Canterbury DHB

Context

Engraftment failure

In This Section

Introduction

Engraftment and Chimerism

Approach to the Patient with Graft Failure

Management of Graft Failure

Introduction

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)*

 

12 (32)*

 

Weaver et al , 1995

Autologous, myeloma (MEL200)

18 (7-49)

 

 

22 (7-60)

Attal et al, 1996

Autologous, germ cell (cisplatin-based)

10 (7-17)

 

11 (7-27)

 

Muller et al, 2006

Autologous, int-high grade NHL (BEAM)

21 (11-49)

11 (10-31)

No G-CSF

G-CSF

 

28 (14-101)

Mills et al, 1995

Autologous, r/r HD (CBV, PBSC)

11 (4-45)

 

15 (5-69)

 

Sureda et al, 2008

Autologous, r/r HD (BEAM, CBV)

N/A

 

N/A

62 (8-1548)

Andre et al, 1999

Allogeneic

28

35

21

28

 

Allogeneic aplastic anaemia

17 (11-31)

12 (4-45)

CSA

CSA+MTX

 

22 (13-96)

22 (13-127)

Locatelli et al, 2000

Allogeneic, AML (MAC)

16 (8-24)

 

N/A

 

Vicente et al, 2007

Allogeneic, AML (RIC)

13 (8-28)

4 were >30

 

20 (7-139)

 

Oran et al, 2007

*95th centile

Engraftment and Chimerism

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.

Approach to the Patient with Graft Failure

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

  1. Detailed clinical assessment.
  2. Review drug chart and consider switching myelosuppressive drugs:
    1. Switch cotrimoxazole to pentamidine
    2. Switch ganciclovir to foscarnet or cidofovir.
  3. Consider virology testing for EBV DNA, CMV DNA, parvovirus, adenovirus, HHV6.
  4. Bone marrow aspirate and trephine (aplasia, megaloblastic, disease, haemophagocytosis?).
  5. Chimaerism studies

Management of Graft Failure

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.

About this Canterbury DHB document (116116):

Document Owner:

Andrew Butler (see Who's Who)

Issue Date:

December 2016

Next Review:

December 2018

Keywords:

Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document. Disclaimer

Topic Code: 116116