Myeloablative Conditioning Using IV Busulphan with Post Transplant Cyclophosphamide Is Feasible

            Five patients with progressive disease were transplanted using the John’s Hopkins protocol but with IV busulphan 3.2mg/kg/day x 4 days given along with fludarabine. The donors were all siblings and the graft was peripheral blood stem cells harvested after 4 days of G-CSF.. Table I gives the details of these patients.

                                    TABLE 1 MISMATCHED RELATED HAPLO – IDENTICAL SCT

 

UPN	11/2488	13/0765	11/4498	13/2892	12/4018
Age(y)/ sex	29 / M	30 / M	26 / M	35 / M	25 / F
Diagnosis	Relapsed AML	CML - AP	CML - AP	NK Cell Lymphoma	PCL
Disease status	Progressive diseases	Progressive disease	Progressive disease	Progressive disease	Progressive disease
Donor	Sister	Brother	Brother	Brother	Brother
Age (y)/sex	33 / F	33 / M	27 / M	38 / M	32 / M
Stem cell  CD34+/kg	5.88 x 106	5.6 x 106	2.24 x 106	5.7 x 106	8.0 x 106
MNC/kg	4.33 x 108	5.3 x 108	3.46 x 108	12.4 x 108	6.72 x 108
engraftment	D+14	D +17	D +15	-	D +14
Mucositis	Gr II	Gr III/   IV	Gr I	Gr IV	Gr III
GVHD	-	Gr I			-
Stay length	47 days	38 days	27 days	36 days	28 days
D+28 chimerism	100%	100%	93%	99.9%   (11/09) 64.3%   (17/09)	99.8%
status	Alive +395	Died +60 DAH	Alive +60	Died	Alive

All patients had progressive disease and the patient with AML in first relapse with 30% blasts at the time of transplant (UPN 11/2488) is now one year post transplant with 100% donor chimerism and no graft versus host disease.. The protocol is well tolerated with rapid engraftment ( day +14-17), a very low incidence of mucositits and no VOD. One patient with CML and earlier blast transformation who had received multiple rounds of chemotherapy and was in accelerated phase at the time of transplant died of respiratory failure with a presumptive diagnosis of Diffuse Alveolar Haemorrhage which could be related to busulphan. The patient with progressive NK T cell lymphoma who had failed CHOP,  and SMILE rejected  his graft after achieving full donor chimerism and succumbed to sepsis with multi-organ failure while pancytopenic..

The addition of myelablation with IV busulphan to the John’s Hopkins protocol of PT-Cy is feasible and may reduce the frequency of relapse.