The first 60 days: Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms
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. Below, week by week, is what OnCo's record of Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- Medical oncologistNamed in the standard of care for: Higher-risk CMML, fit with a donor, Higher-risk or symptomatic CMML, not transplant candidate, Proliferative CMML with symptomatic leucocytosis or splenomegaly, Juvenile myelomonocytic leukaemia.
- Transplant and cell therapy teamNamed in the standard of care for: Higher-risk CMML, fit with a donor, Proliferative CMML with symptomatic leucocytosis or splenomegaly, Juvenile myelomonocytic leukaemia.
- Palliative and supportive care teamNamed in the standard of care for: Higher-risk or symptomatic CMML, not transplant candidate.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
- 1.Higher-risk CMML, fit with a donorNCCN category Category 2A, NCCN Guidelines: Myelodysplastic Syndromes (CMML section); EHA/ELN CMML recommendations
Allogeneic haematopoietic stem cell transplant, often after hypomethylating-agent cytoreduction; the only curative option.
- 2.Higher-risk or symptomatic CMML, not transplant candidateNCCN category Category 2A, NCCN Guidelines: MDS (CMML)
Azacitidine or decitabine (or oral decitabine-cedazuridine) until progression; supportive care with transfusion and growth factors.
- 3.Proliferative CMML with symptomatic leucocytosis or splenomegalyWattel et al., Blood 1996 (hydroxyurea vs etoposide)
Hydroxyurea (superior to etoposide in the randomised GFM trial); ruxolitinib in trials for symptomatic proliferative disease.
Allogeneic transplant; azacitidine as bridging therapy (EMA approval 2019 for JMML); watchful waiting for some CBL- or Noonan-associated cases that regress spontaneously.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Monocyte count and percentage; flow cytometric monocyte subset partitioning, Bone marrow blasts and dysplasia, Cytogenetics, complex), NGS: TET2, SRSF2, ASXL1, RUNX1, SETBP1, NRAS, KRAS, CBL, JAK2, SF3B1; exclusion of BCR-ABL1 and PDGFRA/B rearrangements, CPSS and CPSS-Mol risk score), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include CMML, dysplastic type, CMML, proliferative type, CMML-1 and CMML-2 by blast percentage.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Higher-risk CMML, fit with a donor
- For my situation (higher-risk cmml, fit with a donor), which of the standard options do you recommend and why?Guideline options include: Allogeneic haematopoietic stem cell transplant, often after hypomethylating-agent cytoreduction; the only curative option.
- Am I a candidate for Azacitidine, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Higher-risk or symptomatic CMML, not transplant candidate
- For my situation (higher-risk or symptomatic cmml, not transplant candidate), which of the standard options do you recommend and why?Guideline options include: Azacitidine or decitabine (or oral decitabine-cedazuridine) until progression; supportive care with transfusion and growth factors.
- Am I a candidate for Azacitidine, Decitabine + cedazuridine (oral), and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Proliferative CMML with symptomatic leucocytosis or splenomegaly
- For my situation (proliferative cmml with symptomatic leucocytosis or splenomegaly), which of the standard options do you recommend and why?Guideline options include: Hydroxyurea (superior to etoposide in the randomised GFM trial); ruxolitinib in trials for symptomatic proliferative disease.
- Am I a candidate for Hydroxyurea (hydroxycarbamide), Ruxolitinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Juvenile myelomonocytic leukaemia
- For my situation (juvenile myelomonocytic leukaemia), which of the standard options do you recommend and why?Guideline options include: Allogeneic transplant; azacitidine as bridging therapy (EMA approval 2019 for JMML); watchful waiting for some CBL- or Noonan-associated cases that regress spontaneously.
- Am I a candidate for Azacitidine, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Ruxolitinib, Venetoclax, Azacitidine, Allogeneic stem cell transplantation?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “No drug alters the disease course; RAS-pathway inhibitors, GM-CSF antibodies and venetoclax combinations are in early trials”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Transformation to AML in a substantial minority; sequential mutation tracking to intervene earlier is being studied”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- A Multi-phase Study of ASTX030 (Azacitidine and Cedazuridine) in Myeloid Neoplasm Alone or in Combination With Venetoclax in AML (AZTOUND Study)Phase 2/3 · recruiting · NCT04256317A Multi-phase, Pharmacokinetics, Safety, and Efficacy Study of ASTX030 (Azacitidine and Cedazuridine) as Monotherapy in Subjects With Myeloid Neoplasm or in Combination With Venetoclax in Subjects With AML (AZTOUND Study)
- Pacritinib vs. Hydroxyurea in Advanced Proliferative Chronic Myelomonocytic LeukemiaPhase 2 · recruiting · NCT07033598A Randomized Phase 2 Study of Pacritinib vs. Hydroxyurea in Patients With Advanced Proliferative Chronic Myelomonocytic Leukemia
- A Study of CFI-400945 With or Without Azacitidine in Patients With AML, MDS or CMMLPhase 1/2 · active · NCT04730258Phase 1b/2 Clinical Study of the Safety, Tolerability, and Pharmacokinetic and Pharmacodynamic Profiles of CFI-400945 as a Single Agent or in Combination With Azacitidine in Patients With AML, MDS or CMML
- A Study to Assess Safety, Tolerability and Preliminary Efficacy of Bexmarilimab in Combination With Standard of Care in Patients With Hematological MalignanciesPhase 1/2 · active · NCT05428969A Phase I/II Open-Label Study to Assess the Safety, Tolerability and Preliminary Efficacy of the Clever-1 Antibody Bexmarilimab in Combination With Standard of Care Therapy in Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia or Acute Myeloid Leukemia
- Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tuspetinib (HM43239) in Patients With Relapsed or Refractory Acute Myeloid LeukemiaPhase 1/2 · recruiting · NCT03850574A Phase 1/2 Open Label, Multicenter, Dose Escalation and Expansion Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM43239 in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms: the full pageChronic 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.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Conditioning regimen (myeloablative, reduced-intensity): The chemotherapy (with or without whole-body radiation) given in the days before a stem cell transplant to destroy the diseased marrow and, for donor transplants, suppress the patient's immune system so the graft is not rejected.
- Hypomethylating agents (azacitidine, decitabine): Low-intensity chemotherapy that strips chemical 'off' switches (methyl groups) from DNA so silenced genes can be read again.
- Cytopenias and myelosuppression: The umbrella term for low blood counts of any kind (white cells, red cells, platelets) when treatment suppresses the bone marrow.
- Blasts (leukaemic blast cells): Immature blood cells that should mature in the marrow but in acute leukaemia multiply without growing up.
- Cytogenetics and karyotype: Looking at a cancer's chromosomes under the microscope to find missing, extra, broken or swapped pieces.
Every term links to the glossary.