Stem Cell Transplantation

First-line stem cell transplantation from related donors
compared to immunosuppressive treatment for acquired

severe aplastic anaemia (Protocol)
Kruse EB, Naumann F, Schwarzer G, Borchmann P, Peinemann F, Bohlius J, Engert A
This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane
Library 2009, Issue 3
http://www.thecochranelibrary.com
First-line stem cell transplantation from related donors compared to immunosuppressive treatment for acquired severe aplastic
anaemia (Protocol)
Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . .
ABSTRACT . . . . . . . . .
BACKGROUND . . . . . . .
OBJECTIVES . . . . . . . .
METHODS . . . . . . . . .
ACKNOWLEDGEMENTS
. . .
REFERENCES . . . . . . . .
APPENDICES . . . . . . . .
WHATS NEW . . . . . . . .
HISTORY . . . . . . . . . .
CONTRIBUTIONS OF AUTHORS
DECLARATIONS OF INTEREST .
SOURCES OF SUPPORT . . . .
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anaemia (Protocol)
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[Intervention Protocol]
First-line stem cell transplantation from related donors

compared to immunosuppressive treatment for acquired
severe aplastic anaemia
Eva-Brigitta Kruse1 , Frauke Naumann2 , Guido Schwarzer3 , Peter Borchmann4 , Frank Peinemann5 , Julia Bohlius6 , Andreas Engert6
1
Beratungszentrum fr Hygiene, Freiburg, Germany. 2 Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany.
of Medical Biometry and Statistics, German Cochrane Center, Freiburg, Germany. 4 Department I of Internal Medicine,
Center of Integrated Oncology Kln Bonn, University Hospital of Cologne, Cologne, Germany. 5 Institute for Quality and Efficiency
in Health Care, Cologne, Germany. 6 Cochrane Haematological Malignancies Group, Department I of Internal Medicine, University
Hospital of Cologne, Cologne, Germany
3 Department
Contact address: Eva-Brigitta Kruse, Beratungszentrum fr Hygiene, Sthlingerstrae 21, Freiburg, 79106, Germany.
kruse@bzh-freiburg.de. WhiteLadyofRohan@web.de. (Editorial group: Cochrane Haematological Malignancies Group.)
Cochrane Database of Systematic Reviews, Issue 3, 2009 (Status in this issue: Unchanged)
DOI: 10.1002/14651858.CD006407
This version first published online: 24 January 2007 in Issue 1, 2007. (Help document - Dates and Statuses explained)
This record should be cited as: Kruse EB, Naumann F, Schwarzer G, Borchmann P, Peinemann F, Bohlius J, Engert A. First-line stem
cell transplantation from related donors compared to immunosuppressive treatment for acquired severe aplastic anaemia. Cochrane
Database of Systematic Reviews 2007, Issue 1. Art. No.: CD006407. DOI: 10.1002/14651858.CD006407.
ABSTRACT
This is the protocol for a review and there is no abstract. The objectives are as follows:
To evaluate the effectiveness of stem cell transplantation from related donors compared to immunosuppression in the first-line treatment
of (very) severe aplastic anaemia and to assess the frequency and severity of undesired adverse effects.
anaemia (Protocol)
BACKGROUND
Description of the condition

Acquired aplastic anaemia is a rare but life-threatening disease
characterised by a failure of haemopoietic stem cells, resulting
in bone-marrow aplasia and pancytopenia. Although there are a
number of inherited forms, often associated with other symptoms
(Killick 2000), most cases are acquired forms. The incidence is
given at around 2 cases per one million inhabitants in Europe and
North America, but is usually higher in Asia and can be as much
as 15 cases per one million (Jaime-Perez 2005). Most often the
disease presents in 15 to 25-year-olds, while there is a second peak
in people older than 60 years (Brodsky 2005).
In spite of the various causes believed to lead to aplastic anaemia
- like certain drugs, chemical agents, radiation, different bacteria
and viruses as well as non-viral hepatitis and pregnancy - most cases
remain idiopathic (Killick 2000, Bacigalupo 2000). However, for
all acquired forms, the pathophysiology is probably similar: an
autoimmune destruction of haemopoietic stem cells effected by
autoreactive T cells and autoantibodies against proteins expressed
on haemopoietic cells (Young 2002, Brodsky 2005).
Patients suffering from aplastic anaemia commonly present with
signs and symptoms of thrombocytopenia, leading to various
forms of bruising and bleeding. Other manifestations of the disease
are anaemia leading to weakness, fatigue and shortness of breath,
as well as leukocytopenia. As the disease progresses, haemorrhage
and multiple severe infections due to neutropenia become more
prominent and are the most common cause of death (Brodsky
2005, Ljungman 2000). Diagnosis is established by full blood
count and bone marrow biopsy and aspirate, all of which also
serve to exclude other possible causes of aplasia and/or peripheral
pancytopenia (Marsh 2003). The following criteria determine the
presence of aplastic anaemia (Hohloch 2003, Marn-Fernandez
2000):
hypoplastic bone marrow
two out of the following three:
neutrophil count < 1x109 /l, severe aplastic anaemia: <
0,5x109 /l
thrombocyte count < 50x109 /l, severe aplastic anaemia:
< 20x109 /l
reticulocyte count < 40x109 /l, severe aplastic anaemia:
< 20x109 /l or less than 1%
These are also known as the Camitta criteria as they have been first
described by B. M. Camitta in 1975 (Camitta 1975) and little
modified since then. Special caution must be applied to differentiate aplastic anaemia from other forms of haematologic aplasia or
myelodysplastic syndromes (Hohloch 2003).
Description of the intervention
For asymptomatic aplastic anaemia, no treatment may be needed.

For all symptomatic forms, the basis of current therapy is supportive care. This includes red blood cell and platelet transfusions to
avoid complications as well as infection prevention and therapy,
sometimes iron chelation therapy and other symptomatic treatment may be necessary. Another important component is psychological support (Brodsky 2005). While this is sufficient for
patients suffering from mild forms, and up to 5% of patients
enter remission after elimination of the causative agent (MarnFernandez 2000), patients suffering from severe or very severe
aplastic anaemia need further treatment. This consists of immunosuppressive treatment and/or stem cell transplantation:
Immunosuppressive treatment. Immunosuppressive treatment is an
option available to all patients. The aim of this therapy is to prevent further loss of stem cells by suppressing the autoreactive destruction. In most patients the disease is not cured by treatment
(Brodsky 2005). Currently, the following drugs are in use: antithymocyte globulin/antilymphocyte globulin, cyclosporine A,
corticosteroids and cyclophosphamide (Waterhouse 2003, Marsh
2005). Combinations of these are common. In recent years, there
have been successful regimes of high-dose cyclophosphamide therapy without subsequent stem cell transplantation ( Brodsky 2001,
Jaime-Perez 2001, Tisdale 2000). However, these are not considered standard immunosuppressive therapy and various conditions
apply to their use.
The main advantage of immunosuppressive treatment is its availability and practicability in older patients or those without a donor.
Major drawbacks are the lack of cure and the risk of secondary
clonal disease in up to a quarter of long-term survivors (Frickhofen
2003). Still, five-year survival of 70-90% (Bacigalupo 2000, JaimePerez 2005, Schroers 2003) and fifteen-year survival of about 50%
(Viollier 2005) appear to be similar to the survival rates after transplantation from HLA-matched related donors.
Stem cell transplantation. Due to the lack of stem cells in the patient
that is part of the disease, autologous transplantation is usually not
possible in aplastic anaemia. Apart from that, it is generally not
expected to be successful because of the stem cells sensitivity to
autoimmunity. Allogeneic stem cell transplantation is a potential
cure for the disease, but requires a suitable donor and a generally
good state of health. Transplantation from matched related donors
is only available for around 30% of patients (Brodsky 2005). It is
recommended by the EBMT for patients up to 30 years without
restriction and should be considered for all patients up to 45 years
old (Ljungman 2006).
As in stem cell transplantation for other diseases, acute and chronic
graft-versus-host disease (GvHD) is the main complication of the
procedure and the main reason for treatment-related mortality (
Couriel 2004, Lee 2005). It has a strong impact on quality of life
and may well have an impact on survival, too (Brodsky 2005).
Survival at five years has been given with up to 90% (Jaime-Perez
2005, Brodsky 2005) and at 15 years, around 50% (Viollier 2005).
For patients without matched related donors, alternative donors
anaemia (Protocol)
such as matched unrelated as well as mismatched donors may be

an option, although as of now, this is not standard treatment and
survival rates compared to matched related donors are still less
favorable (Jaime-Perez 2005, Horowitz 2000).
Why it is important to do this review

Looking at these figures, it seems that overall survival after stem
cell transplantation or immunosuppressive treatment for aplastic
anaemia has been similar, in recent years at least (Bacigalupo 2000,
Viollier 2005). However, most studies on the subject contain only
registry data or small numbers of participants due to the rareness
of the disease, and age groups may be distinctly different. Given
the improved survival rates, secondary endpoints must be taken
into consideration: While both treatments are able to achieve longterm disease-free survival of around 25% at fifteen years (Viollier
2005), haematological recovery and response rates vary widely,
with figures ranging from 53% to 100% for related stem cell transplantation and 23% to 63% for immunosuppressive treatment in
recent publications (Mollee 2001, Ellis 2002, Ahn 2003). In addition, there is still some uncertainty as to which treatment offers
better quality of life and less complications.
All comparisons of the use of either first-line allogeneic stem cell

transplantation from related donors or first-line immunosuppressive therapy for treatment of aplastic anaemia will be considered.
Studies containing related and unrelated donors will be included
as long as at least 80% of donors are related donors. Studies using
bone marrow infusion instead of bone marrow transplantation will
not be included. As a stem cell source, bone marrow, peripheral
blood and cord blood will be acceptable.
There is no restriction on the drugs, mode of administration or
dose of the immunosuppressive treatment.
Types of outcome measures
Primary outcomes
Overall survival
Treatment-free survival
Secondary outcomes
Transfusion requirements/Complete and partial response

Relapse of disease
Treatment-related mortality
GvHD and graft rejection in transplanted patients
Secondary malignancies and clonal disease
Quality of life or performance status if assessed by adequate instruments, scales etc.
OBJECTIVES
To evaluate the effectiveness of stem cell transplantation from related donors compared to immunosuppression in the first-line
treatment of (very) severe aplastic anaemia and to assess the frequency and severity of undesired adverse effects.
METHODS
Criteria for considering studies for this review

Types of studies
Randomised controlled trials will be considered for this review.
Due to the nature of the intervention, studies using mendelian
randomisation based on donor availability will also be included.
Types of participants
Patients with newly diagnosed acquired (very) severe aplastic
anaemia of any cause without prior treatment for this disease will
be included. Patients with any form of constitutional anaemia
(Fanconi anaemia etc.) will not be considered. There will be no
age restriction.
Types of interventions
Search methods for identification of studies

Electronic searches
Search methods as suggested in the Cochrane Handbook for Systematic Reviews of Interventions and by the Haematological Malignancies Group will be used.
The following will be searched:
Databases:
The following electronic databases will be searched:
Ovid MEDLINE (1966 to 2006) (see Appendix 1)
Ovid EMBASE (1980 to 2006) (see Appendix 2)
The Cochrane Library Issue 2, 2006 (see Appendix 3)
Search strategies have been adapted from those suggested in the
Cochrane Handbook for Systematic Reviews of Interventions. We
did not use the RCT filter in developing the search strategy as we
suspected that the studies using mendelian randomisation might
be missed.
Conference Proceedings
Conference proceedings of relevant conferences of the following
societies will be searched for abstracts electronically:
ASH (American Society of Hematology) 2003 to 2005
EBMT (European Group for Bone and Marrow Transplantation) 2004 to 2006
anaemia (Protocol)
Electronic search in databases of ongoing trials

A number of databases and websites of relevant institutions, agencies, organisations, societies and registries will be searched for ongoing studies on the internet. A comprehensive list of those will
be available in the review.
Searching other resources
Hand search of references
References of all identified trials, relevant review articles and current treatment guidelines will be checked for further literature. A
list of those will also be available in the review.
Personal contacts
Authors of relevant studies, study groups, experts and investigators from transplantation centres worldwide who are known to be
active in the field will be contacted for unpublished material or
further information on ongoing studies.
Data collection and analysis

2. Assessment of methodological quality
3. Data extraction
4. Data analysis
Selection of studies
References obtained by the search described above will be screened
independently by two reviewers (EK, FN) using titles and abstracts. If titles and/or abstracts do not provide sufficient information to decide on the inclusion criteria stated above, full texts will
be used. Studies that pass the screening will be assessed with an
eligibility form checking the following items (details and explanations will be given on the forms used):
Is an original article or abstract of a clinical study available?
Is the study randomised or genetically randomised?
Did participants in the study suffer from acquired aplastic anaemia and what is the definition used?
Did both groups receive first-line treatment?
Did the intervention group receive stem cell transplantation from any source?
Did the control group receive immunosuppressive treatment alone?
Does the study report any of the following outcomes:
overall survival, disease-free survival, relapse, transfusion requirements, treatment-related complications,
quality of life?
To be eligible, the studies have to meet all of the above-stated
criteria. Studies including less than 5 participants per treatment
group will not be included. Full text versions of eligible studies
will be used to obtain data. Where these do not provide sufficient
information, authors will be contacted for further details.
Data extraction and management
Data from the studies will be extracted by two reviewers (EK, FN)
using a standardized data extraction form containing the following
items:
General information: author, title, source, publication
date
Study characteristics: trial design, study aims, setting,
trial dates, source of participants, inclusion/exclusion
criteria, comparability of groups, treatment allocation,
blinding, subgroup analysis, statistics, power calculations, length of follow-up
Participant characteristics: age, gender, ethnicity, number of participants recruited/allocated/evaluated, additional diagnoses, etiology, interval between diagnosis
and treatment, previous treatments, participants lost
to follow-up, number of participants in donor group
who actually received transplantation, number of participants in no-donor group who received some type of
transplantation
Interventions: setting, duration, type of conditioning/transplantation, type of immunosuppressive treatment, donor/transplant details, GVHD prophylaxis, infection prophylaxis
Outcomes: overall survival, disease-free survival, complete and partial response/transfusion requirements, relapse, treatment-related mortality, GVHD and graft
rejection, secondary malignancies and clonal disease,
quality of life
Publications reporting on more than one trial will be extracted
using one data extraction form for each trial. Trials reported in
more than one publication will be extracted on one form only.
Duplicate reports will be extracted together.
During step 1. to 3. (study selection, assessment of methodological quality, data extraction), potential disagreements between the
reviewers will be resolved by consensus. If an agreement cannot be
reached, a third reviewer will be asked to give his or her opinion.
Assessment of risk of bias in included studies
Eligible studies obtained in the process of study selection as described above will be assessed by two reviewers (EK, FN) for
methodological quality. To assess quality, a questionnaire containing the following items as suggested in the Cochrane Handbook
for Systematic Reviews of Interventions will be used (details and
explanations will be given on the forms):
Was allocation truly random (including mendelian randomisation)?
Was the treatment allocation concealed?
Were the patient characteristics at baseline similar in
both groups regarding the most important prognostic
factors?
Was the treatment masked at the outcome assessments/to data managers?
anaemia (Protocol)
Are withdrawals, drop-outs and patients lost to followup stated for each group?
Does the analysis include an ITT analysis and were less
than 10% of patients excluded in each group?
Due to the nature of mendelian randomisation, studies that meet
all criteria stated above will be checked for the following additional
criteria (details and explanations will be given on the forms used):
Were all included patients tissue-typed?
Were all patients who had a donor included in the donor
group?
Were patients without siblings excluded? If not, how
were they dealt with?
How were patients dealt with who didnt complete tissue-typing because of early death or any other reason?
Were comparable patients included in both arms?
Is the reference point for the analysis given and is the
correct analysis performed?
These criteria will be used for additional quality assessment and
possibly to perform meta-analysis.
Full text versions of eligible studies will be used to obtain data.
Where these do not provide sufficient information, authors will
be contacted for further details. Trials that do not meet the criteria of randomised allocation and allocation concealment will be
excluded to avoid selection bias. Trials that do not meet any of the
other questions will be included, but a sensitivity analysis will be
performed.
Data synthesis
For statistical analysis, data will be entered into RevMan 4.2.8.
Additional analyses not possible with RevMan will be done in the
statistical package R.
For binary outcomes, risk ratios will be calculated. For time-toevent data, hazard ratios will be calculated. A fixed effect model
will be used to calculate an overall treatment effect.
A linear regression test for publication bias will be conducted in
meta-analysis with at least four trials; a P value less than 0.1 will
be considered significant for this test. Depending on the number

of available studies, a funnel plot may be provided.
Data from studies will be presented using tables and forest plots.
Subgroup analysis and investigation of heterogeneity
The extent of heterogeneity will be assessed by the statistic I. A
result of up to 25% will be considered a low level of heterogeneity,
25 to 50% moderate and more than 50% high heterogeneity.
The following additional analyses will be performed, including
heterogeneity testing between subgroups done:
subgroup analysis:
age (children and teenagers, adults up to and
including 40 years, adults >40 years)
type of stem cell source (bone marrow, peripheral blood, cord blood)
decade of treatment (80s, 90s, 2000 and after)
Sensitivity analysis
sensitivity analysis:
quality components mentioned above, including full text publications/abstracts
ACKNOWLEDGEMENTS
Dr Sue Richards (mathematician and statistician, Oxford University, UK), Dr Keith Wheatley (mathematician and statistician,
University of Birmingham, UK) and Dr Simona Iacobelli (statistician, Universit di Roma La Sapienza, Italy) provided valuable
advice on mendelian randomisation. Dr Markus Diener (physician, Deutsches Cochrane Zentrum Freiburg, Germany) checked
the first draft and made valuable suggestions for improvement.
The editorial base of the Cochrane Haematological Malignancies
Group is funded by the German Ministry of Education and Research (BMBF).
REFERENCES
Additional references
Ahn 2003
Ahn MJ, Choi JH, Lee YY, Choi IY, Kim IS, Yoon SS, Park SY, et
al.Outcome of adult severe or very severe aplastic anemia treated with
immunosuppressive therapy compared with bone marrow transplantation: multicenter trial.. Int J Hematol 2003;78:133138.
Bacigalupo 2000
Bacigalupo A, Oneto R, Bruno B, Socie G, Passweg J, Locasciulli
A, et al.Current results of bone marrow transplantation in patients
with acquired severe aplastic anemia. Report of the European Group
for Blood and Marrow Transplantation. On behalf of the Working
Party on Severe Aplastic Anemia of the European Group for Blood

and Marrow Transplantation.. Acta Haematol 2000;103(1):1925.
Brodsky 2001
Brodsky RA, Sensenbrenner LL, Smith BD, Dorr D, Seaman PJ, Lee
SM, Karp JE, et al.Durable treatment-free remission after high-dose
cyclophosphamide therapy for previously untreated severe aplastic
anemia. Ann Intern Med 2001;135:477483.
Brodsky 2005
Brodsky RA, Jones RJ. Aplastic anaemia.. Lancet 2005;365(9471):
16471656.
anaemia (Protocol)
Camitta 1975
Camitta BM, Rappeport JM, Parkman R, Nathan DC. Selection of
patients for bone marrow transplantation in severe aplastic anemia.
Blood 1975;45:355363.
Couriel 2004
Couriel D, Caldera H, Champlin R, Komanduri K. Acute graftversus-host disease: pathophysiology, clinical manifestations, and
management. Cancer 2004;101(9):19361946.
Ellis 2002
Ellis RJ, Kahn Q, Skikne BS, Mayo MS, Allgood JW, Bodensteiner
DM, Deauna-Limayo D, Cook JD. A retrospective analysis of longterm survival in severe aplastic anemia patients treated with allogeneic
bone marrow transplantation or immunosuppressive therapy with
antithymocyte globulin and cyclosporin A at a single institution..
Mil Med 2002;167:541545.
Frickhofen 2003
Frickhofen N, Heimpel H, Kaltwasser JP, Schrezenmeier H. German Aplastic Anemia Study Group. Antithymocyte globulin with or
without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia. Blood 2003;101:12361242.
Hohloch 2003
Hohloch K, Trmper L, Schroers R. Aplastic anemia - Diagnosis
[Aplastische Anmien Diagnostik]. Dtsch Med Wochenschr 2003;
128:18381840.
Horowitz 2000
Horowitz MM. Current status of allogeneic bone marrow transplantation in acquired aplastic anemia. Semin Hematol 2000;37(1):30
42.
Jaime-Perez 2001
Jaime-Perez JC, Gonzalez-Llano O, Gomez-Almaguer D. High-dose
cyclophosphamide in the treatment of severe aplastic anemia in children. Am J Hematol 2001;66(1):71.
Jaime-Perez 2005
Jaime-Perez
JC,
Ruiz-Arguelles
GJ, Gomez-Almaguer D. Haematopoietic stem cell transplantation
to treat aplstic anaemia. Expert Opin Biol Ther 2005;5(5):617626.
Killick 2000
Killick SB, Marsh JCW. Aplatic anaemia: Management.. Blood Reviews 2000;14:157171.
Lee 2005
Lee SJ. New approaches for preventing and treating chronic graftversus-host disease. Blood 2005;105(11):42004206.
Ljungman 2000
Ljungman P. Supportive treatment of patients with severe aplastic
anemia. In: Schrezenmeier H, Bacigalupo A editor(s). Aplastic Anemia. Pathophysiology and Treatment. Cambridge: Cambridge University Press, 2000:137153.
Ljungman 2006
Ljungman P, Urbano-Ispizua A, Cavazzana-Calvo M, Demirer T,
Dini G, Einsele H, Gratwohl A, et al.Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune
disorders: Definitions and current practice in Europe. Bone Marrow
Transplant 2006;37:439449.
Marsh 2003
Marsh JCW, Ball SE, Darbyshire P, Gordon-Smith EC, Keidan AJ,
Martin A, McCann SR, Mercieca J, Oscier D, Roques AWW, Yin
JAL. Guidelines for the diagnosis and management of acquired aplastic anaemia. Br J Haematol 2003;123:782801.
Marsh 2005
Marsh JC. Management of acquired aplastic anemia. Blood Rev 2005;
19:143151.
Marn-Fernandez 2000
Marn-Fernandez P. Clinical presentation, natural course, and prognostic factors. In: Schrezenmeier H, Bacigalupo A editor(s). Aplastic Anemia. Pathophysiology and Treatment. Cambridge: Cambridge
University Press, 2000:117133.
Mollee 2001
Mollee P, Woodward N, Durrant S, Lockwood L, Gillett EA, Morton
J, Rowell J. Single institution outcomes of treatment of severe aplastic
anaemia.. Internal Medicine Journal 2001;31:337342.
Schroers 2003
Schroers R, Hohloch K, Trmper L. Aplastic anemia - Treatment
[Aplastische Anmien Therapie]. Dtsch Med Wochenschr 2003;128:
18411844.
Tisdale 2000
Tisdale JF, Dunn DE, Maciejewski J. Cyclophosphamide and other
new agents for the treatment of severe aplastic anemia. Semin Hematol
2000;37:102109.
Viollier 2005
Viollier R, Passweg J, Gregor M, Favre G, Khne T, Nissen C, Gratwohl A, Tichelli A. Quality-adjusted survival analysis shows differences in outcome after immunosuppression or bone marrow transplantation in aplastic anemia. Ann Hematol 2005;84:4755.
Waterhouse 2003
Waterhouse C, Fhrer M, Kolb H. Severe aplastic anemia [Schwere
aplastische Anmie (SAA)]. In: Hiddemann W, Haferlach T editor(s). Manual Empfehlungen zur Diagnostik, Therapie und Nachsorge Leukmien, myelodysplastische und myeloproliferative Syndrome.
Mnchen: Tumorzentrum, 2003:144152.
Young 2002
Young NS. Acquired Aplastic Anemia. Ann Intern Med 2002;136:
534546.
Indicates the major publication for the study
anaemia (Protocol)
APPENDICES
Appendix 1. MEDLINE search strategy

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40.
1 exp ANEMIA, APLASTIC/

2 (aplast$ anem$ or aplast$ anaem$).tw,kf,ot.
3 or/1-2
4 exp STEM CELL TRANSPLANTATION/
5 exp TRANSPLANTATION, HOMOLOGOUS/
6 transplant$.tw,kf,ot.
7 graft$.tw,kf,ot.
8 (allograft$ or allo-graft$).tw,kf,ot.
9 (homograft$ or homo-graft$).tw,kf,ot.
10 or/4-9
11 RANDOMIZED CONTROLLED TRIALS.sh.
12 RANDOMIZED CONTROLLED TRIAL.pt.
13 random$.tw,kf,ot.
14 CONTROLLED CLINICAL TRIAL.pt.
15 RANDOM ALLOCATION.sh.
16 DOUBLE BLIND METHOD.sh.
17 SINGLE BLIND METHOD.sh.
18 (ANIMALS NOT HUMANS).sh.
19 exp CLINICAL TRIALS/
20 CLINICAL TRIAL.pt.
21 (clin$ adj25 trial$).tw,kf,ot.
22 ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$)).tw,kf,ot.
23 PLACEBOS.sh.
24 placebo$.tw,kf,ot.
25 RESEARCH DESIGN.sh.
26 COMPARATIVE STUDY.sh.
27 exp EVALUATION STUDIES/
28 FOLLOW-UP STUDIES.sh.
29 PROSPECTIVE STUDIES.sh.
30 (control$ or prospectiv$ or volunteer$).tw,kf,ot.
31 (metaanaly$ or (meta and analy$) or (( review or search$) and (medical database$ or medline or pubmed or embase or
cochrane or systemat$))).tw,kf,ot.
META-ANALYSIS.sh.
META-ANALYSIS.pt.
exp REGISTRIES/
(registr$ or register$ or ibmtr$ or ebmt$).tw,kf,ot.
((group or regist$) and (blood or stem cell or marrow) and tranplant$ and (europ$ or international)).tw,kf,ot.
or/11-36
(ANIMALS NOT HUMANS).sh.
37 not 38
and/3,10,39
anaemia (Protocol)
Appendix 2. EMBASE search strategy

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
APLASTIC ANEMIA.sh.
(aplast$ anem$ or aplast$ anaem$).tw,hw,ot.
or/1-2
exp STEM CELL TRANSPLANTATION/
exp BONE MARROW TRANSPLANTATION/
transplant$.tw,hw,ot.
graft$.tw,hw,ot.
(allograft$ or allo-graft$).tw,hw,ot.
(homograft$ or homo-graft$).tw,hw,ot.
or/4-9
RANDOMIZED CONTROLLED TRIAL.sh.
RANDOMIZATION.sh.
random$.tw,hw,ot.
exp CLINICAL TRIAL/
(clin$ adj25 trial$).tw,hw,ot.
DOUBLE BLIND PROCEDURE.sh.
SINGLE BLIND PROCEDURE.sh.
((singl$ or doubl$ or trebl$ or tripl$)adj25 (blind$ or mask$)).tw,hw,ot.
PLACEBO.sh.
placebo$.tw,hw,ot.
FOLLOW UP.sh.
COMPARATIVE STUDY.sh.
PROSPECTIVE STUDY.sh.
(control$ or prospectiv$ or volunteer$).tw,hw,ot.
META ANALYSIS.sh.
(metaanaly$ or (meta and analy$) or ((review or search$) and (medical database$ or medline or pubmed or embase or
cochrane or sytemat$))).tw,hw,ot.
REGISTER.sh.
(registr$ or register$ or ibmtr$ or ebmt$).tw,hw,ot.
((group or regist$) and (blood or stem cell or marrow) and transplant$ and (europ$ or international)).tw,hw,ot.
or/11-29
(ANIMAL not HUMAN).sh.
30 not 31
and/3,10,32
Appendix 3. Cochrane Library search strategy

#1 MeSH descriptor Anemia, Aplastic explode all trees in MeSH products
#2 aplast* anem* OR aplast* anaem* in All Fields in all products
#3 (#1 OR #2)
#4 MeSH descriptor Stem Cell Transplantation explode all trees in MeSH products
#5 MeSH descriptor Transplantation, Homologous explode all trees in MeSH products
#6 transplant* in All Fields in all products
#7 graft* in All Fields in all products
#8 allograft* OR allo-graft* in All Fields in all products
#9 homograft* OR homo-graft* in All Fields in all products
#10 (#4 OR #5 OR #6 OR #7 OR #8 OR #9)
#11 (#3 AND #10)
anaemia (Protocol)
WHATS NEW
4 November 2008
Amended
Converted to new review version
HISTORY
Protocol first published: Issue 1, 2007
CONTRIBUTIONS OF AUTHORS
EK: development of the protocol, undertaking and screening literature searches, selecting studies, appraising quality of papers, abstracting
data from papers, analysis of data, interpretation of findings, drafting and editing of the manuscript
FN: screening literature search results, selecting studies, appraising quality of papers, abstracting data from papers, interpretation of
findings, content input
GS: providing statistical and methodological advice, analysis of data
JB: providing general advice on the review, developing search strategy, content input
FP: developing search strategy, undertaking searches for published and unpublished studies
PB: providing a clinical perspective and help with clinical questions, content input
AE: providing a clinical perspective, scientific advice, content input
DECLARATIONS OF INTEREST
Eva-Brigitta Kruse, Frauke Naumann and Julia Bohlius are members of the CHMG editorial base; Julia Bohlius is also an editor.
Guido Schwarzer is a member of the German Cochrane Centre. Frank Peinemann is a research associate at the German Institute for
Quality and Efficiency in Health Care (IQWiG). Peter Borchmann is a senior medical officer in the Department of Haematology of
the University of Cologne, Andreas Engert is coordinating editor of the CHMG and professor at the Department of Haematology of
the University of Cologne.
SOURCES OF SUPPORT
Internal sources
Cochrane Haematological Malignancies Group (CHMG), Germany.
Department of Internal Medicine I, University of Cologne, Germany.
anaemia (Protocol)
External sources
No sources of support supplied
anaemia (Protocol)
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Stem Cell Transplantation

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Stem Cell Transplantation

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First-line stem cell transplantation from related donors

compared to immunosuppressive treatment for acquired

First-line stem cell transplantation from related donors

Description of the condition

Description of the intervention

For asymptomatic aplastic anaemia, no treatment may be needed.

such as matched unrelated as well as mismatched donors may be

Why it is important to do this review

All comparisons of the use of either first-line allogeneic stem cell

Transfusion requirements/Complete and partial response

Criteria for considering studies for this review

Search methods for identification of studies

Electronic search in databases of ongoing trials

Data collection and analysis

be considered significant for this test. Depending on the number

Party on Severe Aplastic Anemia of the European Group for Blood

Indicates the major publication for the study

Appendix 1. MEDLINE search strategy

1 exp ANEMIA, APLASTIC/

Appendix 2. EMBASE search strategy

Appendix 3. Cochrane Library search strategy

Converted to new review version

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