins & Kumar Basic Pathology, Multiple Myeloma section.

Diagnosis

Diagnosis usually involves:

Blood tests
- Full blood count, calcium, creatinine/eGFR, albumin, LDH
- Serum protein electrophoresis and immunofixation
- Serum free light-chain assay
- Quantitative immunoglobulins
Urine assessment
- Urine protein electrophoresis/immunofixation, often including 24-hour urine testing
Bone marrow examination
- Demonstrates clonal plasma cells
- Cytogenetic/FISH testing helps determine risk
Imaging
- Low-dose whole-body CT, PET-CT, or whole-body MRI to identify lytic lesions or focal marrow disease.

A diagnosis of active myeloma generally requires at least 10% clonal marrow plasma cells or a biopsy-proven plasmacytoma, plus a CRAB feature attributable to myeloma or a biomarker of near-term progression. Biomarkers include marrow plasma cells at least 60%, involved/uninvolved free light-chain ratio at least 100 with adequate involved light-chain level, or more than one MRI focal lesion. Goldman-Cecil Medicine, Multiple Myeloma chapter.

Management

Treatment is individualized by age, functional status, kidney function, disease risk, cytogenetics, and transplant eligibility.

MGUS and most smoldering myeloma: surveillance rather than immediate therapy.
Newly diagnosed, transplant-eligible disease: induction combination therapy, commonly involving a proteasome inhibitor, an immunomodulatory drug, dexamethasone, and often an anti-CD38 antibody; stem-cell collection followed by high-dose therapy and autologous stem-cell transplant may be used, then maintenance therapy.
Transplant-ineligible disease: continuous combination treatment adapted to frailty and comorbidities.
Relapsed/refractory disease: options include anti-CD38 antibodies, proteasome inhibitors, immunomodulatory drugs, BCMA-targeted CAR-T therapy, and bispecific antibodies such as teclistamab, depending on prior therapy and availability.

The NCI treatment summary describes treatment phases and distinguishes transplant-eligible from transplant-ineligible patients.

Supportive care

Important alongside anti-myeloma treatment:

IV fluids and urgent treatment for hypercalcemia or acute kidney injury
Bone-strengthening therapy such as a bisphosphonate or denosumab when appropriate
Pain control and radiotherapy or orthopedic/spinal management for unstable lesions
Vaccination and prompt assessment/treatment of infections
Prevention of treatment-related thrombosis when indicated
Avoidance of dehydration and nephrotoxins, particularly NSAIDs, if renal function is impaired

Seek urgent medical care for

New severe back pain, leg weakness, numbness, bowel/bladder dysfunction
Confusion, severe dehydration, or markedly reduced urine output
Fever or chills, especially during chemotherapy
Sudden fracture or rapidly worsening bone pain

Myeloma is generally treatable but is usually considered a long-term relapsing illness rather than a routinely curable one. Care should be coordinated by a hematologist-oncologist with myeloma expertise.

CML

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NCI chronic myeloid leukemia CML treatment diagnosis symptoms

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https://www.cancer.gov/types/leukemia/hp/cml-treatment-pdq

Chronic myeloid leukemia (CML)

CML is a blood and bone-marrow cancer in which the body produces excessive myeloid white blood cells. It is a myeloproliferative neoplasm driven by the BCR::ABL1 fusion gene.

Cause and molecular basis

In over 90% of cases, there is a reciprocal translocation between chromosomes 9 and 22: t(9;22). This creates the shortened chromosome 22, called the Philadelphia chromosome.

The resulting BCR-ABL1 tyrosine kinase is continuously active, causing uncontrolled proliferation and survival of myeloid cells. This molecular lesion is both diagnostic and the target of treatment. Robbins, Cotran & Kumar Pathologic Basis of Disease, CML section.

Symptoms and signs

CML is often found incidentally on a complete blood count. When symptomatic, it may cause:

Fatigue, weight loss, fever, drenching night sweats
Fullness or pain below the left ribs due to an enlarged spleen
Anemia-related symptoms
Very high white-cell count and sometimes high platelet count
In later disease, infections, bruising/bleeding, bone pain, or worsening splenic enlargement

Disease phases

CML is classified by blast percentage and clinical behavior:

Phase	Typical blast percentage	Meaning
Chronic phase	<10%	Most patients present here; generally responds very well to targeted therapy
Accelerated phase	10%-19% in the NCI description	Disease is becoming less controlled
Blast phase/crisis	≥20%	Behaves like an acute leukemia and needs urgent specialist treatment

Different classification systems use somewhat different accelerated/blast thresholds. Goldman-Cecil Medicine, CML chapter.

Diagnosis

Investigations usually include:

CBC with differential and peripheral blood smear
Bone marrow aspiration/biopsy
Cytogenetics for the Philadelphia chromosome
BCR::ABL1 testing by PCR and/or FISH
Quantitative BCR::ABL1 PCR for baseline disease burden and ongoing response monitoring

A diagnosis requires evidence of BCR::ABL1. A Philadelphia chromosome may occasionally be missed on standard cytogenetics, but FISH or PCR can still identify the fusion gene.

Treatment

The main treatment is long-term targeted therapy with a tyrosine kinase inhibitor (TKI) that inhibits BCR-ABL1:

Imatinib
Dasatinib
Nilotinib
Bosutinib
Asciminib, an allosteric BCR-ABL1 inhibitor

The individual drug choice depends on disease risk, coexisting illnesses, drug interactions, pregnancy plans, adverse-effect profiles, and mutation testing if response is inadequate.

Allogeneic stem-cell transplantation is now usually reserved for selected patients with resistant disease, certain high-risk mutations, or advanced-phase CML.

For chronic-phase CML, outcomes with modern TKIs are excellent. The NCI CML treatment guidance reports 10-year event-free and overall survival rates above 90% with available BCR-ABL1 inhibitors.

Monitoring and treatment-free remission

Response is assessed with serial quantitative BCR::ABL1 PCR testing. Some people who have taken a TKI for years and sustain a very deep molecular response may attempt supervised TKI discontinuation. This is not appropriate for everyone: relapse is common after stopping, so frequent molecular monitoring and rapid restarting of therapy when needed are essential.

Seek urgent assessment for

Fever or signs of infection
Severe fatigue, shortness of breath, bleeding, or new bruising
Marked abdominal pain/fullness from splenomegaly
New bone pain or rapidly worsening symptoms
Headache, visual symptoms, confusion, chest symptoms, or breathlessness with a markedly elevated white-cell count

CML requires hematology follow-up, but it is now commonly managed as a controllable long-term disease with oral targeted medicines.

ALL

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NCI acute lymphoblastic leukemia ALL treatment diagnosis symptoms adult childhood

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https://www.cancer.gov/types/leukemia/hp/adult-all-treatment…

Acute lymphoblastic leukemia (ALL)

ALL is an aggressive cancer of immature lymphoid cells, called lymphoblasts, in the bone marrow, blood, and sometimes lymph nodes or other organs. It can be of:

B-cell ALL: about 85% of cases, most common in children
T-cell ALL: more often affects adolescent males and can present with a mediastinal or thymic mass

Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 556.

What happens in ALL?

Leukemic blasts crowd the bone marrow and reduce normal production of:

Red cells -> anemia, fatigue, pallor, shortness of breath
Platelets -> bruising, petechiae, nose/gum bleeding
Functional white cells -> fever and recurrent infections

Leukemic cells may also infiltrate lymph nodes, liver, spleen, bone, testes, or the central nervous system.

Symptoms and signs

Common presentations include:

Fever, fatigue, night sweats, weight loss
Easy bruising, bleeding, petechiae
Bone or joint pain
Recurrent or persistent infections
Painless lymph-node enlargement
Abdominal discomfort or fullness due to liver/spleen enlargement
Headache, vomiting, cranial nerve symptoms, or seizures if there is CNS involvement
T-ALL may cause cough, breathlessness, or facial/neck swelling from a mediastinal mass.

The NCI adult ALL overview lists fatigue, fever, bleeding/bruising, shortness of breath, bone pain, lymphadenopathy, and frequent infection as typical features.

Diagnosis

The usual evaluation includes:

CBC and peripheral smear - may show blasts, anemia, thrombocytopenia, or abnormal white-cell count.
Bone marrow aspiration and biopsy - confirms acute leukemia and quantifies blasts.
Flow cytometry - determines B-cell versus T-cell lineage.
Cytogenetic and molecular tests - identify prognostic changes, including BCR::ABL1 (Philadelphia chromosome), KMT2A rearrangements, and other abnormalities.
Lumbar puncture - checks for CNS involvement, when safe and appropriate.
Minimal residual disease (MRD) testing - detects tiny amounts of leukemia after treatment and strongly informs risk-based therapy.

Treatment

ALL requires prompt care at a specialist hematology-oncology center. Treatment commonly has several phases:

Phase	Goal
Induction	Achieve complete remission using combination chemotherapy
CNS prophylaxis/treatment	Prevent or treat leukemia in brain and spinal fluid, usually with intrathecal chemotherapy and sometimes high-dose systemic therapy
Consolidation/intensification	Eliminate residual leukemia and reduce relapse risk
Maintenance	Prolonged lower-intensity therapy, particularly in many ALL protocols

For Philadelphia chromosome-positive ALL, chemotherapy is combined with a BCR-ABL1 tyrosine-kinase inhibitor such as imatinib or dasatinib. For relapsed or refractory disease, options can include blinatumomab, inotuzumab ozogamicin, CAR-T cell therapy, further chemotherapy, and selected allogeneic stem-cell transplantation. The NCI treatment guidance describes these treatment phases and options.

Prognosis

Childhood ALL is one of the most curable childhood cancers.
Adult ALL is also potentially curable, but outcomes are generally less favorable than in children.
Prognosis depends on age, initial white-cell count, B- versus T-lineage, chromosome/molecular findings, response to induction, and MRD status.

Urgent warning signs

A person with possible or known ALL should seek urgent assessment for fever, uncontrolled bleeding, breathlessness, confusion, severe headache, marked weakness, or symptoms of superior vena cava obstruction such as facial swelling or worsening shortness of breath.

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