Increasing access to transplantation through telemedicine and patient navigation.

BACKGROUND: Hematopoietic cell transplantation (HCT) is a promising treatment for hematological diseases, yet access barriers like cost and limited transplant centers persist. Telemedicine-based patient navigation (PN) has emerged as a solution. This study presents a cost-free PN telemedicine clinic (TC) in collaboration with the National Marrow Donor Program. AIM: to assess its feasibility and impac on HCT access determined by the cumulative incidence of transplantation. METHODS: In this single-center cohort study, patients of all ages and diagnoses referred for HCT participated. Two transplant physician-navigators established patient relationships via video calls, collecting medical history, offering HCT education and recommending pretransplant tests. The analysis involved descriptive statistics and intent-to-transplant survival assessment. RESULTS: One hundred and three patients were included of whom n = 78 were referred for allogeneic HCT (alloHCT), with a median age of 28 years. The median time from initial contact to the first consult was 5 days. The cumulative incidence of transplantation was 50% at 6 months and 61% at 12 months, with varying outcomes based on HCT type. Notably, 49 patients were not transplanted, primarily due to refractory disease, progression or relapse (57.1%). Autologous HCT candidates and physician referrals were correlated with higher transplant success compared to alloHCT candidates and patients who were not referred by a physician. CONCLUSION: Our pretransplant TC was feasible, facilitating access to HCT. Disease relapse posed a significant barrier. Enhancing timely physician referrals should be a focus for future efforts.

Rituximab desensitization in pediatric acute lymphoblastic leukemia with severe anaphylaxis.

INTRODUCTION: Hypersensitivity reactions (HSRs) to rituximab occur during the first infusion in 29% to 40% of patients. Commonly, these hypersensitivity reactions are the result of a release of cytokines, although IgE mediated reactions have also been reported. CASE REPORT: A 7-year-old female patient with diagnosis of CD-20 positive acute lymphoblastic B-cell leukemia was included in a pilot study that consisted of two doses of rituximab treatment in the induction to remission phase by the pediatric hematology service; 30 minutes after the first administration of 300 mg of rituximab the patient started with generalized rash, nausea, vomiting, tachycardia, dyspnea, foreign body sensation in throat, oxygen desaturation until 89% and hypotension; therefore, the infusion of rituximab was suspended, and intramuscular epinephrine was administered as well as intravenous hydrocortisone and chlorphenamine and supplemental oxygen supply with adequate resolution of symptoms. MANAGEMENT & OUTCOME: Intradermal skin testing with rituximab at the concentration 1 mg/ml (dilution 1:10), was positive. Desensitization to rituximab was indicated by our service with 4 bags - 16 steps protocol with an initial concentration dose of 1/1,000 of the total dose. The patient was premedicated 1 hour prior with intravenous chlorphenamine, methylprednisolone and ondansetron. Intravenous prophylactic fluids with normal saline solution were administered during the infusion. The procedure was carried out with close monitoring of vital signs in a course of 6.67 hours, without presenting hypersensitivity reactions. DISCUSSION: HSR to rituximab may be induced by the activation of mast cells and basophils. Desensitization protocols are developed when there is no alternative drug for the underlying condition.

Outpatient low toxic regimen with bortezomib in relapsed/refractory acute lymphoblastic leukemia in pediatrics and AYA patients: Single-center Mexican experience.

Relapsed or refractory acute lymphoblastic leukemia represents a major challenge in low- and middle-income countries where new therapies are not easily accessible. Combinations of cost-effective drugs should be considered as a bridge for hematopoietic stem cell transplantation. We retrospectively analyzed pediatric and adolescent and young adult patients who received reinduction with a protocol based on l-asparaginase, doxorubicin, vincristine, dexamethasone, and bortezomib (BZ). Fifteen patients were included. Total complete response (CR) was achieved by nine of 15 patients (60%); five patients achieved CR with negative minimal residual disease, two achieved complete morphological response (CR), and two complete morphological response without platelet recovery. Eleven patients (73%) were not hospitalized and 10 (66%) did not require any blood component transfusions. There were no cases of serious toxicity or mortality. Nine patients (60%) underwent transplant. Five-year overall survival was 40%. This BZ-based protocol is effective and safe when administered as an outpatient regimen and feasible in a low resource setting.

Cyclosporine A for the Prevention of Ocular Graft versus Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients Is Safe and Feasible.

PURPOSE: To evaluate the safety and efficacy of ocular cyclosporine in the prevention of the development of ocular graft versus host disease (oGVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT) in comparison with historic data. DESIGN: We developed a longitudinal, observational, prospective nonrandomized study. We evaluated the feasibility of prophylactic use of topical cyclosporine A (CsA) to prevent or decrease the incidence of oGVHD and compared this with historic data. METHODS: Patients undergoing AHSCT were treated with prophylactic topical CsA for 12 months after engraftment, followed by serial ophthalmic evaluations, including the Schirmer test. RESULTS: Twenty patients were included. No serious adverse effects were reported. Poor adherence was documented in 15% of patients. In spite of observing extra-ocular GVHD (acute and chronic GVHD incidence of 50 and 45%, respectively), only 1 in 20 patients developed oGVHD over the 20-month follow-up for the entire cohort. No statistically significant difference was observed in the incidence of oGVHD when compared to a historical cohort. CONCLUSIONS: Topical CsA as a prophylactic measure for oGVHD, administered over a period of 1 year after grafting, is safe and feasible and may decrease the incidence of ophthalmic manifestations of GVHD. These findings must be confirmed in a randomized trial.

Efficacy of three filgrastim-intended copies for hematopoietic stem cell mobilization in healthy adult and pediatric donors in Mexico.

INTRODUCTION: The use of filgrastim biosimilars for healthy adult and pediatric donor mobilization in hematopoietic stem cell transplantation has been met with increased safety and efficacy concerns in contrast to generic small molecule drugs. In Mexico, several filgrastim-intended copies (FIC) have been available and marketed since 2001, while no clinical comparability studies to evaluate their use in this setting have been published and thus are not considered to be true biosimilars. In this study, we report our experience using three different FIC products currently available (Filatil, Dextrifyl, and Biofilgran). METHODS: We retrospectively evaluated 118 related donors of all ages who received any brand 5 µg/kg subcutaneously twice daily for 4 days and were harvested in a single apheresis system on day 5. RESULTS: Donors had a median age of 38 years (range, 1-69). A successful harvest defined as ≥2 × 106 CD34+ cells/kg of recipient weight was achieved in 95.8% of cases, with a median CD34+ cell dose of 9.4 × 106 /kg (range 1-42.8). A single apheresis session was performed in 89.8% of cases. No significant difference in cell yield between each brand was observed. All pediatric donors had a successful harvest with similar results to adult donors. No immediate severe adverse effects were documented in any case. CONCLUSIONS: In conclusion, three FICs available in Mexico were efficacious and without immediate severe adverse effects, resulting in significant cost savings. Evaluation of immunogenicity and establishment of a pharmacovigilance program with the use of FICs is warranted.

Haploidentical peripheral blood stem cell transplantation with posttransplant cyclophosphamide in children and adolescents with hematological malignancies.

BACKGROUND: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using posttransplant cyclophosphamide (Cy) for graft versus host disease (GVHD) prophylaxis has emerged as an alternative transplant strategy for patients without related donors, especially in the setting of limited resources in which T-cell ex vivo depletion is not affordable. Experience with this transplant modality in children and adolescents is limited. PROCEDURE: We report a retrospective analysis of 25 consecutive outpatients under 21 years of age with high-risk hematological malignancies, who received a haplo-HSCT using posttransplant Cy as GVHD prophylaxis. RESULTS: Twenty-three (92%) of the 25 patients engrafted, and 20 (95%) of 21 evaluable subjects achieved full donor chimerism by day +30. One-year estimated overall survival and event-free survival were 50% and 33%, respectively. The cumulative incidence rate of severe acute GVHD was 19%, and 15% of patients developed chronic GVHD. CONCLUSIONS: Haplo-HSCT with posttransplant Cy is a feasible therapeutic option for children and adolescents with high-risk hematological malignancies in a limited resource setting.

[Comparison of the effectiveness of hematopoietic cell mobilization with chemotherapy and filgrastim versus filgrastim alone for autologous transplant in patients with lymphoma.] / Comparación de la efectividad de la movilización de células hematopoyéticas con quimioterapia y filgrastim, o con filgrastim solo, para autotrasplante en pacientes con linfoma.

INTRODUCTION: Autologous hematopoietic stem cell transplantation is the treatment of choice for high-risk Hodgkin's lymphoma and non-Hodgkin's lymphoma. OBJECTIVE: Compare the capacity to mobilize CD34+ cells for autologous hematopoietic stem cell transplantation using schemes with chemotherapy and without chemotherapy plus filgrastim in patients diagnosed with Hodgkin's lymphoma or non-Hodgkin's lymphoma. MATERIAL AND METHODS: The clinical records of patients with Hodgkin's lymphoma or non-Hodgkin's lymphoma who received an autologous hematopoietic stem cell transplant were analyzed retrospectively. Filgrastim alone or in combination with chemotherapy was used as mobilization scheme. Cell harvesting was classified as adequate when > 2 × 106 cells/kg were collected. RESULTS: Forty-seven patients (Hodgkin's lymphoma, 24; non-Hodgkin's lymphoma, 23) were included. Comparing groups of Hodgkin's lymphoma mobilized with chemotherapy (15 patients) and without chemotherapy (nine patients), one apheresis procedure was sufficient in 73 and 44% of patients, respectively (p = 0.04), the average of CD34 + cells/kg collected was 11 x 106 and 3 x 106, respectively (p = 0.017), and the collection was adequate in 100 and 55.6% of cases, respectively (p = 0.014). Comparing the groups of non-Hodgkin's lymphoma mobilized with chemotherapy (six patients) and without chemotherapy (17 patients), one apheresis procedure was sufficient in 33 and 65% of patients, respectively (p = 0.26), the average of CD34+ cells/kg was 3.56 x 106 and 3.41 x 106, respectively (p = 0.47), and collection was adequate in 66.6 and 59% of cases, respectively (p = 0.37). CONCLUSION: In Hodgkin's lymphoma patients, mobilization schemes with chemotherapy were more effective considering the number of cells collected, the number of apheresis required, and the percentage of successful cell collections. In non-Hodgkin's lymphoma patients, there were no significant differences between the two groups.

Haploidentical Bone Marrow Transplantation in 2015 and Beyond.

On the face of the lack of HLA-identical sibling stem cell donors for all individuals needing an allograft, the use of alternative donors is gaining popularity. Matched unrelated donors and cord bloods have become very expensive and unaffordable for most people living in developing countries. Grafting allogeneic haploidentical stem cells has become an option with a great future, mainly if the procedure is conducted in a way to cut down expenses, such as the use of reduced-intensity conditioning regimens, outpatient conduction of the procedures, and use of post-transplant cyclophosphamide. The long-term results of allografting haploidentical stem cells seem to be similar to those of grafting cord blood stem cells. The improvement of the procedures to conduct haploidentical stem cell transplantation will most likely result in more individuals gaining access to this type of treatments, critical in the current practice of hematology.

Effective collection of peripheral blood stem cells in children weighing 20 kilogram or less in a single large-volume apheresis procedure.

INTRODUCTION: Peripheral blood stem cell (PBSC) transplantation has become a routine procedure in pediatric oncology. A special group of PBSC donors are children weighing 20 kg or less. Limited vascular access and low blood volume puts them at a higher risk. Central line placement and a priming apheresis machine are recommended to avoid these complications. PATIENTS AND METHODS: PBSC collections performed from July 2006 to May 2013 in children weighing less than 20 kg were included. All donors had a central venous catheter (CVC). An apheresis machine was primed with packet red blood cells. RESULTS: Twenty-seven PBSC collections were performed in 22 children weighing 20 kg or less, 14 for allogeneic and 8 for autologous transplantation, in order to collect at least 2 × 10(6) CD34+ cells/kg. In the allogeneic group, median age and weight were 3 years (0.8-7) and 15.5 kg (8-20). In the autologous group, median age and weight were 3 years (2-7) and 15.35 kg (12.5-19.5). A single large-volume apheresis was sufficient to obtain the CD34+ cells needed in 78.5% and 75% of the allogeneic and autologous groups, respectively, with a median 11.84 × 10(6) and 5.79 × 10(6) CD34+ cells collected per kilogram of weight of the recipient. No serious complications related to the apheresis procedure or CVC placement occurred. CONCLUSION: PBSC collection in a single large-volume apheresis for allogeneic and autologous transplants in children weighing 20 kg or less is a safe and effective procedure when based on standardized protocols.

Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: an open-label phase I trial.

BACKGROUND AIMS: Cerebral palsy (CP) is related to severe perinatal hypoxia with permanent brain damage in nearly 50% of surviving preterm infants. Cell therapy is a potential therapeutic option for CP by several mechanisms, including immunomodulation through cytokine and growth factor secretion. METHODS: In this phase I open-label clinical trial, 18 pediatric patients with CP were included to assess the safety of autologous bone marrow-derived total nucleated cell (TNC) intrathecal and intravenous injection after stimulation with granulocyte colony-stimulating factor. Motor, cognitive, communication, personal-social and adaptive areas were evaluated at baseline and 1 and 6 months after the procedure through the use of the Battelle Developmental Inventory. Magnetic resonance imaging was performed at baseline and 6 months after therapy. This study was registered in ClinicaTrials.gov (NCT01019733). RESULTS: A median of 13.12 × 10(8) TNCs (range, 4.83-53.87) including 10.02 × 10(6) CD34+ cells (range, 1.02-29.9) in a volume of 7 mL (range, 4-10.5) was infused intrathecally. The remaining cells from the bone marrow aspirate were administered intravenously; 6.01 × 10(8) TNCs (range, 1.36-17.85), with 3.39 × 10(6) cells being CD34+. Early adverse effects included headache, vomiting, fever and stiff neck occurred in three patients. No serious complications were documented. An overall 4.7-month increase in developmental age according to the Battelle Developmental Inventory, including all areas of evaluation, was observed (±SD 2.63). No MRI changes at 6 months of follow-up were found. CONCLUSIONS: Subarachnoid placement of autologous bone marrow-derived TNC in children with CP is a safe procedure. The results suggest a possible increase in neurological function.

Allogeneic peripheral blood stem cell transplantation using reduced-intensity conditioning in an outpatient setting in ABO-incompatible patients: are survival and graft-versus-host disease different?

BACKGROUND: Graft-versus-host disease (GVHD) is a major cause of morbimortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Minor ABO incompatibility has been associated with an increased risk of GVHD. We analyzed the impact of ABO matching on patient outcome after peripheral blood, reduced-intensity allo-HSCT in an outpatient setting, and its relationship with GVHD. STUDY DESIGN AND METHODS: Data of 121 patients were included. All patients received allo-HSCT from HLA-identical siblings as outpatients using a reduced-intensity conditioning regimen. Influence of ABO matching as a risk factor for the development of GVHD and survival was analyzed using logistic regression and Cox proportional hazards regression, respectively. RESULTS: Median age was 36 years (range, 1-71 years); 88 patients were ABO identical: 13 presented major mismatch and 20 minor mismatch, with an ABO incompatibility rate of 27.3%. The median follow-up period was 54 months (range, 0.3-120 months). Minor ABO incompatibility patients presented the highest rate of acute GVHD (aGVHD; 25%), in comparison with ABO-identical (20.5%) and major ABO incompatibility patients (15.4%; p = 0.79). The highest incidence of chronic GVHD (cGVHD) occurred in the context of minor ABO incompatibility (35%), in contrast to ABO-identical (30.8%) and major ABO incompatibility (15.4%). Survival was higher for patients in the minor ABO mismatch group; however, there was no significant correlation between ABO matching status and survival (p = 0.45). CONCLUSION: Using this type of peripheral blood stem cell transplantation, minor ABO-mismatched allo-HSCT was associated with a higher incidence of aGVHD and cGVHD and with increased survival, albeit with no significance.

Lesson learned in pediatric haploidentical transplantation in a low-resource environment: delivering melphalan IV and using low dose radiation reduce graft failure.

Objectives: Primary graft failure (pGF) after hematopoietic stem-cell transplant is associated with considerable morbidity and mortality. The incidence in haplo-HSCT has been reported to be between 0% and 30%. In 2018, we identified a pGF incidence of 35% in our pediatric haplo-HSCT recipients with hematologic malignancies, which motivated us to enact changes to the conditioning regimen.Methods: We performed a single-center prospective, pre-post study of consecutive patients under 16 years with hematologic malignancies, from January 2015 to December 2022 who received a haplo-HSCT. Twenty-six pediatric patients received a haplo-HSCT before September 2018 (G1) and 36 patients after (G2). The main conditioning regimen for G1 was myeloablative with Flu/Cy/Bu, and for G2 the main regimen was reduced intensity Flu/Cy/Mel/TBI2.Results: Nine patients (35%) in G1 had primary graft failure, while in G2 there were no patients with pGF. The median follow-up for G1 was 15.9 months, and for G2 was 24.8 months, with an estimated overall survival at 12 months of 63% (95% CI 47-76) versus 85% (95% CI 73-93), and at 24 months of 47% (95% CI 31-64) versus 70% (95% CI 54-82) respectively (p = .007).Conclusion: After September 2018 conditioning regimen modifications were implemented with the objective of reducing primary failure, consisting mainly of switching from busulfan to melphalan as the alkylating agent of choice, and adding, when clinically possible TBI. Primary failure has been significantly reduced in our institution since then.

Overcoming challenges to reduce time to antibiotic therapy in febrile neutropenic children: insights from a Mexican center.

BACKGROUND: Providing quality supportive therapy for children with cancer is essential to reduce the high mortality rates in low- and middle-income countries. Febrile neutropenia is the most common life-threatening complication of cancer in children. The objective of this study was to evaluate the long-term effectiveness of the 'Golden Hour' intervention in reducing the time to administer antibiotics and its impact on clinical outcomes in a Mexican hospital. METHODS: A comparative study of children with febrile neutropenia who attended the emergency department at the Hospital Universitario "Dr. José Eleuterio González" was performed between January 2017 and December 2022. In May 2019, this center joined the collaborative 'Mexico in Alliance with St. Jude' project. An adapted improvement program was developed based on the implementation of an algorithm comprising institutional guidance, supplies kit, standardization of sample processing, training of healthcare providers, and patient education. The time to antibiotic administration was compared with clinical outcomes between the historical control and post-intervention groups. RESULTS: A total of 291 patients were included, 122 in the pre-intervention period and 169 in the intervention period. Only 5.7 % of the pre-intervention group received the first dose of antibiotics within 60 min of presenting to the emergency department compared to 84.6 % in the intervention group (p-value <0.000). The median times to antibiotic administration in the pre-intervention and post-intervention periods were 269.4 and 50.54 min, respectively (p-value <0.000). Clinical deterioration and admission to the pediatric intensive care unit decreased significantly from 6.6 % to 2.3 % (p-value = 0.03). CONCLUSIONS: Sustainability of the quality improvement project 'Golden Hour' in low- to mid-income countries demonstrated high effectiveness in reducing time to antibiotic administration among children with febrile neutropenia and improved clinical outcomes over three years of implementation.

Lactate/Pyruvate Ratio as an Early Predictor of Mortality in Patients with Sepsis: A Cohort Study.

Background: The lactate/pyruvate (LP) ratio has been studied as an alternative to serum lactate to determine clinical prognosis. Despite its clinical utility, there is a paucity of evidence evaluating the role of the L/P ratio in patients with sepsis. Methods: We assessed the clinical utility of the L/P ratio in patients with sepsis. The L/P ratio was measured at baseline, 4 and 8 h after admission. Our primary outcome was to determine the prognostic utility of the L/P ratio on the 15-day mortality risk. Our secondary outcomes were to compare the L/P ratio across time and its prognostic utility against standard risk calculators such as APACHE-II and SOFA scores. Results: We had a total of 80 patients, with 18 (22.5%) survivors and 62 (77.5%) non-survivors. While we found that patients having higher L/P ratios at 8 h had an increased 30-mortality risk (OR 1.08, 95% CI 1.02-1.18), the model's performance showed no difference when compared to other measurements of the L/P ratio that showed no association with mortality (p-value: 0.45). For our secondary outcome, we found that the APACHE-II and SOFA scores have better performance and predictability than the L/P ratio (AUC 0.83 and AUC 0.80, respectively), but showed no association with mortality (OR 1.07, 95% CI 1.01-1.17 and OR 1.08, 95% CI 1.02-1.18). Conclusions: Based on our findings, the L/P ratio appears to function more effectively as an early predictor of mortality when used as an adjuvant biomarker with other clinical parameters.

Real-world practice of acute leukemia intrathecal chemotherapy administration: A Mexican nationwide survey.

INTRODUCTION: Intrathecal chemotherapy is a mainstay component of acute lymphoblastic leukemia treatment. In Mexico, there is a considerable practice variability in aspects, such as the manner of preparation and the administration technique. OBJECTIVE: Our objective was to describe the different techniques used for the application of ITC and review the existing recommendations in the literature. METHOD: A cross-sectional, nationwide survey study was conducted by an electronic questionnaire sent to hematologists and oncologists in Mexico. We collected demographic data, personal experience, intrathecal chemotherapy techniques, drug preparation and postprocedural conduct. RESULTS: We received 173 responses. Twenty percent had an anesthesiologist administering sedation and pain management. The platelet count considered safe was 50 × 109/L in 48% of the participants. In 77% (n = 133) of the cases, the conventional needle with stylet used was, 49% did not receive any added diluent in the intrathecal chemotherapy and only 42% were recommended to rest in a horizontal position for more than 30 min. CONCLUSION: We identified a considerable variation in the administration of intrathecal chemotherapy across the hematologists in Mexico. We discuss the implications and opportunities in reducing the variation in our setting, highlighting the unmet need to establish guidelines that should be evaluated by the Mexican professional society to produce a position paper regarding practice standardization.

Mucopolysaccharidosis Type I in Mexico: Case-Based Review.

INTRODUCTION: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease present in 1:100,000 newborns. Variants in the IDUA (alpha-L-iduronidase) gene decrease the enzyme activity for glycosaminoglycans metabolism. MPS I patients exhibit clinical manifestations that fall on the Hurler, Hurler-Scheie, and Scheie syndrome spectrum. CASE PRESENTATION: We present a male Mexican patient with respiratory exacerbations requiring recurrent hospitalizations. He showed macrocephaly, coarse facies, hepatomegaly, umbilical hernia, and dorsal kyphosis. The sequencing of the IDUA gene revealed the following genotype: c.46_57del12/c.1205G>A. He received combined therapy with hematopoietic stem cell transplantation and enzyme replacement. Mexican case reports were analyzed to estimate the prevalence of the associated genetic variants. CONCLUSION: Despite the challenges of managing this rare disease in Mexico, our patient benefited from the combined therapy. The discrete clinical manifestations and prompt evaluation by a geneticist were crucial in establishing a diagnosis, enabling an early intervention by a multidisciplinary team. The combination of ERT before and after HSCT provided health benefits to our patient.

Effectiveness of subcutaneous low-dose alemtuzumab and rituximab combination therapy for steroid-resistant chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease is a common late complication of allogeneic hematopoietic stem cell transplantation. Corticosteroids are the standard initial treatment. Second-line treatment has not been well defined. We evaluated the effectiveness and safety of low doses of alemtuzumab plus low doses of rituximab in the treatment of steroid-refractory chronic graft-versus-host disease. DESIGN AND METHODS: Ten men and 5 women were prospectively included in the study. All patients received one cycle of subcutaneous alemtuzumab 10 mg/day/3 days and intravenous rituximab 100 mg on Days +4, +11, +18 and +25. The therapeutic response was measured on Days +30, +90 and +365 of the protocol. RESULTS: Median age was 41 years. The main site involved was the oral mucosa (86.7%) followed by the eyes (66.7%), liver (60%), skin (53%), lungs (13.3%) and intestinal tract (6.7%). The overall response was 100% at Day +30 evaluation: 10 patients (67%) had partial remission, 5 (33%) had complete remission. At Day +90 evaluation, 7 (50%) patients had partial remission, 4 (28%) had complete remission; 3 (21%) had relapsed chronic graft-versus-host disease and one patient did not reach the evaluation time point. So far, 5 patients have reached the Day +365 follow-up evaluation; 2 (40%) had partial remission, 2 had complete remission and one experienced chronic graft-versus-host disease progression. Adverse effects were mainly infections in 67% of patients; these were all quickly solved, except for one patient who died from pneumonia. CONCLUSIONS: This combination therapy appears to be an efficacious and safe treatment for steroid-refractory chronic graft-versus-host disease. Longer follow up to determine the durability of response and survival is required (ClinicalTrials.gov: NCT01042509).