Noncongenital Vaginal Obliteration: Surgical Restoration of Vaginal Patency for GVHD.

STUDY OBJECTIVE: To provide a brief overview of noncongenital causes of vaginal obliteration and stenosis, discuss a unique case of vaginal agglutination in a patient who developed genital graft-versus-host disease (GVHD) after receiving a bone marrow transplant (BMT), and present the steps of a laparoscopic total hysterectomy and lysis of vaginal adhesions that successfully restored vaginal patency without the need for grafting. DESIGN: This video gives an overview of noncongenital causes of vaginal obliteration with a focus on genital GVHD. SETTING: GVHD is a known possible complication of BMT. This condition can lead to vaginal obliteration, affecting sexual performance and quality of life. INTERVENTIONS: We discuss the clinical course of a 54-year-old female with history of acute monocytic leukemia treated with chemotherapy and a BMT. She subsequently developed genital GVHD with complete vaginal obliteration, precluding penetrative intercourse and causing pain, discomfort, and decreased quality of life. We present a combined laparoscopic and vaginal surgical procedure that allowed for the creation of a neovagina with a normal length and caliber. While grafting is sometimes necessary due to inflammation and scarring, we were able to avoid a graft by using a combined laparoscopic and vaginal approach, followed by restoration of continuity between the unaffected upper and lower vaginal tissues. CONCLUSION: GVHD can be quite debilitating for patients. A combined surgical approach is a feasible option for patients with complex pathology not amenable to simple transvaginal adhesiolysis. Surgical restoration of the vagina does not necessarily require the use of a graft if the anatomy is reestablished successfully. VIDEO ABSTRACT.

Diverting Enterostomy Improves Overall Survival of Patients With Severe Steroid-refractory Gastrointestinal Acute Graft-Versus-Host Disease.

OBJECTIVE: The aim of this study was to evaluate the benefit of diverting enterostomy (DE) in patients with severe steroid-refractory (SR) gastrointestinal acute graft-versus-host-disease (GI-aGVHD) following allogeneic hematopoietic stem-cell transplantation (ASCT). SUMMARY AND BACKGROUND DATA: Severe GI-aGVHD refractory to the first-line steroid therapy is a rare but dramatic life-threatening complication. Second lines of immunosuppressors have limited effects and increase the risk of sepsis. Data suggest that limiting GI bacterial translocation by DE could restrain severe GI-aGVHD. METHODS: From 2004 to 2018, we retrospectively reviewed all consecutive patients undergoing ASCT for hematologic malignancies who developed severe SR GI-aGVHD. We compared patients in whom a proximal DE was performed (Enterostomy group) with those not subjected to DE (Medical group). The primary endpoint was the 1-year overall survival (OS) measured from the onset of GI-aGVHD. Secondary endpoints were the 2-year OS and causes of death. RESULTS: Of the 1295 patients who underwent ASCT, 51 patients with severe SR GI-aGVHD were analyzed (13 in Enterostomy group and 38 in Medical group). Characteristics of patients, transplantation modalities, and aGVHD severity were similar in both groups. The 1-year OS was better after DE (54% vs 5%, P = 0.0004). The 2-year OS was also better in "Enterostomy group" (31% vs 2.5%; P = 0.0015), with a trend to lower death by sepsis (30.8% vs 57.9%; P = 0.091). CONCLUSION: DE should be considered for severe GI-aGVHD as soon as resistance to the corticosteroid is identified.

Solid organ transplantation after hematopoietic stem cell transplantation in childhood: A multicentric retrospective survey.

We report data obtained from a retrospective multicenter pediatric survey on behalf of the European Society for Blood and Marrow Transplantation (EBMT). Information on solid organ transplantation (SOT) performed in pediatric recipients of either autologous or allogeneic hematopoietic stem cell transplantation (HSCT) between 1984 and 2016 was collected in 20 pediatric EBMT Centers (25.6%). Overall, we evaluated data on 44 SOTs following HSCT including 20 liver (LTx), 12 lung (LuTx), 6 heart (HTx), and 6 kidney (KTx) transplantations. The indication for SOT was organ failure related to intractable graft-vs-host disease in 16 children (36.3%), acute or chronic HSCT-related toxicity in 18 (40.9%), and organ dysfunction related to the underlying disease in 10 (22.8%). The median follow-up was 10.9 years (95% confidence interval: 1.7-29.5). The overall survival rate at 1 and 5 years after SOT was 85.7% and 80.4%, respectively: it was 74% and 63.2% after LTx, 83.2% after HTx, and 100% equally after LuTx and KTx. This multicenter survey confirms that SOT represents a promising option in children with severe organ failure occurring after HSCT. Additional studies are needed to further establish the effectiveness of SOT after HSCT and to better understand the mechanism underlying this encouraging success.

Ileostomy for steroid-resistant acute graft-versus-host disease of the gastrointestinal tract.

Steroid-resistant acute graft-versus-host disease (GVHD) of the gastrointestinal tract associates with important morbidity and mortality. While high-dose steroids are the established first-line therapy in GVHD, no second-line therapy is generally accepted. In this analysis of 65 consecutive patients with severe, steroid-resistant, intestinal GVHD (92% stage 4), additional ileostomy surgery significantly reduced overall mortality (hazard ratio 0.54; 95% confidence interval, 0.36-0.81; p = 0.003) compared to conventional GVHD therapy. Median overall survival was 16 months in the ileostomy cohort compared to 4 months in the conventional therapy cohort. In the ileostomy cohort, both infectious- and GVHD-associated mortality were reduced (40% versus 77%). Significantly declined fecal volumes (p = 0.001) after surgery provide evidence of intestinal adaptation following ileostomy. Correlative studies indicated ileostomy-induced immune-modulation with a > 50% decrease of activated T cells (p = 0.04) and an increase in regulatory T cells. The observed alterations of the patients' gut microbiota may also contribute to ileostomy's therapeutic effect. These data show that ileostomy induced significant clinical responses in patients with steroid-resistant GVHD along with a reduction of pro-inflammatory immune cells and changes of the intestinal microbiota. Ileostomy is a treatment option for steroid-resistant acute GVHD of the gastrointestinal tract that needs further validation in a prospective clinical trial.

Allogeneic donor split skin grafts for treatment of refractory ulcers in cutaneous chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation-a retrospective analysis on seven patients.

Refractory skin ulcers due to severe chronic graft-versus-host disease (cGVHD) remain to be associated with significant morbidity and mortality.We performed an allogeneic donor skin transplantation in seven adult patients after allogeneic hematopoietic stem cell transplantation for cGVHD-associated refractory skin ulcers. While four patients received a split skin graft (SSG), in one patient, a full thickness skin graft for two small refractory ulcers of the ankle was performed, and one patient received in vitro expanded donor keratinocyte grafts derived from hair roots of the original unrelated donor. In one additional patient, a large deep fascial defect of the lower leg was covered with an autologous greater omentum free graft before coverage with an allogeneic SSG. An additional patient was treated with an autologous scrotal skin graft for a refractory ulcer associated with deep sclerosis of cGVHD after unrelated donor transplantation.All skin grafts engrafted and resulted in permanent coverage of the grafted ulcers without any signs of immunological mediated damage. In the patient receiving in vitro expanded keratinocyte grafts, two localized ulcers were permanently covered by donor skin while this approach failed to cover extensive circular ulcers of the lower legs.Allogeneic donor skin grafts are a valuable treatment option in refractory ulcers due to cGVHD but are restricted mainly to related donors while keratinocyte grafts from unrelated donors remain experimental. In male patients lacking a related donor, autologous scrotal skin graft may be an alternative option.

Long-Term Follow-Up of Sexual Dysfunction in Women Following Allogeneic Hematopoietic Stem Cell Transplantation.

Chronic graft-versus-host disease is the most common late complication following allogeneic hematopoietic stem cell transplantation. The aim of this study was to present the outcomes of two successful vaginal reconstructions. Patient 1 received chemotherapy for leukemia and underwent bone marrow transplantation (BMT). The patient was sexually inactive for 9 years. In 2012, she was diagnosed with complete vaginal obliteration and underwent vaginal reconstruction. Patient 2 underwent chemotherapy (myeloablative therapy), was sexually inactive for 3 years and was then diagnosed with complete vaginal obliteration. In January 2013, she had vaginal reconstruction with cervical dilatation. Hormonal replacement therapy was administered to both patients. The results of dedicated questionnaires revealed decent quality-of-life and normal sexual functioning and continence status after surgery. Obliteration of the vagina after BMT can be prevented, but if it occurs, vaginal reconstruction surgery should be offered to any patients suffering from obliteration. Our results show that this therapy enables patients to have normal sexual lives without compromising their continence status.

Clinical and Dermoscopic Evaluation of Melanocytic Lesions in Patients with Chronic Graft Versus Host Disease.

Patients treated with haematopoietic stem cell transplantation are at increased risk of cutaneous malignant neoplasms. There are no reports on the characteristics of melanocytic lesions in patients with chronic graft versus host disease and the value of recognizing these difficult lesions in high-risk patients. The objective of this study is to describe the clinical and dermoscopic characteristics of melanocytic lesions in patients with chronic graft versus host disease in order to understand their morphology. A prospective cross-sectional study was performed; 10 melanocytic lesions on the trunk and extremities were selected from each patient. A statistically significant association was found between regression and high total dermoscopic score and 7-point checklist score. Lesions were excised or included in short-term digital follow-up. Melanocytic lesions in patients with chronic graft versus host disease developing after allogeneic-haematopoietic stem cell transplantation exhibit marked structural and colour changes similar to melanoma. This is believed to result from the inflammatory process associated with graft versus host disease.

Translation of Clinical Research into Practice: An Impact Assessment of the Results from the Blood and Marrow Transplant Clinical Trials Network Protocol 0201 on Unrelated Graft Source Utilization.

Barriers and facilitators to adoption of results of clinical trials are substantial and poorly understood. We sought to examine whether the results of the randomized, multicenter Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 study comparing peripheral blood (PB) with bone marrow (BM) stem cells for unrelated donor (URD) hematopoietic cell transplantation (HCT) changed practice from PB to BM graft utilization and explored factors that impact graft selection and translation of research results into practice. The difference between use of URD BM and PB in the 2 years before and after publication of results in 2012 was examined using observational data collected by the Center for Blood and Marrow Transplant Research. A web-based survey of transplant physicians was conducted to understand the change in physician-reported personal and center preferred URD graft. No significant change in use of BM versus PB grafts occurred after 2012. Both BMT CTN participating and nonparticipating centers continued to use PB. Ninety-two percent of respondents were aware of the study results; 18% reported a change in personal and 16% reported a change in their center's practice of requesting BM instead of PB for URD HCT. Patient characteristics and the perception that engaging local champions to increase the evidence uptake were factors associated with personal or center change in practice. Despite awareness of the trial results, fewer than one-fifth of HCT physicians reported practice change in response to the BMT CTN 0201 results. Observational data confirmed no discernible change in practice.

Treatment of graft-versus-host disease with mesenchymal cells as a complication of a liver transplantation.

We present the case of a liver transplant (LT) recipient donor who developed graft versus host disease (GVHD). The main features were cutaneous rash, diarrhea and pancytopenia. Mesenchymal cells were administered as part of the treatment. This is the first case of a patient with GVHD after LT reported to date. Despite the treatment, there was no improvement in aplasia or gastrointestinal symptoms and the patient died due to a disseminated infection.

Graft versus host disease: what should the oculoplastic surgeon know?

PURPOSE OF REVIEW: To provide a concise review of the oculoplastic manifestations of ocular graft versus host disease (GVHD), and to discuss their management. RECENT FINDINGS: Ocular GVHD occurs as a common immune-mediated complication of hematopoietic stem cell transplantation that presents as a Stevens-Johnson-like syndrome in the acute phase or a Sjögren-like syndrome in the chronic phase. Cicatricial conjunctivitis may be underreported in ocular GVHD. The spectrum of oculoplastic manifestations includes GVHD of the skin, cicatricial entropion, nasolacrimal duct obstruction, and lacrimal gland dysfunction. Surgical treatment is indicated for patients with significant corneal complications from entropion. Surgical approach to repair of nasolacrimal duct obstruction is presented in this review, including modified approaches for treating patients at risk for keratitis sicca. Management of the ocular graft versus host patient may require a multidisciplinary approach involving collaboration from the oculoplastic surgeon, the corneal specialist, and the stem cell transplant physician. SUMMARY: Oculoplastic manifestations of ocular GVHD typically present as cicatricial changes in the eyelid and lacrimal system. Careful oculoplastic and corneal evaluation are necessary when considering surgical management for the ocular GVHD patient.

Umbilical Cord Blood Transplantation Is a Feasible Rescue Therapeutic Option for Patients Suffering from Graft Failure after Previous Hematopoietic Stem Cell Transplantation.

OBJECTIVE: Umbilical cord blood (UCB) is an important graft source for hematopoietic stem cell transplantation (SCT). Due to less stringent human leukocyte antigen (HLA) matching criteria compared to bone marrow or peripheral blood stem cells, UCB enables patients lacking an HLA-matched donor to receive potentially curative SCT. METHODS: We retrospectively analyzed the efficacy and safety of UCB transplantation (UCBT) at our center. RESULTS: Between June 2009 and June 2015, 27 UCBT were performed in 25 patients. Reasons for the use of UCB were lack of adequate related or unrelated stem cell donor (n = 20) and graft failure after previous SCT (n = 7). Median time to neutrophil engraftment was 22 days. Four patients experienced primary graft failure. Thirteen patients developed acute graft-versus-host disease (GVHD), whereupon 6 subsequently also developed chronic GVHD. After a median follow-up time of 19 months, 9 patients relapsed and 12 patients died. Cause of death was relapse in 8 and transplant-related events in 4 patients. Median overall survival and progression-free survival have not been reached yet. CONCLUSION: In our experience, UCBT is an alternative graft source for patients lacking a suitable related or unrelated donor and a feasible treatment option for patients experiencing graft failure after previous SCT.

Transplantation from haploidentical donor is not inferior to that from identical sibling donor for patients with chronic myeloid leukemia in blast crisis or chronic phase from blast crisis.

OBJECTIVES: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for chronic myeloid leukemia (CML) patients in blast crisis (BC), and haploidentical donors (HID) are immediately available for most patients. We compared the outcomes of HID transplantation with those of matched related donor (MRD) transplantation in a cohort study. PATIENTS AND METHODS: A total of 90 consecutive patients who received allogeneic HSCT because of CML-BC were investigated retrospectively. A total of 67 patients underwent transplantation from HID and 23 from MRD. Survival outcomes were compared between the two cohorts. RESULTS: Of the 90 patients, 86 patients were engrafted. Three-year overall survival (OS) and relapse-free survival (RFS) were comparable between HID and MRD recipients (OS: 60.0% vs 55.3%, respectively, P=.580; RFS: 51.1% vs 47.8%, respectively, P=.512). Three-year incidences of transplant-related mortality (TRM) and relapse did not differ between HID and MRD recipients (relapse: 21.0% vs 26.1%, respectively, P=.626; TRM: 27.9% vs 26.1%, respectively, P=.937). In multivariate analyses, previous chemotherapy history and not achieving CHR before HSCT are independent adverse predictors of OS. CONCLUSIONS: For CML-blast crisis or chronic phase from blast crisis patients, HID transplantation achieves comparable survival to MRD transplantation. HID donors can be regarded as regular donors for these special patients at selected centers.

Long-term remission of HSCT-related NS after a second allogenic stem cell transplant.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT)-related nephrotic syndrome (NS) is a rare event and has been described as a clinical form of chronic graft-versus-host disease (GVHD). Although immunological mechanisms are thought to play important roles in NS after HSCT, the exact mechanisms have not been clarified. CASE-DIAGNOSIS/TREATMENT: We report a 4-year-old boy with acute lymphoblastic leukemia (ALL) who developed NS during the tapering of immunosuppressants 5 months after an allogeneic HSCT (allo-HSCT). A renal biopsy was performed, and light and electron microscopy revealed minimal change disease (MCD). Although the response to treatment with steroids and tacrolimus was favorable, the child experienced two relapses of NS within the first 9 months after the initial response. A second allo-HSCT was performed to treat the relapse of ALL. After the second allo-HSCT, the remission of NS was maintained without recurrence for 5 years, even after the cessation of immunosuppressants. CONCLUSIONS: Our patient who had ALL and developed NS after his first allo-HSCT, maintained remission from NS after a second allo-HSCT. This suggests that the immune cells from the first donor origin were associated with the pathogenesis of NS.

Diagnostic accuracy of endoscopic features of pediatric acute gastrointestinal graft-versus-host disease.

BACKGROUND AND AIM: Acute gastrointestinal graft-versus-host disease (GI-GVHD) is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). There are very few studies on specific endoscopic findings in pediatric acute GI-GVHD. The aim of this retrospective case-control study was to elucidate the characteristic endoscopic findings in pediatric acute GI-GVHD that improve the diagnostic accuracy of endoscopy. METHODS: All consecutive patients under 18 years of age who underwent allogeneic HSCT in Kyoto University Hospital from May 2003 to October 2014 were identified retrospectively. Patients who underwent GI endoscopy as a result of sustained GI symptoms were identified. Intestinal villous patterns were evaluated by magnification endoscopy with the water-immersion technique. The patients were diagnosed with acute GI-GVHD and non-GVHD on the basis of biopsy histology. Endoscopic findings of the two groups were compared. RESULTS: Of the 171 patients who underwent HSCT, 30 underwent GI endoscopy. Of these, 17 and nine were diagnosed with acute GI-GVHD and non-GVHD, respectively. Compared with non-GVHD, acute GI-GVHD was associated significantly more often with short blunt villi in the duodenum (P = 0.013), variable defect villi and short blunt villi in the ileum (P = 0.009 and 0.035, respectively), and edema, erosion, and tortoiseshell-like mucosae in the colon (P = 0.017, 0.023, and 0.017, respectively). CONCLUSION: Pediatric acute GI-GVHD was associated with several characteristic features on magnifying endoscopy with the water-immersion technique. These features will be useful for endoscopic diagnosis of pediatric acute GI-GVHD.

Use of Prosthetic Replacement of the Ocular Surface Ecosystem Scleral Lenses in Patients with Ocular Chronic Graft-versus-Host Disease.

The purpose of this study was to evaluate the impact of prosthetic replacement of the ocular surface ecosystem (BostonSight PROSE, Boston Foundation for Sight, Needham, MA) treatment, utilizing customized scleral devices, on visual acuity, visual function, and ocular surface changes in patients with ocular chronic graft-versus-host disease (cGVHD). A retrospective analysis was performed on 79 eyes of 40 patients with cGVHD referred to the University of Southern California department of ophthalmology between November 2009 and July 2013 for PROSE treatment. This analysis included an assessment of ocular symptoms and visual function before and after treatment using the Ocular Surface Disease Index (OSDI) survey. Pre- and post-treatment visual acuity and clinical data were also compared. Twenty-eight male patients and 12 female patients were included in this study. The average age was 56.1 years (range, 27 to 74). Of the 79 eyes treated, 71 (90%) showed improved visual acuity with PROSE treatment. Fifty-seven eyes (72%) experienced a 2- or greater line visual acuity improvement and 14 eyes (18%) experienced a 1-line improvement. Average logarithm of the minimal angle of resolution improved from .49 ± .52 to .16 ± .44 (P < .0001), which correlates to a Snellen score improvement of approximately 20/60 to 20/30. Sixty-six of 79 eyes (84%) showed decreased corneal staining after treatment. All 9 eyes presenting with filamentary keratitis and 3 eyes with epithelial defects demonstrated complete healing of the epithelial surface after PROSE fitting. At post-treatment follow-up, 8 patients had died and 3 stopped wearing their devices. Of the remaining 29 patients, average OSDI scores improved from 72.6 ± 20.1 to 21.1 ± 14.9 (P < .0001). PROSE therapy, utilizing customized scleral lenses, can reduce ocular symptoms, improve visual acuity, and improve ocular surface integrity or appearance in patients with ocular cGVHD.

Colonoscopy and Sigmoidoscopy are Equally Effective for the Diagnosis of Colonic Acute Graft-versus-Host Disease in Patients with Diarrhea after Allogeneic Stem Cell Transplantation: A Prospective Controlled Trial.

Colonic acute graft-versus-host disease (aGVHD) affects approximately 10% of patients who have undergone allogeneic stem cell transplantation (allo-SCT). Diarrhea is a major clinical sign but also a common post-transplantation symptom in these patients. Comprehensive histopathologic examination of the colon is therefore regarded as crucial to establish a diagnosis, but the colonic segment that should be targeted for a diagnostic biopsy remains a topic of debate. The primary objective of this study was to compare prospectively colonoscopy with sigmoidoscopy regarding their capabilities to provide a histopathologically proven diagnosis of colonic aGVHD. Thirty-seven allo-SCT patients with diarrhea all underwent a colonoscopy. All biopsies collected from the descending colon were regarded as also attainable by sigmoidoscopy, whereas biopsies collected in regions further up the colon (from the transverse and ascending colon) were regarded as acquirable exclusively by colonoscopy. Biopsies attainable by colonoscopy and sigmoidoscopy were positive for GVHD in 25 (68%) and 24 (65%) patients, respectively (95% confidence interval for difference of proportions, -.185 to .245; P = .978; z = .0271 by the z-test). Sigmoidoscopy is as effective as colonoscopy in establishing a diagnosis of colonic aGVHD in patients who have diarrhea after allo-SCT.

Predictive value of bronchiolitis obliterans syndrome stage 0p in chronic graft-versus-host disease of the lung.

Bronchiolitis obliterans syndrome (BOS) is a significant post-transplant complication with low survival. BOS stage 0p (BOS 0p) is a parameter detected on pulmonary function tests (PFTs) after lung transplantation to identify patients at risk to develop BOS. We performed a retrospective study on 442 patients who underwent allogeneic stem cell transplant from 2007 to 2011 to evaluate whether development of BOS 0p is a risk factor in this population for BOS. Patients who met criteria for BOS 0p were significantly more likely to develop BOS (hazard ratio [HR], 3.22; P < .001). BOS 0p was significantly associated with a history of lung disease pretransplant (HR, 2.48; P = .001) and chronic graft-versus-host disease (GVHD) outside the lung post-transplant (HR, 23; P < .001). Finally, BOS 0p criteria were adequately sensitive in predicting BOS (85%), with a high negative predictive value (98%). Our findings suggest a routine PFT screening strategy with the intent of detecting BOS 0p, especially among patients with prior lung disease and who developed chronic GVHD, could suitably identify an at-risk population for the development of BOS.

Fetal membrane cells for treatment of steroid-refractory acute graft-versus-host disease.

The placenta protects the fetus from the mother's immune system. We have previously found that fetal membrane cells (FMCs) isolated from term placenta prevent alloreactivity in vitro. FMCs share many features with bone marrow-derived mesenchymal stromal cells (MSCs), which we previously introduced to treat severe acute graft-versus-host disease (GVHD). Here, we tested FMCs for treatment of steroid-refractory acute GVHD. After two passages in culture, approximately 10(9) FMCs were obtained from one single placenta, although not all cells from passage 0 and passage 1 were used for expansion. The FMCs were positive for CD29, CD44, CD73, CD90, CD105, and CD49d but were negative for hematopoietic, endothelial, and epithelial markers. Microsatellite polymorphism analysis showed that FMCs were of maternal origin. All FMCs used showed normal karyotype. Nine patients who had undergone hematopoietic stem cell transplantation (HSCT) and who had developed steroid-refractory grade III-IV acute GVHD were given 0.9-2.8 × 10(6) FMCs per kg at 15 infusions. Median age was 57 years. There was no toxicity from infusion of FMCs in eight patients. One patient had seizures after infusion. Two of eight evaluable patients had a complete response and four had a partial response, giving an overall response rate of 75%. Two patients showed no response at all. Three patients are alive from 6 to 21 months after HSCT. One patient is well and two have chronic GVHD. Thus, FMCs may be successfully used for immune modulation and tissue repair.

Lung transplantation following hematopoietic stem cell transplantation: report of two cases and systematic review of literature.

BACKGROUND: Non-infectious pulmonary complications following hematopoietic stem cell transplantation (HSCT) are major cause of morbidity and mortality with limited treatment options. Lung transplantation (LT) has been rarely reported as a treatment option for selected HSCT recipients with these problems. OBJECTIVE: Describe the outcome of HSCT recipients who underwent LT. METHODS: Two cases of LT following HSCT from our institution are presented. Cases reported in literature were identified using English language PubMed/MEDLINE with keywords hematopoietic stem cell transplantation, bone marrow transplantation, or bronchiolitis obliterans cross-referenced with lung transplantation. We extracted data on baseline characteristics and survival data following LT. RESULTS: Total of 84 patients are analyzed. Age at time of LT was median of 22 yr (range 1-66). Seventy-nine patients were recipients of allogeneic HSCT. The indications for LT were bronchiolitis obliterans syndrome (BOS; 63 patients), pulmonary fibrosis (13 patients), BOS/pulmonary fibrosis (five patients), and graft-versus-host-disease (GVHD) of lung (three patients). The median time between HSCT and LT was 52.3 months (range 6-240). The median follow-up after LT was 36 months (range 0-168). During this time, BOS was documented in 25 patients. Relapse of hematological malignancy was reported in two patients, and new malignancy developed in four patients. At the end of follow-up, 60 patients were alive and 24 patients died. The probability of survival following LT at 24 and 36 months was 0.88 (95% CI 0.78-0.93) and 0.79 (95% CI 0.67-0.87), respectively. CONCLUSION: LT is a potential therapeutic option in selected patients with severe chronic pulmonary disease following HSCT. Further studies are needed to determine the appropriate timing and the outcome of this approach.

Multiple infusions of mesenchymal stromal cells induce sustained remission in children with steroid-refractory, grade III-IV acute graft-versus-host disease.

Mesenchymal stromal cell (MSC) infusions have been reported to be effective in patients with steroid-refractory, acute graft-versus-host disease (aGvHD) but comprehensive data on paediatric patients are limited. We retrospectively analysed a cohort of 37 children (aged 3 months-17 years) treated with MSCs for steroid-refractory grade III-IV aGvHD. All patients but three received multiple MSC infusions. Complete response (CR) was observed in 24 children (65%), while 13 children had either partial (n = 8) or no response (n = 5). Cumulative incidence of transplantation-related mortality (TRM) in patients who did or did not achieve CR was 17% and 69%, respectively (P = 0.001). After a median follow-up of 2.9 years, overall survival (OS) was 37%; it was 65% vs. 0% in patients who did or did not achieve CR, respectively (P = 0.001). The median time from starting steroids for GvHD treatment to first MSC infusion was 13 d (range 5-85). Children treated between 5 and 12 d after steroid initiation showed a trend for better OS (56%) and lower TRM (17%) as compared with patients receiving MSCs 13-85 d after steroids (25% and 53%, respectively; P = 0.22 and 0.06, respectively). Multiple MSC infusions are safe and effective for children with steroid-refractory aGvHD, especially when employed early in the disease course.