Case 77 Summary
Thanks to everyone who contributed to the case this week.
Our case started with a blood film to test our morphology skills. We picked up that the blood film showed:
- Dysplastic neutrophils
- Blasts
- NRBCs
- Tear drop poikilocytes
- Thrombocytopenia
The FBC indices identified that the patient was anaemic, thrombocytopenic and neutropenic. The initial response to these bloods should be to ensure the safety of the patient – i.e. evidence of bleeding/sepsis/ symptomatic anaemia. As a haematologist reviewing the blood film I would also look for any previous results on the system for this patient or clinic letter i.e. was he known to haematology already. Urgent discussion with GP is required if these are new findings to ensure they are aware of the results, and allow the GP to make a judgement on the clinical symptoms and whether urgent haematology review is required. If the patient is symptomatic he should be admitted to hospital urgently. However if he remains relatively stable, he could be assess as an outpatient on an urgent basis.
The next step was a bone marrow marrow biopsy. In real life we would also suggest checking haematinics/medication history/review comorbidities. We requested a coagulation screen also for this patient which I think is useful, specifically if he was bleeding, given the thrombocytopenia. A clotting may also be useful if we felt this picture may have developed due to an underlying sepsis so ensure there was no evidence of DIC.
The bone marrow showed evidence of dysplasia and 13% blast count. Previous diagnostic criteria would have classified this as RAEB-2, however WHO classification has recently been revised and the diagnosis would be MDS-EB-2
WHO classification for MDS 2016.
PB and BM findings and cytogenetics of MDS
| Name | Dysplastic lineages | Cytopenias* | Ring sideroblasts as % of marrow erythroid elements | BM and PB blasts | Cytogenetics by conventional karyotype analysis |
| MDS with single lineage dysplasia (MDS-SLD) | 1 | 1 or 2 | <15%/<5%† | BM <5%, PB <1%, no Auer rods | Any, unless fulfills all criteria for MDS with isolated del(5q) |
| MDS with multilineage dysplasia (MDS-MLD) | 2 or 3 | 1-3 | <15%/<5%† | BM <5%, PB <1%, no Auer rods | Any, unless fulfills all criteria for MDS with isolated del(5q) |
| MDS with ring sideroblasts (MDS-RS) | |||||
| MDS-RS with single lineage dysplasia (MDS-RS-SLD) | 1 | 1 or 2 | ≥15%/≥5%† | BM <5%, PB <1%, no Auer rods | Any, unless fulfills all criteria for MDS with isolated del(5q) |
| MDS-RS with multilineage dysplasia (MDS-RS-MLD) | 2 or 3 | 1-3 | ≥15%/≥5%† | BM <5%, PB <1%, no Auer rods | Any, unless fulfills all criteria for MDS with isolated del(5q) |
| MDS with isolated del(5q) | 1-3 | 1-2 | None or any | BM <5%, PB <1%, no Auer rods | del(5q) alone or with 1 additional abnormality except −7 or del(7q) |
| MDS with excess blasts (MDS-EB) | |||||
| MDS-EB-1 | 0-3 | 1-3 | None or any | BM 5%-9% or PB 2%-4%, no Auer rods | Any |
| MDS-EB-2 | 0-3 | 1-3 | None or any | BM 10%-19% or PB 5%-19% or Auer rods | Any |
| MDS, unclassifiable (MDS-U) | |||||
| with 1% blood blasts | 1-3 | 1-3 | None or any | BM <5%, PB = 1%,‡no Auer rods | Any |
| with single lineage dysplasia and pancytopenia | 1 | 3 | None or any | BM <5%, PB <1%, no Auer rods | Any |
| based on defining cytogenetic abnormality | 0 | 1-3 | <15%§ | BM <5%, PB <1%, no Auer rods | MDS-defining abnormality |
| Refractory cytopenia of childhood | 1-3 | 1-3 | None | BM <5%, PB <2% | Any |
Assessing risk
Once the patient has been diagnosed, we need to be able to assess the patients isk in order to develop an optimal management plan for that individual. Important factors to take into account are the patients age, co-morbidities and ECOG status, as these will potential affect the type of treatment appropriate for each individual patient.
IPSS-R is a decision support tool designed to assess risk of disease and therefore prognosis based on blood indices, cytogenetics, and blast count.
IPSS-R Cytogenetic risk groups*,**
| Cytogenetic prognostic subgroups | Cytogenetic abnormalities |
| Very good | -Y, del(11q) |
| Good | Normal, del(5q), del(12p), del(20q), double including del(5q) |
| Intermediate | del(7q), +8, +19, i(17q), any other single or double independent clones |
| Poor | -7, inv(3)/t(3q)/del(3q), double including -7/del(7q), Complex: 3 abnormalities |
| Very poor | Complex: >3 abnormalities |
IPSS-R Prognostic Score Values*
| Prognostic variable | 0 | 0.5 | 1 | 1.5 | 2 | 3 | 4 |
| Cytogenetics | Very Good | Good | Intermediate | Poor | Very Poor | ||
| BM Blast % | <=2 | >2-<5% | 5-10% | >10% | |||
| Hemoglobin | =>10 | 8-<10 | <8 | ||||
| Platelets | =>100 | 50-<100 | <50 | ||||
| ANC | =>0.8 | <0.8 |
IPSS-R Prognostic Risk Categories/Scores*
| RISK CATEGORY | RISK SCORE |
| Very Low | <=1.5 |
| Low | >1.5 – 3 |
| Intermediate | >3 – 4.5 |
| High | >4.5 – 6 |
| Very High | >6 |
IPSS-R: Prognostic Risk Category Clinical Outcomes*
| No. pts | Very Low | Low | Intermediate | High | Very High | |
| Patients (%) | 7012 | 19% | 38% | 20% | 13% | 10% |
| Survival*** | 8.8 | 5.3 | 3.0 | 1.6 | 0.8 | |
| AML/25%***,^ | NR | 10.8 | 3.2 | 1.4 | 0.7 | |
Somatic mutation profile was also suggested by one of our followers. This can also help provide prognostic information and risk stratification, but has not been incorporated into the IPPS-R scoring system currently. Somatic mutations in MDS driver genes especially TP53, ASXL1, DNMT3A, EZH2, and RUNX1, are associated with poorer outcomes and have been shown to add independent prognostic information. The number and types of specific mutations are strongly associated with disease outcome in MDS, and the addition of mutation data improves the prognostic value of existing risk-stratification schemes in MDS.
Approach to treatment
The patient in this case would be classified as very high risk disease given his IPSS-R score. Given his age and relative fitness, the approach of transplant should be considered. Options pre-transplant which were suggested included azacitidine, and AML – type chemo (AML 18 and AML 19 are trials currently available in the UK and would be options for this patient). Discussion with the transplant team is important early, as some patient may be consider for transplants upfront if donors were available.
References:
- The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Arber, Attilio Orazi, Robert Hasserjian, Jürgen Thiele, Michael J. Borowitz, Michelle M. Le Beau, Clara D. Bloomfield, Mario Cazzola and James W. Vardiman
Blood 2016 127:2391-2405; doi: https://doi.org/10.1182/blood-2016-03-643544
- Recent developments in myelodysplastic syndromes
Rafael Bejar and David P. Steensma
Blood 2014 124:2793-2803; doi: https://doi.org/10.1182/blood-2014-04-522136
- Revised International Prognostic Scoring System (IPSS-R) for Myelodysplastic Syndromes Risk Assessment Calculator. International working group for the prognosis of MDS. http://ipss-r.com/
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How I treat patients with myelodysplastic syndromes
