Occurrence of graft-versus-host disease increases mortality after umbilical cord blood transplantation for acute myeloid leukaemia: a report from Eurocord and the ALWP of the EBMT.

BACKGROUND: The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukaemia (AML) relies on immune-mediated graft-versus-leukaemia effects. Previous studies have suggested a strong association between graft-versus-host disease (GVHD) occurrence and graft-versus-leukaemia effects after allogeneic hematopoietic cell transplantation. METHODS: Here, we evaluated the kinetics of relapse rate in correlation with GVHD occurrence after UCBT. The kinetics of relapse rate over time in correlation to GVHD occurrence were assessed by calculating the relapse rate per patient-year within sequential 90-day intervals. The impact of GVHD on relapse and mortality was further studied in multivariate Cox models handling GVHD as a time-dependent covariate. RESULTS: The study included data from 1068 patients given single (n = 567) or double (n = 501) UCBT. The proportion of patients with grade II, III and IV acute GVHD was 20%, 7% and 4%, respectively. At 2 years, the cumulative incidence of chronic GVHD was 42%, the cumulative incidence of relapse was 32%, and overall survival was 32% as well. Relapse rates declined gradually over time during the first 30 months after transplantation. There was a possible suggestion that grade II-IV acute (HR = 0.8, P = 0.1) and chronic (HR = 0.65, P = 0.1) GVHD decreased relapse risk. However, grade II-IV acute GVHD significantly increased early (the first 18 months after UCBT) mortality (HR = 1.3, P = 0.02), whilst chronic GVHD increased each early (HR = 2.7, P < 0.001) and late (HR = 4.9, P < 0.001) mortality after UCBT. CONCLUSIONS: The occurrence of grade II-IV acute or chronic GVHD each increases overall mortality after UCBT for AML mitigating the possible graft-versus-leukemia effect of GVHD.

Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia.

Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared outcomes after UCBT and Haplo in adults with de novo acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Median follow-up was 24 months. Analysis was performed separately for patients with AML, n=918 (Haplo=360, UCBT=558) and ALL, n=528 (Haplo=158 and UCBT=370). UCBT was associated with delayed engraftment and higher graft failure in both AML and ALL recipients. In multivariate analysis, UCBT was associated with lower incidence of chronic graft-vs-host disease both in the AML group (hazard ratio (HR)=0.63, P=0.008) and in the ALL group (HR=0.58, P=0.01). Not statistically significant differences were observed between Haplo and UCBT for relapse incidence (HR=0.95, P=0.76 for AML and HR=0.82, P=0.31 for ALL), non-relapse mortality (HR=1.16, P=0.47 for AML and HR=1.23, P=0.23 for ALL) and leukemia-free survival (HR 0.78, P=0.78 for AML and HR=1.00, P=0.84 for ALL). There were no statistically differences on main outcomes after unmanipulated Haplo and UCBT, and both approaches are valid for acute leukemia patients lacking a HLA matched donor. Both strategies expand the donor pool for patients in need.

Is leishmaniasis an "unusual suspect" of infection in allogeneic transplantation?

Leishmaniasis is a disease of the immunocompetent population, more often affecting infants and young children. However, the number of leishmaniasis cases associated with immunosuppression has increased over the last 20 years. The visceral form of the disease, visceral leishmaniasis (VL), is identified as an opportunistic infection in immunosuppressed individuals, occurring mainly after solid organ transplantation, especially in renal transplant recipients. Limited data are available about VL after hematopoietic stem cell transplantation (HSCT). We report the cases of 3 patients with late VL after allogeneic HSCT, and review the literature.

Specific abnormalities versus number of abnormalities and cytogenetic scoring systems for outcome prediction after allogeneic hematopoietic SCT for myelodysplastic syndromes.

Newer cytogenetic scoring systems for myelodysplastic syndromes (MDSs), like cytogenetic stratification of the revised international prognostic scoring system (IPSS-R) or monosomal karyotype, may also improve outcome prediction after hematopoietic SCT (HCT). We compared the prognostic value of specific cytogenetic abnormalities, IPSS-R karyotype and monosomal karyotype for HCT outcome in 98 patients with MDS and AML post MDS. Higher-risk IPSS-R karyotype, 3q21q26 and transformation to AML before HCT were associated with increased cumulative incidence of relapse (CIR), whereas OS was adversely influenced by del 5q/-5, abnormalities of chromosomes 11 and 17 and cytogenetic IPSS-R very poor category. Karyotype with ⩽2 abnormalities and no abnormalities of chromosomes 3, 5, 7, 11 and 17 was an independent prognostic factor of lower CIR (hazard ratio (HR)=0.2, P=0.01) and longer OS (HR=0.5, P=0.03). In conclusion, some specific cytogenetic abnormalities and high cytogenetic complexity, as reflected by IPSS-R very poor karyotype, rather than monosomal karyotype, were associated with higher CIR and shorter OS after HCT. Conversely, results were encouraging in patients lacking those abnormalities, who may be very good candidates for HCT.

Identification of prognostic factors predicting outcome in Hodgkin's lymphoma patients relapsing after autologous stem cell transplantation.

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT. METHODS: Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed. RESULTS: Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure. CONCLUSION(S): Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.

Solitary fibrous tumor of the tongue: case report and literature review.

Solitary fibrous tumor (SFT) is an uncommon spindle cell neoplasm with unpredictable behavior. It was originally described in the pleura, but is now known to occur in various locations. SFT of the tongue is rare, with only four cases on record. An SFT of the anterolateral part of the left side of the tongue, which occurred in a 48 year-old man is recorded. The tumor was resected and the patient remains free of recurrence 3 years postoperatively.

Constitutional pericentric inversion of chromosome 9 and hematopoietic recovery after allogeneic stem cell transplantation.

Recent reports suggest that hemopoietic stem cells with constitutional pericentric inversion of chromosome 9 [inv(9)] may be related to delayed engraftment or hemopoietic defect after stem cell transplantation (SCT). We conducted a retrospective study on five allogeneic SCT in which constitutional inv(9) was detected either in the donor or the recipient. The results showed that hematologic recovery was within the expected time range for all our patients. However, one patient exhibited decreasing blood counts between day +45 and +272 after transplantation, possibly due to protracted cytomegalovirus (CMV) infection and gansiclovir and imatinib treatment. Our findings suggest that constitutional inv(9) may not be associated with delayed hemopoietic recovery after SCT.

Bisphosphonate-induced avascular osteonecrosis of the jaws: a clinical report of 11 cases.

Bisphosphonates are compounds used in the treatment of various metabolic and malignant bone diseases. In the last 2 years there has been a significant increase in referrals to the Department of Oral and Maxillofacial Surgery of patients with exposed necrotic jaw bone, diagnosed elsewhere as chronic refractory osteomyelitis of jaws, mostly after several teeth extractions. The only clinical feature in common for all the patients was the use of bisphosphonates in the treatment of bone diseases. A retrospective study was performed of 11 patients with necrotic bone lesions of the jaws of various extents referred to this Department from July 2003 to November 2004. The management of the patients included cessation of bisphosphonate therapy for 2-8 months and various surgical restorative procedures thereafter. Four patients (36%) presented with maxillary bone involvement, 6 (55%) had mandibular bone necrosis and 1 (9%) presented with necrosis at 3 quadrants. All patients had received bisphosphonate therapy for 6 months to 5 years. Biopsies from the necrotic lesions revealed no metastatic disease. One patient who was removed from bisphosphonate therapy for 8 months recovered completely, one other who was not removed from bisphosphonate therapy relapsed and for all the others, with cessation of bisphosphonate therapy for 2-6 months, the results were inconsistent. A new complication of bisphosphonate therapy administration, i.e. osteonecrosis of jaws, seems to be developing. The improved results after cessation of the medication should make clinicians reconsider the merits of the rampant use of bisphosphonates, while further investigation is needed to completely elucidate this complication.

Treatment of early clinically staged Hodgkin's disease with a combination of ABVD chemotherapy plus limited field radiotherapy.

The current management of early stage Hodgkin's disease (HD) is usually based on clinical staging, combined modality therapy and the use of less toxic chemotherapy regimens. This approach entails high cure rates, while ensures less long term toxicity with avoidance of laparotomy. The aim of this study was to assess the efficacy of a brief course of Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by limited field radiotherapy (RT) in favorable clinical stage (CS) I and IIA HD. Forty patients, aged 17-68 (median 34) years, with favorable CS I and IIA HD, without bulky mediastinal disease, have been treated with 4-6 (median 4) cycles of ABVD plus limited field RT. Twenty seven (67%) patients received 4 cycles of chemotherapy, while 13 received 5-6 cycles. Thirty five (87%) patients received limited field RT with dose 24-36 Gy and five (13%) received extended field with 36-46 Gy. All patients responded completely to chemotherapy. One patient experienced a relapse two months after the end of therapy. All patients are alive; 39 in continuous complete remission. With a median follow-up period of 44 months (range 18-101) the actuarial overall and progress free survival was 100 and 97% at 5 years. We did not observe any case of secondary leukemia or solid tumor. Pulmonary toxicity was mild in cases of mediastinal irradiation. Considering the short follow-up time and the small number of patients, the combination of a brief course of ABVD plus regional RT is a very efficacious treatment of favorable CS I and IIA HD with mild toxicity. However, long term survival data are needed, which could give confident answers regarding the risk of late therapy related complications, particularly second malignancies.

Treatment of squamous cell carcinoma of the anterior faucial pillar-retromolar trigone.

Cancer of the anterior faucial pillar-retromolar trigone is an uncommon head and neck tumor, which has historically been shown to be associated with poor prognosis. In this retrospective study, we reviewed our experience with primary surgery followed by postoperative radiation therapy in order to determine the impact of our treatment protocols on patients' outcome. Between January 1994 and December 1998, 31 patients with histologically proven squamous cell carcinoma (SCC) of the anterior faucial pillar-retromolar trigone were treated in our department. Surgical excision of the primary lesion and ipsilateral neck dissection were performed in all patients. Reconstruction was accomplished using masseter muscle flap or tongue flap. Postoperatively, most patients (90%) received radiation therapy (51-58 Gy) to the primary side and neck. Adjuvant chemotherapy was offered if histologic signs of aggressive behavior were identified. Four out of 31 patients were initially seen at stage I or II and 27 patients at stage III or IV of the disease. Metastatic disease was demonstrated in 78% of ipsilateral neck nodes. Occult metastases were found in 64% of clinically N0 necks. The 3-year loco-regional recurrence rates were 44.8%. SCC of retromolar trigone is considered as an aggressive and insidious tumor. The reconstruction of the deficit of the anterior faucial pillar-retromolar area with masseter muscle flap is a reliable, safe and absolutely functional method.

The inferiorly and superiorly based nasolabial flap for the reconstruction of moderate-sized oronasal defects.

PURPOSE: The usefulness of the inferiorly or superiorly based nasolabial flap for the unilateral or bilateral reconstruction of local extraoral and intraoral defects was evaluated. PATIENTS AND METHODS: In a 10-year period, 22 flaps were used in 15 patients to cover defects of the floor of the mouth, nose, and chin. Fourteen bilateral and two unilateral flaps were inferiorly based, and six unilateral flaps were superiorly based. RESULTS: Dehiscence, which occurred in one case, and obstructive sialadenitis which occurred in another, were the main complications. CONCLUSION: The nasolabial flap is a useful procedure for the reconstruction of moderate-sized oronasal defects because of its simple elevation, proximity to the defect, and versatility.

Correction of the protruding ear with a modified anterior scoring technique.

PURPOSE: This article describes a modified anterior scoring technique to provide natural-looking results after correction of the protruding ear. The modified technique is described, and its advantages are compared with the conventional anterior scoring technique and with the other two basic techniques (Converse and Mustardé). PATIENTS AND METHODS: The modified technique was used to treat eight patients. In these cases, the use of transfixion mattress sutures placed through the perichondrium was very helpful in achieving a smooth curvature. RESULTS: Results up to 1 year showed no alteration in form when compared with the short-time results. CONCLUSION: The conventional anterior scoring technique for otoplasty is one of the most useful and reliable techniques, applicable in all cases of prominent ears. However, in some cases, it is difficult to control the cartilage bending completely. By using three adjusting mattress sutures (4-0 vicryl) through the perichondrium on the posterior side, combined with shallower scoring incisions, it is possible to create symmetry with the opposite ear and prevent "telephone ear" complication.

Incidence of human papillomavirus 6, 11, 16, 18 and 33 in normal oral mucosa of a Greek population.

The polymerase chain reaction (PCR) was applied for the detection of human papillomavirus (HPV) infection in samples obtained from the clinically normal mucosa of the oral cavity of 169 asymptomatic subjects in northern Greece. Of the subjects, 9.5% were found to be infected with HPV. Typing of HPV by Southern blot hybridization revealed that 2.4%, 0%, 0%, 4.1%, 0.6% of the subjects were infected with HPV 16, 18, 33, 6 and 11, respectively.

Tympanic plate fracture following mandibular trauma.

Bleeding from the external auditory canal following head trauma is not unusual. It can be caused by a posterior dislocation of the mandibular condyle associated with a fracture of the tympanic bone. Although posterior dislocation is uncommon, it is the second most frequent complication after antero-medial displacement of the condyle. We report four cases of tympanic plate fracture and present CT images demonstrating the range of injuries seen.

Agenesis of sphenoid sinus. Case report.

Although the sphenoid sinuses can be identified in sections of the fetus at 4 months, at birth the sinus remains small and is little more than an evagination of the sphenoethmoid recess. After the 3rd year, invasion of the sphenoid bone is more rapid, and by the age of 7, the sinus has extended posteriorly to the level of the sella turcica. By the age of 12, the sphenoid pneumatization reaches its final form and a size equivalent to the adult, although further enlargement into the basisphenoid may occur in the adult. Agenesis of paranasal sinuses is an uncommon clinical sign and refers mainly to the frontal and secondarily to the maxillary sinuses. Agenesis of sphenoid sinuses is a very rare phenomenon in the literature. We present a 32-year-old male patient with agenesis of sphenoid sinuses that was studied by CT.