Decreased Acute but Not Chronic Graft Versus Host Disease (GVHD) after Allogeneic (ALLO) Hematopoietic Stem Cell Transplant (HSCT) from Matched Sibling Donors (MRD) Using Peripheral Blood Progenitor Cells (PBPC) Mobilized with Filgastrim (GCSF) Plus Dexamethasone (DEX).
Authors: Gupta Sameer , Tilden Arabella B. , Vaughan William P. , Salzman Donna E. , Lamb Lawrence S. , Katz Rhonda O. , Carabasi Matthew H. 
Published: October 2019

Controversy exists about the possibility of increased GVHD in alloMRD when PBPC are substituted for bone marrow as the transplant product because of the typically 10 fold higher T-cell dose in these products. Between 6/97 and 12/03, we performed 102 alloHSCT from MRD using PBPC mobilized with GCSF (10–16 mg/kg) and DEX 10mg/m2/day X3 (day -2 and -1 po, day 0 iv) to deplete allo reactive T-cells in vivo. All donors were apheresed on a COBE SPECTRA and cellular contents of the product were determined by flow cytometry in 98/102 cases. The donors ranged in age from 13–73, med 45. Controls consisted of 29 products collected with GCSF only mobilization from a previous trial. CD34 and CD3 were enumerated prior to ex vivo T-cell depletion with CellPro devices. The administration of DEX significantly decreased GCSF side effects with only mild steroid effects. The G-DEX mobilized grafts contained 6.55 X105 to 2.75 X107 CD34+ cells/kg of recipient (mean 8.85 X106), essentially the same yield as in the historical controls (1.01X106 to 2.47X107, mean 7.63X106), but the CD3+ yield from the G-DEX donors was 6.23X107 to 1.31X109 cells/kg recipient (mean 3.68X108) vs. 2.76X108 to 1.21X109 cells/kg of recipient (mean 6.19X108) in the controls (P=0.000001). The recipients in the study group included 49 females and 53 males aged 19–68, med 47, 51/102 HSCT were sex mis-matched, 27 female to male. Indications for HSCT included Acute Leukemia (5 ALL, 13 AML), Chronic Leukemia (18 CML, 4 CLL), Lymphoma (4 Hodgkins, 27 NHL), MDS (14), Multiple Myeloma (8) and Non-Malignant Diseases (9). GVHD prophylaxis consisted of CSA beginning on day −3 (2.5 mg/kg iv q12hr adjusted to target trough level) and methotrexate (10mg/m2 d 1 and 5mg/m2 d 3, 6, 16 and Qwky through d 100 or until onset of GVHD). Methylprednisolone was substituted for methotrexate in 7 pts and FK 506 for CSA for toxicity in 9 pts at some point in their course. With follow up for survivors from 6–84 mo (med 34), the cumulative probability of developing grade II-IV and III-IV aGVHD was 19.9% and 13.1% respectively. However, extensive cGVHD occurred in 39 patients (cumulative probability 62.4%). cGVHD was progressive from aGVHD in 10 cases, 8 of whom died of GVHD or immunodeficiency. The remaining 29 pts had de novo (21) or interrupted (8) cGVHD, but 19 of the de novo and 5 of the interrupted cases occurred during or shortly after discontinuing GVHD prophylaxis or treatment respectively. Of these 29 pt, 1 died of recurrent disease but of the remaining 28, 15 (53.6%) were alive at last follow up (12 De Novo, 3 Interrupted) and 7 have had resolution of their GVHD (5 De Novo, 2 Interrupted). Despite achieving only a modest reduction in CD3+ graft content, the G-DEX mobilized products appeared to cause less than expected aGVHD, but the cGVHD risk remains high. The fact that the majority of cGVHD occurred during or immediately after tapering prophylaxis or treatment for aGVHD and often had an aGVHD type presentation suggests that in vivo modification with DEX may only delay the onset of aGVHD. Alternate prophylactic strategies or longer taper of current standard GVHD prophylaxis is needed.