The Danish Myelodysplastic Syndromes Database: Patient Characteristics and Validity of Data Records

Figures & data

Table 1 Data Recorded on Five Registration Forms Used by the Danish Myelodysplastic Syndromes Database

Registration Form and Time of Registration	Variables
At diagnosis	Name, civil registration number, and demographic data
To be filled out at diagnosis	Diagnosis according to WHO(2008/2016)/ICD-10
	Date of diagnosis
	Prior hematological disease, prior chemotherapy or prior radiotherapy (yes/no/unknown)
	Results of cytogenetic evaluation (grouped according to IPSS-R)
	Cytopenia
	Anemia (< 6.2 mmol/l (yes/no)**
	Thrombocytopenia (< 100 x10^9/L) (yes/no)**
	Neutropenia (< 1.8 x10^9/L) (yes/no)**
	Blast percentage in blood and bone marrow
	Treatment with blood transfusion prior to diagnosis (yes/no/unknown)
	Presence of material in biobank (yes/no/unknown)
	Laboratory records*
Cytogenetic registration form	Date of diagnostic bone marrow sample
To be filled out at diagnosis by a clinical	Diagnoses according to WHO (2008/2016)/ICD-10
Cytogeneticist	Cytogenetic result (normal, clonal changes, not done, no mitoses)
	Cytogenetic material (peripheral blood, bone marrow, others)
	Number of analyzed metaphases, abnormal metaphases and clonal changes
	ISCN karyotype
	IPSS-R
2-year data and 5-year data	Diagnosis according to WHO (2008/2016)/ICD-10
Registration form to be filled out two and five	Date of follow-up
Years after diagnosis or in case of progression to	Treatment
AML, death or termination of outpatient follow-	Transfusion (yes/no)**
Up	Erythropoiesis-stimulating agents (yes/no)**
	Granulocyt-colony-stimulating-factors (yes/no)**
	Iron chelating agents (yes/no)**
	Hydroxyurea (yes/no)**
	Hypomethylating agents (Azacitidine) (yes/no)**
	AML-like chemotherapy (yes/no)**
	Immunosuppressive treatment (yes/no)**
	Lenalidomide (yes/no)**
	Other treatment (yes/no)**
	No treatment (yes/no)**
	Progression to acute myeloid leukemia (yes/no). If yes, date of progression
	Participation in protocol (yes/no)
	Bone marrow transplantation (yes/no). If yes, date and type
Follow up form	Status (dead/alive)
At death or termination of follow-up as an	Date of death or end of follow-up
Out-patient	Did the patient die at the hospital (yes/no)
	Was follow-up terminated from the department (yes/no)
	Referred to follow-up at another department (yes/no)

Notes: *Middle cell volume, hemoglobin, platelet count, white blood cell count, monocyte count, lactate dehydrogenase, ferritin, urate, erythropoietin, CD 34 positive cells, myoblasts, packed cell volume. **In order to register a “yes” you have to tick a “box”. If nothing is ticked off a “no” is automatically registered.

Abbreviations: AML, acute myeloid leukemia; ICD, International Classification of Diseases; ISCN, International System for Human Cytogenetic Nomenclature; IPSS-R, International Prognostic Scoring System; WHO, World Health Organization.

Table 2 Accepted Values and Gold Standards for the Validation of 48 Variables from the Danish Myelodysplastic Syndromes Database*

Variables	Correct Specification of Registered Variables	Gold Standards
Diagnosis	MDS unclassified or specification of MDS subtype	Patobank/Medical records
Date of diagnosis	Date of diagnostic bone marrow sample (± 14 days)	Patobank
Prior hematological disease (>3months)	Yes/no/unknown	Medical records
Prior chemotherapy	Yes/no/unknown	Medical records
Prior radiotherapy	Yes/no/unknown	Medical records
Anemia (< 6.2 mmol/L)	Yes/no **	Laboratory information system
Thrombocytopenia (<100 x 10^9/L)	Yes/no **	Laboratory information system
Neutropenia (<1.8 x10^9/L)	Yes/no **	Laboratory information system
Blast percentage in bone marrow	Exact value	Patobank/Medical records
Blood transfusion prior to diagnosis	Yes/no/unknown	Medical records
MCV (fL)	***	Laboratory information system
Hemoglobin (mmol/L)	***	Laboratory information system
Platelet count (10^9/L)	***	Laboratory information system
White blood cell count (10^9/L)	***	Laboratory information system
Leucocyte count (10^9/L)	***	Laboratory information system
Monocyte count (10^9/L)	***	Laboratory information system
Lactate dehydrogenase (U/L)	***	Laboratory information system
Ferritin (µg/L)	***	Laboratory information system
Transfusion	Yes/no**	Medical records
Erythropoiesis-stimulating agents	Yes/no**	Medical records
G-CSF	Yes/no**	Medical records
Iron-chelating agents	Yes/no**	Medical records
Hypomethylating agents	Yes/no**	Medical records
Hydroxurea	Yes/no**	Medical records
AML-like chemotherapy	Yes/no**	Medical records
Immunosuppresive agents	Yes/no**	Medical records
Lenalidomide	Yes/no**	Medical records
Protocol participation	Yes/no/unknown	Medical records
Progression to sAML	Yes/no/unknown	Patobank/medical records
Date of progression to sAML	Date specified (± 7 days)	Patobank/medical records
Bone marrow transplantation	Yes/no	Medical records
Date of bone marrow transplantation	Exact date of transplantation	Medical records
Type of bone marrow transplantation	Myeloablative/reduced intensity conditioning or autologous	Medical records

Notes: *Variables regarding treatment, progression to sAML, protocol participation and bone marrow transplantation were validated twice (at a registration form including 2-year data and 5-year data respectively, accounting for 30 variables in total). **In order to register a “yes” you have to tick a “box”. If nothing is ticked off a “no” is automatically registered. ***Exact value measured on day of diagnostic bone marrow sample (±30 days).

Abbreviations: G-CSF, granulocyte-colony-stimulating-factors; MCV, middle cell volume; sAML, secondary acute myeloid leukemia.

Table 3 Characteristics of Patients Registered in the Danish Myelodysplastic Syndromes Database. Data are Shown for the Whole Population, the Validation Sample and the Misclassified MDS Patients

	Total MDS Population	Validation Sample	Misclassified as MDS Patients
At diagnosis (number of patients)	2284	238	22
Male sex	1417 (62%)	131 (55%)	15 (68%)
Median age, years (IQR)	76 (68–82)	76 (68–82)	78 (63–82)
Enrolment year
2010–2014	1185 (52%)	117(49%)	16 (73%)
2015–2019	1099 (48%)	121 (51%)	6 (27%)
Diagnostic WHO subtype
MDS with single lineage dysplasia	241 (11%)	29 (12%)	–
MDS with ringed sideroblasts	238 (10%)	26 (11%)	0
MDS with excess blasts	563 (25%)	57 (24%)	0
MDS with multi-lineage dysplasia	665 (29%)	70 (29%)	-
MDS with isolated del(5q)	77 (3%)	11 (4%)	0
MDS unclassifiable	500 (22%)	46 (19%)	16 (72%)
Prior hematological disease (>3 months)	140 (6%)	19 (8%)	0
Missing	0	0	0
Unknown	59 (3%)	6 (2%)	0
Prior chemotherapy	126 (6%)	13 (5%)	0
Missing	0	0	0
Unknown	164 (7%)	14 (6%)	4 (18%)
Prior radiotherapy	96 (4%)	9 (4%)	-
Missing	0	0	0
Unknown	175 (8%)	15 (6%)	-
Blood transfusion prior to diagnosis	106 (5%)	14 (6%)	0
Missing	1218 (53%)	122 (51%)	15 (68%)
Unknown	128 (6%)	16 (7%)	-
IPSS
Good-risk	1013 (44%)	107 (45%)	12 (55%)
Intermediate-risk	746 (33%)	80 (34%)	-
Poor-risk	261 (11.5%)	22 (9%)	-
Unknown	254 (11%)	29 (12%)	-
Missing	10 (0.5%)	0	0
Anemia (hemoglobin < 6.2 mmol/L)	1353 (59%)	135 (56%)	10 (45%)
Thrombocytopenia (platelets < 100 x 10^9/L)	905 (40%)	83 (35%)	6 (27%)
Neutropenia (WBC < 1.8 x 10^9/L)	1026 (45%)	97 (41%)	11 (50%)
Blast count marrow, median (IQR)	2 (0–7)	2 (0–5)	1 (0–2)
Missing	0	0	0
Unknown	133 (6%)	6 (2.5%)	4 (18%)
MCV, fL, median (IQR)	99 (91–106)	101 (94–107)	97 (88–103)
Missing	0	0	0
Unknown	130 (6%)	8 (3%)	1 (5%)
Hemoglobin, mmol/L, median (IQR)	6.1 (5.5–6.9)	6.2 (5.5–7.0)	7 (5.6–8.2)
Missing	0	0	0
Unknown	11 (0.5%)	0	0
Platelet count, x 10^9/L, median (IQR)	125 (68–235)	140 (76.0–252)	155 (99–250)
Missing	0	0	0
Unknown	15 (0.6%)	0	0
WBC, x 10^9/L, median (IQR)	1.8 (0.9–3.5)	2.1 (1.1–3.7)	1.6 (1.1–4.2)
Missing	0	0	0
Unknown	45 (2%)	-	0
Leucocyte count, x 10^9/L, median (IQR)	3.8 (2.5–6.1)	4 (2.4–6.4)	3.9 (6.3)
Missing	0	0	0
Unknown	13 (0.6%)	-	0
Monocyte count, x 10^9/L, median (IQR)	0.3 (0.2–0.6)	0.3 (0.2–0.7)	0.7 (0.2–0.8)
Missing	1218 (53%)	122 (51%)	14 (64%)
Unknown	44 (2%)	-	0
LDH, U/L, median (IQR)*	208 (175–252)	205 (171–241)	200 (170–236)
Missing	0	0	0
Unknown	88 (4%)	9 (4%)	0
Ferritin (µg/L)	362 (174–691)	366 (186–698)	168 (79–398)
Missing	0	0	0
Unknown	331 (15%)	26 (11%)	2 (9%)
2- year data (number of patients)	1910 (84%)	197 (83%)	21 (95%)
Treatment
Transfusion	936 (49%)	100 (51%)	5 (24%)
Erythropoiesis-stimulating agents	667 (35%)	73 (37%)	4 (19%)
Granulocyte-colony-stimulating-factors	220 (12%)	22 (11%)	–
Hypomethylating agents (Azacitidine)	291 (15%)	25 (13%)	0
Iron-chelating agents	61 (3%)	7 (4%)	–
Hydroxyurea	88 (5%)	7 (4%)	–
AML-like chemotherapy	106 (6%)	12 (6%)	0
Immune suppressive agents	63 (3%)	9 (5%)	0
Lenalidomide	28 (2%)	–	0
Protocol participation	111 (5%)	6 (3%)	0
Missing	374 (16%)	0	0
Unknown	54 (2%)	5 (2%)	0
Progression to sAML	238 (13%)	31 (16%)	0
Missing	55 (3%)	5 (2.5%)	0
Unknown	40 (2%)	-	–
Date of progression to sAML	139 (58%)	21 (68%)	–
Missing	99 (42%)	10 (32%)	–
Unknown	0	0	–
Allo-HSCT	109 (5%)	17 (9%)	0
Missing	374 (16%)	0	0
Unknown	0	0	0
Date of allo-HSCT	109 (100%)	17 (100%)	–
Missing	0	0	–
Unknown	0	0	–
Type of allo-HSCT	109 (100%)	17 (100%)	–
Missing	0	0	–
Unknown	0	0	–

Notes: *For patients < 70 years old normal range for LDH is 105 to 205 U/L and for patients > 70 years normal range for LDH is 115 to 255 U/L.  - Data not shown due to small numbers.

Abbreviations: allo-HSCT, allogeneic hematopoietic stem cell transplantation; IPSS, International Prognostic Scoring System; IQR, interquartile range (25th to 75th percentiles); LDH, lactate dehydrogenase; MCV, middle cell volume; sAML, secondary acute myeloid leukemia; WBC, white blood cell count; WHO, World Health Organization.

Figure 1 Predictive values for 18 variables from the registration form completed at diagnosis from the Danish Myelodysplastic Syndromes Database. Notes: *Number of correctly coded records/number of relevant records reviewed (missing/unknown values excluded).

Abbreviations: BM, bone marrow; CI, confidence interval.

Figure 2 Predictive values for 15 variables from the registration form including 2-year data from the Danish Myelodysplastic Syndromes Database. Notes: *Number of correctly coded records/number of relevant records reviewed (missing/unknown values excluded).

Abbreviations: Allo-HSCT, allogeneic hematopoietic stem cell transplantation; CI, confidence interval, ESASs, erythropoiesis-stimulating agents; G-CSFs, granulocyte-colony-stimulating-factors; sAML, secondary acute myeloid leukemia.