Pentoxifylline did not prevent transplant-related toxicity in 31 consecutive allogeneic bone marrow transplant recipients.

A recent study published by Bianco et all has suggested that pentoxyifylline [3,7-dimethyl-1-(5-oxo-hexyl)-xanthine] reduces morbidity and mortality in patients undergoing bone marrow transplantation (BMT). When compared with a “good risk” control group, pentoxifylline recipients experienced less mucositis (3.7 v 18.7 days,P = .004), less hepaticvenocclusive disease (10% v 65%,P = .001), a lower incidence of renal insufficiency (3% v 65%, P = .003), and less acute graft-versus-host disease (GVHD) greater than grade I1 (35% v 68%, P = .03). Based on these encouraging results, we prophylactically administered pentoxifylline to 31 consecutive allogeneic BMT recipients (acute myeloid leukemia [AML], n = 11; acute lymphoblastic leukemia [ALL], n = 5; hybrid leukemia, n = 1; chronic myelogenous leukemia [CML], n = 10; nonHodgkin’s lymphoma [NHL], n = 2; multiple meyloma [MM], n = 2; median age, 32 years [range, 9 to 53 years]; “high risk,” 17 of 31 [55%]; “good risk,” 14 of 31 [45%]). Twenty-four patients received a transplant from an HLA-identical, MLC-negative sibling, four patients from a 1-antigen-mismatched relative, one patient from a 2-antigen-mismatched relative, and two patients from an HLA-identical, MLC-negative unrelated donor. Pentoxifylline (12 to 30 mg/kg/d by continuous infusion) was started 1 day before conditioning and switched from intravenous to oral administration at the time of discharge; it was discontinued on day 100 posttransplant. Conditioning consisted of either total body irradiation (TBI) plus cyclophosphamide and/or etoposide (n = 15) or busulfan plus cyclophosphamide and/or etoposide (n = 16). For GVHD prophylaxis, either cyclosporine A (CSA) plus short-course methotrexate (n = 22) or CSA plus methylprednisolone (n = 9) was administered. Clinical data were compared with a historical control group of 61 consecutive allogeneic BMT recipients who had undergone BMT between 1988 and 1990 (AML, n = 23, CML, n = 23; ALL, n = 8; NHL, n = 3; myelodysplasia, n = 4; median age, 30 years [range, 8 to 57 years]; “good risk,” 35 of 61 [57%]; “high risk,” 26 of 61 [43%]; donor status: HLA-identical, MLCnegative sibling, n = 57; 1-antigen-mismatched relative, n = 3; 2-antigen-mismatched relative, n = 1; conditioning: TBI plus cyclophosphamide or etoposide, n = 40; busulfan plus cyclophosphamide and/or etoposide, n = 21). Patients were analyzed for transplant-related toxicities within the first 30 days posttransplant, for day 100 survival, and for overall survival. Pentoxifylline was well tolerated at all dose levels administered and no patient experienced significant adverse side effects. Twenty-seven of 28 evaluable pentoxifylline recipients (97%) engrafted; three patients died too early to be evaluated (on days 13, 15, and 22). All 59 (100%) evaluable control patients engrafted; two patients were not evaluable (died on days 13 and 19). At 100 days posttransplant, 19 of 31 (61%) of pentoxifylline patients were alive compared with 46 of 61 (75%) of the controls. Currently, 17 of 31 pentoxifylline recipients (55%) are alive with a median follow-up of 202 days (range, 55 to 449 days) compared with 34 of 61 control patients (56%) with a median follow-up of 573 days (range, 50 to 1,576 days). Serum bilirubin levels greater than 3 mg% were observed in 20 of 31 pentoxifylline recipients (65%) and in 16 of 61 control patients (26%), respectively. Serum creatinine levels greater than 1.5 mg% were seen in 7 of 31 pentoxifylline recipients (23%) compared with 14 of 61 (23%) in the control group. Acute GVHD 11-IV developed in 22 of 31 pentoxifylline recipients (71%) (15 of 22 grade II ,3 of 22 grade 111, and 4 of 22 grade IV) and in 24 of 61 control patients (39%) (11 of 24 grade II ,9 of 24 grade 111, and 4 of 24 grade IV), respectively. Mucusitis requiring analgetic therapy developed in 21 of 31 pentoxifylline recipients (68%) compared with 21 of 61 in the control group (34%). There was no difference with regard to the days of fever greater than 38.3”C between the two groups (pentoxifylline: median, 2 [range, 0 to 111 v control: median, 2 [range, 0 to 171). Separate comparison of “standard risk” and “high risk” patients of the pentoxifylline group and the control group did not show any difference regarding transplant-related toxicities. In contrast to Bianco et al,’ who found significantly less toxicity in the pentoxifylline group, which consisted of 40% “high risk” patients even when comparing them with a “good risk” historical control group, we did not observe this advantage for our pentoxifylline patients. Our data show that, despite the parenteral prophylactic administration of pentoxifylline, substantial transplant-related toxicities were observed. To further define the value of a prophylactic use of pentoxifylline in allogeneic BMT recipients, prospective randomized trials are clearly necessary.