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Haematological Malignancies
Conditioning Therapy regimen.
58
The reduced relapse rate is hampered by an increase in the
Traditionally, conditioning therapy including total body irradiation (TBI) non-relapse mortality and morbidity in long-term survivors, with
has been associated with better DFS for ALL patients,
14,56
especially in severely impaired quality of life for patients presenting with the
children.
57
Busulfan-containing regimens have been associated with a extensive form of the disease. Consequently, the GvL effect has been
higher TRM (basically hepatic sinusoidal obstructive syndrome and mostly evident in the limited type of chronic GvHD. This GvL effect of
haemorrhagic cystitis).
58
The higher relapse rate associated with chronic GvHD has been pointed out as stronger for ALL patients with
chemotherapy conditioning has not been confirmed by all groups.
9
translocations (including Phi
+
ALL)
22,64
or normal diploid cytogenetics
There are no randomised studies comparing different conditioning than for patients with deletions or numeric abnormalities.
22
The
therapies specifically for ALL. Some comparative studies included only a presence of acute GvHD also had a positive impact in decreasing
variable proportion of ALL patients and most were performed in the the relapse rate,
14,25,33
but it is associated with a higher TRM and a
matched-sibling setting. Moreover, none of these comparative studies decreased survival if it is severe.
13,14
As the disease status at transplant
performed busulfan adjustment based on the drug plasma levels. Non- and the presence of chronic GvHD are the main factors influencing
myeloablative conditioning regimens allow transplantation to be relapse in adult patients with high-risk ALL after an unrelated
performed in patients who are not candidates for myeloablative transplant,
22
the lower incidence of GvHD found in UCB-SCT could
therapies due to advanced age, co-morbidities or a previous justify the trend for a higher relapse rate in patients receiving unrelated
myeloablative SCT. With this approach a graft-versus-leukaemia (GvL) cord blood as the source of haematopoietic stem cells.
effect may be obtained with acceptable toxicity in the related and
unrelated settings.
52,59,60
The high incidence of disease relapse remains Conclusions
the main drawback of such an approach. Disease status at transplant An alternative donor SCT should be considered for poor-prognosis adult
and the presence of chronic GvHD are other main factors influencing ALL patients in first CR without a sibling donor. However, all unrelated
relapse in this setting. However, for adults with ALL in first CR, reduced- transplant modalities are associated with high TRM. The disease status
intensity conditioning (RIC) allografting results in a promising DFS with at transplant and the presence of GvHD are the main factors influencing
acceptable TRM. In some groups, SCT with RIC has been followed by a relapse in adult patients with high-risk ALL after an unrelated transplant.
double or multiple graft for UCB-SCT, a procedure that seems to be A clear recommendation about which is the best conditioning therapy or
associated with a slightly higher incidence of GvHD and a possible even the best unrelated source does not exist. The particularities of
improvement of the GvL effect.
61
In vivo T-cell depletion is the most patients, progenitor compatibility and cellularity (if unrelated cord blood
effective method for preventing GvHD after alloSCT, and in spite of a progenitors) should be carefully considered prior to transplant. Finally,
delayed immunological reconstitution this effect could decrease the the time interval to obtain the unrelated haematopoietic progenitors
TRM in USCT.
62
In addition, the T-cell depletion of the graft has been should also be taken into account in the selection process. ■
associated with a higher incidence of CMV and fungal infection in the
unrelated bone marrow setting, and as thymoglobulin is commonly
Christelle Ferrà is an Attending Physician in the Haematology Department at the
given as conditioning therapy for UCB-SCT patients, this could
Catalan Institute of Oncology, University Hospital Germans Trias i Pujol in Badalona.
contribute to a high incidence of infections in UCB-SCT. On the other She is a member of the Spanish Society of Hematology and the European Group for
hand, as T-cell depletion could also contribute to relapse, this procedure
Blood and Marrow Transplantation. Dr Ferrà was licensed in medicine in 1988 at the
Universitat Autònoma de Barcelona and became a specialist in haematology in 1992.
is not routinely performed in high-risk ALL patients.
She received her doctorate in medicine in 1996.
Graft-versus-leukaemia Effect
Josep-Maria Ribera is Chief of the Haematology Department and Director of the Stem
In ALL, the antileukaemic activity of GvHD has been traditionally
Cell Transplantation Unit at the Catalan Institute of Oncology, University Hospital
considered weaker than for other haematological diseases. However,
Germans Trias i Pujol in Badalona, and a Profesor of Medicine-Haematology at the
Autonomous University of Barcelona. Dr Ribera is also Chairman of the trials of acute
many authors
12,22,24,61–64
have demonstrated the antileukaemic effect of
lymphoblastic leukaemia in the PETHEMA (Programa de Estudio y Tratamiento de las
chronic GvHD, either in children
65,66
or in adult patients receiving a
Hemopatías Malignas) Group of the Spanish Society of Hematology.
related or especially an USCT, either with a myeloablative or RIC
1. Bishop MR, Logan BR, Gandham S, et al., Long-term hematopoietic stem cell transplantation as part of transplants for adult acute lymphoblastic leukaemia: a
outcomes of adults with acute lymphoblastic leukemia postremission therapy improves survival for adult patients comparison of the three major options, Bone Marrow
after autologous or unrelated donor bone marrow with high-risk acute lymphoblastic leukemia: a Transplant, 2006;38:467–75.
transplantation: a comparative analysis by the National metaanalysis, Cancer, 2006;106:2657–63. 10. Cornelissen JJ, Van der Holt B, Verhoef GEG, et al.,
Marrow Donor Program and Center for International Blood 5. Hunault M, Harousseau JL, Delain M, et al., Better outcome Myeloablative allogeneic versus autologous stem cell
and Marrow Transplant Research, Bone Marrow Transplant, of adult acute lymphoblastic leukemia after early transplantation in adult patients with acute lymphoblastic
2007;41:635–42. genoidentical allogeneic bone marrow transplantation leukemia in first remission: a prospective sibling donor
2. Goldstone AH, Richards SM, Lazarus HM, et al., In adults (BMT) than after late high-dose therapy and autologous versus no donor comparison, Blood, 2009;113:1375–82.
with standard-risk acute lymphoblastic leukemia, the BMT: a GOELAMS trial, Blood, 2004;104:3028–37. 11. Hoelzer D, Göckbuget N. New approaches in acute
greatest benefit is achieved from a matched sibling 6. Thiebault A, Vernant JP, Degos L, et al., Adult acute lymphoblastic leukemia in adults. Where do we go?,
allogeneic transplantation in first complete remission, and lymphocytic leukemia study testing chemotherapy, and Semin Oncol, 2000;27:540–59.
an autologous transplantation is less effective than autologous and allogeneic transplantation. Follow-up 12. Cornelissen JJ, Carston M, Kollman C, et al., Unrelated
conventional consolidation/mainte-nance chemotherapy in reports of the French protocol LALA 87, Hematol Oncol Clin marrow transplantation for adult patients with poor-risk
all patients: final results of the International ALL Trial (MRC North Am, 2000;14:1353–66. acute lymphoblastic leukemia: strong graft-versus-leukemia
UKALL XII/ECOG E2993), Blood, 2008;111:1827–33. 7. Thomas X, Boiron JM, Huguet F, et al., Outcome of effect and risk factors determining outcome, Blood,
3. Ribera JM, Oriol A, Bethencourt C, et al., Comparison of treatment of adults with acute lymphoblastic leukemia: 2001;97:1572–7.
intensive chemotherapy, allogeneic or autologous stem cell analysis of LAL-94 trial, J Clin Oncol, 2004;22:4075–86. 13. Chim CS, Lie AKW, Liang R, et al., Long-term results of
transplantation as post-remission treatment for adult 8. Hallböök H, Hägglund H, Stockelberg D, et al., Autologous allogeneic bone marrow transplantation for 108 adult
patients with high-risk acute lymphoblastic leukemia. and allogeneic stem cell transplantation in adult ALL: the patients with acute lymphoblastic leukemia: favourable
Results of the PETHEMA ALL-93 trial, Haematologica, 2005; Swedish Adult ALL Group experience, Bone Marrow Transplant, outcome with BMT at first remission and HLA-matched
90:1346–56. 2005;35:1141–8. related donor, Bone Marrow Transplant, 2007;40:339–47.
4. Yanada M, Matsuo K, Suzuki T, Naoe T, Allogeneic 9. Marks DI, Aversa F, Lazarus HM, Alternative donor 14. Kiehl MG, Kraut L, Schwerdfeger R, et al., Outcome of
48 EUROPEAN HAEMATOLOGY
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