Canterbury DHB
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Engraftment is poorly understood and poorly defined. The term engraftment is often used synonymously with blood count recovery which is an unambiguous end-point and easily measured. It is usually defined as an absolute neutrophil count (ANC) ≥0.5 x 109/L for 3 consecutive days and platelets ≥20 for 7 consecutive days without platelet transfusions. Thresholds of ANC ≥1.0 x 109/L and platelets ≥50 or ≥100 x 109/L are sometimes used. There is no agreed time point at which engraftment is judged to have failed or be delayed.
The general belief is that earlier neutrophil engraftment leads to reduced transplant-related mortality and morbidity and thus improved OS, hence the rationale for the paradigm of "the more the better". Several studies have correlated the number of CD34+cells/kg with TRM and OS (Bittencourt, Blood 2002; Heimfeld, BMT 2003; Singhal, BMT 2000) although not always in the paediatric population of (Pichler, BBMT 2014). In a retrospective paediatric study, van Walraven et al did not find any instance of failed engraftment, even in patients receiving less than 1 x 108 TNC/kg (Van Walraven, BMT 2013).
Some representative studies of count recovery after autologous and allogeneic transplantation are shown below.
Type of transplant |
ANC ≥0.5 |
ANC ≥1.0 |
Platelets ≥20 |
Platelets ≥50 |
Reference |
Autologous, breast |
11 (28)* |
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12 (32)* |
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Weaver et al , 1995 |
Autologous, myeloma (MEL200) |
18 (7-49) |
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22 (7-60) |
Attal et al, 1996 |
Autologous, germ cell (cisplatin-based) |
10 (7-17) |
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11 (7-27) |
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Muller et al, 2006 |
Autologous, int-high grade NHL (BEAM) |
21 (11-49) 11 (10-31) |
No G-CSF G-CSF |
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28 (14-101) |
Mills et al, 1995 |
Autologous, r/r HD (CBV, PBSC) |
11 (4-45) |
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15 (5-69) |
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Sureda et al, 2008 |
Autologous, r/r HD (BEAM, CBV) |
N/A |
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N/A |
62 (8-1548) |
Andre et al, 1999 |
Allogeneic |
28 |
35 |
21 |
28 |
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Allogeneic aplastic anaemia |
17 (11-31) 12 (4-45) |
CSA CSA+MTX |
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22 (13-96) 22 (13-127) |
Locatelli et al, 2000 |
Allogeneic, AML (MAC) |
16 (8-24) |
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N/A |
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Vicente et al, 2007 |
Allogeneic, AML (RIC) |
13 (8-28) 4 were >30 |
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20 (7-139) |
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Oran et al, 2007 |
*95th centile
Defining graft failure after reduced-intensity and non-myeloablative conditioning is more difficult as there may not be a period of cytopenias before engraftment occurs.
In the RIC/NMA setting engraftment is better measured by chimaerism.
Definitions of complete donor chimaerism (CDC) vary between authors and publications, ranging from >95 to >99% depending on the sensitivity of the technique.
The optimal frequency of chimerism assays is debated. The ASBMT recommend analysis at 1, 3, 6 and 12 months after TCD, NMA and RIC or novel GvHD prophylaxis (Antin, 2001 #5721) with consideration to doing more frequently (every 2-4 weeks) after NMA where early chimerism patterns may predict either GvHD or graft loss.
Type of transplant |
Incidence of graft failure |
Autologous |
<1% |
Conventional myelo-ablative conditioning |
1-2% |
RIC or T-depleted MAC |
5-30% |
Consider the factors which may delay or increase the chances of failed engraftment.
Donor and conditioning |
Patient factors |
Cell dose (<1x106 CD34/kg) Female donor (allo-immunization) Older donor Bone marrow (lower CD34 %) Unrelated donor (minor HLA disparity) T-cell depletion |
Aplastic anaemia Myeloproliferative diseases Splenomegaly Reduced intensity conditioning Infection, viral Immunosuppressive drugs Ganciclovir Malnutrition |
Treat any underlying cause that is apparent after a directed examination and laboratory testing above. Other measures to consider after discussion with a transplant specialist are myeloid growth factors, manipulation of immuno-suppressive drugs, infusion of donor lymphocytes to correct mixed chimaerism, infusion of donor stem cells without prior conditioning and a second allogeneic transplant with increased intensity conditioning.
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Topic Code: 116116
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