The value of prophylactic donor lymphocyte infusion (pDLI) is unclear and differs among diseases and transplantation protocols. Experience with this approach in patients with acute leukemia undergoing hematopoietic cell transplantation (HCT) with an alemtuzumab-incorporating conditioning protocol is lacking. We conducted a single-center prospective study to investigate the applicability and efficacy of prophylactic donor lymphocyte infusion (pDLI) in patients with leukemia undergoing HCT with a low-dose alemtuzumab-containing conditioning regimen. Inclusion criteria were high-risk acute myelogenous leukemia, acute lymphoblastic leukemia, or increasing mixed chimerism. All patients included were tapered off of immunotherapy. Exclusion criteria were a history of ≥ grade II or active graft-versus-host disease (GVHD). Of the 56 consecutive patients who underwent HCT with an alemtuzumab-containing regimen, 15 patients (8 with acute myelogenous leukemia and 7 with acute lymphoblastic leukemia) met the study inclusion criteria and received prophylactic DLI (total of 45 infusions) from 7 sibling donors and 8 unrelated donors. The first infusion was given at a median of 162 days posttransplantation. The median number of DLIs was 3, and the median cumulative CD3(+) cell dose was 2 × 10(6)cells/kg. Six of the 8 patients (75%) who received pDLI while in mixed chimerism converted to stable, complete donor chimerism. Some 47% of DLI recipients developed GVHD (4 acute GVHD and 3 with chronic GVHD) after a median cumulative dose of 2 × 10(6) CD3(+) cells/kg. After a median follow-up of 575 days, 11 (73%) pDLI recipients were alive. All 4 deaths were due to GVHD-related causes. None of the patients who received pDLIs relapsed. Patients with leukemia who received low-dose pDLI after conditioning with alemtuzumab are at low risk for relapse; however, this approach is associated with a relatively high incidence of severe GVHD.
BackgroundSacrococcygeal pilonidal disease is a chronic, well-recognized entity, characterized by the recurrent formation of an abscess or draining sinus over the sacrococcygeal area. It is one of the most common surgical problems. Rarely, chronic inflammation and recurrent disease leads to malignant transformation, most commonly to squamous cell carcinoma (SCC).Case presentationWe describe an extremely unusual case of SCC developing in a 60-year-old patient with a chronic pilonidal sinus complicated by an anal fistula. After wide surgical excision of the pilonidal sinus and fistulas and because of the poor healing process 6 months later, colonoscopy and a percutaneous fistulography were performed, revealing an anal canal-pilonidal fistula. Patient was treated with a more radical surgical resection with a prophylactic loop colostomy, but healing was not accelerated. Multiple biopsies were then taken from the surgical site at the time, which revealed the development of SCC. CT and MRI imaging techniques revealed SCC partial invasion of the coccyx and sacrum. As a result, aggressive surgical approach was decided. Histological examination revealed moderately to poorly differentiated SCC, and the patient was treated with adjuvant radiation therapy postoperatively. Nine months later, recurrence was found in the sacrum and para-aorta lymph nodes and the patient died shortly after. We discuss the clinical features, pathogenesis, treatment options, and prognosis of this rare malignant transformation.ConclusionsThe development of SCC in chronic pilonidal disease is a rare but serious complication. Symptoms are usually attributed to the sacrococcygeal pilonidal disease (SPD), and diagnosis is often made late by histological examination of biopsies. Malignant transformation should be suspected in chronic SPD with recurrent episodes of inflammation, repeated purulent discharge, poor healing, and chronic complex fistulas.
Jejunal diverticulitis is a rare entity with a higher prevalence among patients between 60 and 70 years. Jejunal diverticula are most often considered an incidental finding, but, they can have complications such as diverticulitis, perforation, abscess, generalized peritonitis, fistula, obstruction and bleeding.Setting the diagnosis still remains challenging. Physicians should be aware of their existence and the clinical suspicion should be raised, especially in the setting of acute abdominal pain where jejunal diverticulitis should be included in the differential diagnosis. A small amount of free air adjacent to the small bowel can be confusing and easily misdiagnosed as small bowel perforation, but, it can actually be found as a result of the inflammation itself without macroperforation or complications.This fact can change the therapeutic strategy to less aggressive, conservative treatments. We present a case of a patient coming to the emergency department with acute abdominal pain, signs of peritonitis, a small amount of extraluminal air, and jejunal diverticulitis without perforation was diagnosed on laparotomy, and a review of the current literature.
The optimal dose of in vivo-administrated alemtuzumab in the allogeneic transplantation setting has not been defined. We report our experience on 37 patients with high-risk diseases, mainly acute leukemia (AML 23, ALL 10 patients), who underwent sibling (49%) or unrelated (51%) PBSCT (35 patients), and received a total dose of only 10–20 mg Campath-1H as part of the conditioning, and post-transplant CYA without MTX. The neutrophil and especially the platelet engraftment were rapid. There were only two grade III–IV acute GvHD cases, which occurred in unrelated transplants in the Campath-10 cohort. Chronic GvHD developed in six cases (17%) and was limited to skin in five of them. After a median follow-up of 371 days (59–1191), 70% patients are alive and in CR (Karnofsky 100%), and 11 died (TRM n=6, relapse n=5). From the five patients relapsed, three were at advanced stage at transplant and four underwent sibling HCT with the higher (20 mg) alemtuzumab dose. With the 10 mg alemtuzumab schedule (5 mg/day at days −2 and −1) we achieve at day of transplantation low but still lymphotoxic alemtuzumab serum concentrations (176 ng/mL), whereas levels declined fast thereafter, and at engraftment nearly no Campath antibody remained in the patient's serum.
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