• Patient reported outcome measures (PROM) via approved quality of life questionnaires. [ Time Frame: Duration of study (5 years) ]
  Analysis of approved questionnaires: EORTC CLL17
• To study other clinically significant events, not inevitably due to disease progression in this patient cohort [ Time Frame: Duration of study (5 years) ]
  Assessed by analysing suspected unexpected serious adverse reactions (SUSARs) reported
• Production of evidence-based standard of care guidelines for the monitoring and follow-up of patients with these pre-cancerous conditions [ Time Frame: Duration of study (5 years) ]
  The identification of relevant markers can be used to create guidelines for optimal monitoring of patients with these pre-cancerous conditions
• Patient reported outcome measures (PROM) via approved quality of life questionnaires. [ Time Frame: Duration of study (5 years) ]
  Analysis of approved questionnaires: EORTC NHL-LG20
• Patient reported outcome measures (PROM) via approved quality of life questionnaires. [ Time Frame: Duration of study (5 years) ]
  Analysis of approved questionnaires: EORTC QLQ-C30
• Patient reported outcome measures (PROM) via approved quality of life questionnaires. [ Time Frame: Duration of study (5 years) ]
  Analysis of approved questionnaires: EORTC QLQ-MY20

The purpose of the study is to monitor patients with early stage lymphoproliferative disorders not meeting criteria for treatment, including early stage Chronic Lymphocytic Leukaemia (CLL), Monoclonal B-cell Lymphocytosis (MBL), Monoclonal Gammopathy of Uncertain Significance (MGUS), asymptomatic Waldenstroms Macroglobulinaemia (WM) and Smouldering Myeloma (SM).

Each of these disorders has a pre-cancerous phase when abnormalities can be seen in the blood, however treatment may not be required. A minority of people with early stage lymphoproliferative disorders will go on to need treatment for blood or bone marrow cancer.

Currently the investigators do not have a reliable way to predict which of these individuals with these disorders are more likely to develop a blood or bone marrow cancer. By studying a large group of individuals over time we hope to discover more about what factors might predict progression.The investigators may be able to identify markers which identify individuals who are more or less likely to develop blood or bone marrow cancer. These markers might be particular symptoms, gene changes called mutations or levels of particular molecules or cells in the blood or bone marrow. In the longer term this may enable us to identify those people who would benefit from certain types of treatment or from receiving treatment at an earlier stage and also to confidently reassure those who will never progress.

Patients will be studied for up to 5 years with blood, bone marrow and saliva samples taken at key time-points to help answer these questions. In addition to looking for these markers we will also collect information about:

• What it is like to live with one of these conditions
• How many people with these conditions develop other significant medical conditions, such as serious infections, thrombosis (blood clots) or other types of cancer.

• Cohort 1
  Participants with Monoclonal B-Cell Lymphocytosis or Asymptomatic Chronic Lymphocytic Leukaemia
• Cohort 2
  Participants with IgM Monoclonal Gammopathy or Asymptomatic Waldenstrom's Macroglobulinaemia
• Cohort 3
  Participants with IgA or IgG Monoclonal Gammopathy or Smouldering Myeloma

Inclusion Criteria:

1. Patients diagnosed within the previous three years with one of the following:

   1. High count monoclonal B-cell lymphocytosis (MBL) i.e. clonal B-cell population 0.5-4.9 109/L
   2. Rai Stage 0-2/ Binet Stage A or Stage B Chronic Lymphocytic Leukaemia not meeting the IWCLL criteria for treatment
   3. IgG or IgA Monoclonal Gammopathy of Uncertain Significance meeting one of the following criteria:

   i) IgA paraprotein >10g/L or

   ii) IgG paraprotein >15g/L or

   iii) IgA/IgG paraprotein below these cut-offs but kappa:lambda light chain ratio of

   • <0.1 to >3.0 (For OUH participants or sites with no pre-defined cut offs for high risk MGUS) or
   • within the cut off criteria of the local laboratory ranges for high risk MGUS

   iv) Patients not meeting the cut-offs defined in points i) to iii) but who are referred to secondary care e.g. due to general practitioner (GP) concern or for investigation of symptoms

   d. IgM Monoclonal Gammopathy of Uncertain Significance meeting one of the following criteria: i) IgM paraprotein >10g/L or

   ii) IgM paraprotein <10g/L and difference between the kappa and lambda light chains of >50mg/L

   iii) Patients not meeting the cut-offs defined in point i) and ii) but who are referred to secondary care e.g. due to GP concern or investigation of symptoms

   e) Asymptomatic smouldering Waldenstrom's Macroglobulinaemia not meeting the criteria for treatment f) Smouldering myeloma not meeting the criteria for treatment

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
3. Age 16 years and over
4. Sign written informed consent
5. The patient is willing and able to comply with the protocol for the duration of the study and scheduled follow-up visits and examinations

Exclusion Criteria:

1. Pregnant or breast-feeding women. Pregnant or breast-feeding women may be re-screened following delivery and/or cessation of breastfeeding, as appropriate
2. Previous chemotherapy or immunotherapy for any haematological cancers
3. Treatment with any other investigational agent, or participation in an interventional clinical trial within 28 days prior to enrolment.
4. Patients in cohort 2 or 3 on anticoagulation for a diagnosis of pulmonary embolus or deep vein thrombosis within the last 3 months or with a mechanical heart valve or any other condition causing a significant risk of thromboembolism. Participants who are anticoagulated for atrial fibrillation are eligible, but will be asked to interrupt anticoagulation 3 days prior to bone marrow examination
5. Other psychological, social or medical condition, physical examination finding or laboratory abnormality that the investigator considers would make the patient a poor study candidate or could interfere with protocol compliance or the interpretation of study results.
6. Any other malignancy that requires active surgical or chemotherapeutic Patients on long term hormone therapies (e.g. Tamoxifen) are permitted to enrol at the discretion of investigator, after considering the overall clinical context
7. Any significant concurrent medical resulting in life-expectancy (including but no limited to renal, Hepatic, haematological gastrointestinal, endocrine pulmonary neurological, cerebral or psychiatric disease
8. For cohort 3: Any contraindication for MRI- presence of any metallic foreign body, eGFR <30 and allergy to gadolinium contrast