Gratwohl 1981.

Methods	Duration From 1976 to 1980 Randomization Allocation compatible with 'Mendelian randomization' Treatment Number of arms: 3 Type of intervention Test arm: MSD‐HSCT ("HLA‐A‐, ‐B‐, ‐Dr‐identisches, MLC‐identisches Geschwister") Control arm: IST ("kein Spender") Haploidentical family donor arm not relevant for the present review: HSCT from HLA‐matched related family members ("HLA‐haploidentisches, ABO‐kompatibles, cross match‐negatives Familienmitglied") Median follow‐up time Not reported
Participants	Setting Single‐center study Switzerland Eligibility criteria All 19 patients who had an HLA‐identical donor underwent bone marrow transplantation ("19 Patienten mit einem HLA‐identischen Geschwister erhielten eine KMT(...)") The 13 patients without an HLA‐identical donor received ALG therapy ("13 Patienten halten keinen Spender und erhielten ALG allein.") The 26 patients with a haploidentical family donor were treated with ALG and bone marrow transplantation ("26 Patienten mit einem haploidentischen, ABO‐kompatibIen, crossmatch‐negativen Familienmitglied wurden mit Antilymphozytenglobulin und KMT behandelt") Number of patients MSD‐HSCT arm: N = 19 IST arm: N = 13 Haploidentical family donor arm: N = 26 Age MSD‐HSCT arm: median 18 (range 4 to 29) years IST arm: median 23 (range 7 to 37) years Haploidentical family donor arm: median 16.5 (range 8 to 49) years Gender MSD‐HSCT arm: males 53% (10 of 19) patients IST arm: males 54% (7 of 13) patients Haploidentical family donor arm: males 81% (21 of 26) patients Further inclusion criteria to define SAA Criteria for the diagnosis of SAA fulfilled according to reference 2 of the article. ("Alle hatten SAA, erfüllten zumindest zwei der drei Blutkriterien und hatten einen mit einer SAA kompatiblen histologischen Knochenmarkbefund")
Interventions	MSD‐HSCT arm Patients received MSD‐HSCT from 1977 to 1982 Interval from diagnosis to treatment median 3.5 months (range not reported) Previous therapy: it is conceivable that the patients received blood cells and antibiotics but no specific treatment such as IST ("Von den 61 überwiesenen Patienten sind 3 trotz intensivem Zellersatz und Antibiotika gestorben, bevor die spezifische Behandlung fUr die SAA begonnen werden konnte.") Discontinuation of treatment not reported, no criteria defined Bone marrow was the stem cell source for all recipients IST arm Patients received IST from 1977 to 1982 Interval from diagnosis to treatment median 6 months (range not reported) Previous therapy: it is conceivable that the patients received blood cells and antibiotics but no specific treatment such as IST ("Von den 61 überwiesenen Patienten sind 3 trotz intensivem Zellersatz und Antibiotika gestorben, bevor die spezifische Behandlung fUr die SAA begonnen werden konnte.") Discontinuation of treatment not reported, no criteria defined 2 of the 13 included patients received a second‐line HSCT after lack of response to IST ATG: treatment details not reported Ciclosporin: no treatment Haploidentical family donor arm Patients received ALG and bone marrow transplantation from 1977 to 1982 Interval from diagnosis to treatment median 6 months (range not reported) Previous therapy: it is conceivable that the patients received blood cells and antibiotics but no specific treatment such as IST ("Von den 61 überwiesenen Patienten sind 3 trotz intensivem Zellersatz und Antibiotika gestorben, bevor die spezifische Behandlung fUr die SAA begonnen werden konnte.") Discontinuation of treatment not reported, no criteria defined
Outcomes	Primary outcome Overall survival Secondary outcomes Causes of death such as GVHD, graft failure, sepsis, hemorrhage
Notes	No competing interest reported, funding, received from non‐for profit organizations Supported in part by "Schweizerischer Nationalfond zur Förderung der wissenschaftlichen Forschung, die Schweizerische Krebsliga und das Bundesamt für Gesundheitswesen"
Risk of bias
Bias	Authors' judgement	Support for judgement
Blinding of outcome assessment (detection bias) All outcomes	High risk	Blinding of outcome assessor was not reported for any outcome
Incomplete outcome data (attrition bias) All outcomes	High risk	The data for 58 of 61 consecutively recruited patients that fulfilled the eligibility criteria have been analyzed. Therefore 3 patients have dropped out. "Von den 61 überwiesenen Patienten sind 3 trotz intensivem Zellersatz und Antibiotika gestorben, bevor die spezifische Behandlung fUr die SAA begonnen werden konnte."
Selective reporting (reporting bias)	Unclear risk	Besides overall survival, no other outcome was reported systematically
Other bias	Unclear risk	15% (2 of 13) patients assigned to the IST group had an HLA‐identical sibling donor and were actually eligible to be allocated to the MSD‐HSCT group. "13 Patienten hatten keinen Spender und erhielten ALG allein. Von diesen 13 Patienten in Gruppe C hatten 2 einen HLA‐identischen Spender". No other bias such as competing interest or cross‐over. The study was supported by non‐for‐profit institutions such as a Swiss National Research Foundation, a Swiss Cancer Association, and the Swiss Department for Health.
Comparable baseline characteristics	Low risk	There were no differences of baseline characteristics between the 2 treatment groups, in particular with reference to age. "Diese drei Gruppen sind vergleichbar bezüglich Alter, Ätiologie, vorhergehender Behandlung und Schwere der SAA bei Einweisung (Tab. 2)."
Concurrent control	Low risk	Data for the MSD‐HSCT arm were collected during the same time period as the data for the IST arm. "Dieser Bericht beschreibt alle Patienten, die dem Kantonsspital Basel zwischen Januur 1976 und Dezember 1980 wegen SAA überwiesen wurden."

Definitions of HLA‐identical or matched bone marrow vary with time and between different studies. In this table, expressions are quoted as given in the publications. Death from secondary malignancy was not considered treatment‐related mortality in the present review.

ALG: antilymphocyte globulin

ATG: antithymocyte globulin

BMT: bone marrow transplantation

G‐CSF: granulocyte colony‐stimulating factor

GVHD: graft‐versus‐host‐disease

HSCT: hematopoietic stem cell transplantation

IST: immunosuppressive therapy

MSD: matched sibling donor

MSD‐HSCT: first‐line allogeneic hematopoietic stem cell transplantation from HLA‐matched (identical) sibling donor

PMN: polymorphonuclear neutrophils

SAA: severe aplastic anemia

VSAA: very severe aplastic anemia