Summary:We enrolled 25 patients with extensive, steroid-refractory chronic graft-versus-host disease (cGVHD) in a prospective trial evaluating the efficacy of extracorporeal photophoresis (ECP) in both skin and visceral cGVHD. The median time from transplant to initiation of ECP was 790 days. ECP was administered for 2 consecutive days every 2 weeks in 17 patients and once a week in eight patients until best response or stable disease. The median duration of therapy was 9 months (range 3-24 months). In all, 20 patients had improvement in cutaneous GVHD and six had healing of oral ulcerations. Steroid sparing or discontinuation of immunosuppressive medications was possible in 80% of patients. Response rates were similar between patients receiving treatment weekly vs every 2 weeks and in patients commencing ECP less than vs greater than 18 months from transplant (70 vs 66%). When patients were stratified based on the Akpek prognostic score, there was no difference in overall response between the favorable (Akpek scoreo2.5) and unfavorable risk groups, but patients with progressive onset cGVHD tended to have a higher response than those with de novo onset. In summary, we report improvement in skin and/or visceral cGVHD in 71% overall and 61% of high-risk patients.

This strategy of brief intensive chemotherapy for young children with non-metastatic medulloblastoma eliminated the need for craniospinal irradiation 52% of the patients, and may preserve QoL and intellectual functioning. The excellent survival rates are somewhat dampened by high toxic mortality.

Renal medullary carcinoma (RMC) is one of the most aggressive renal cell carcinomas. It predominantly afflicts young adults and adolescents with sickle cell trait and other sickle hemoglobinopathies, and is refractory to targeted and anti-angiogenic therapies used in patients with clear-cell renal cell carcinoma. Platinum-based cytotoxic chemotherapy is the mainstay for RMC treatment. Based on recent advances in the diagnosis, management, and clinical trial development for RMC, a panel of experts met in October 2017 and developed updated consensus recommendations to inform clinicians, researchers, and patients. Because RMC often aggressively recurs while patients are still recovering from nephrectomy, upfront chemotherapy should be considered for the majority of patients, including those with localized disease. After safety and dosing information have been established in adults, phase II and III trials enrolling patients with RMC should allow patients aged 12 years and older to be accrued. Patients with the very rare unclassified renal cell carcinoma with medullary phenotype variant should be included in RMC trials. Medical providers should be aware that RMC can afflict subjects of all races, and not only those of the African descent, and that the presence of sickle cell trait, or of other sickle hemoglobinopathies, can impact drug responses and toxicity.

Summary:In all, 55 patients at high risk or ineligible for a conventional allogeneic hematopoietic stem cell transplant (HSCT) received a regimen consisting of extracorporeal photopheresis, pentostatin, and reduced dose total body irradiation. The median age was 49 years (18-70 years); 44 received a sibling and 11 an unrelated HSCT; 44% were over the age of 50 years and 31% had undergone a prior HSCT. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. Full donor chimerism was documented in 98% by day þ 100. The 1000-day nonrelapse mortality was 11%. The median follow-up is 502 days (154-1104 days). The 1-and 2-year overall survival (OS) and event-free survival (EFS) are 67, 58 and 55%, and 47%, respectively. Patients who had not received a prior HSCT or had less than three prior chemotherapy regimens had a 71% OS and 67% EFS at 1 year. Greater than grade II aGVHD developed in 9% and chronic GVHD (cGVHD) in 43%, and extensive in 12% and limited in 31%. Of the patients, 86% who engrafted had a disease response, 72% had complete and 14% partial responses. This novel reduced intensity preparative regimen was well tolerated and associated with a low incidence of transplant-related mortality and serious acute and cGVHD. pentostatin Current allogeneic hematopoietic stem cell transplant (HSCT) preparative regimens are designed to administer the maximally tolerated doses of chemotherapy and/or radiation therapy in an attempt to eradicate residual disease, ablate host hematopoiesis, and immune suppress the recipient to ensure engraftment of donor hematopoietic stem cells (HSC). While this approach is curative for many patients, it is also associated with 30-50% transplantrelated mortality (TRM) in patients over the age of 50 years. 1 While advances in supportive care and the management of acute graft-versus-host disease (aGVHD) have decreased the TRM and morbidity associated with an allogeneic HSCT, its application remains limited to patients who are able to tolerate the side effects of high-dose chemotherapy administered as part of a conventional preparative regimen. 2 Recent studies suggest that disease control and engraftment of allogeneic HSCT can be achieved following nonablative doses of chemoradiotherapy. [3][4][5] Moreover, in various diseases, the beneficial effects of the allogeneic HSCT result from an immune-mediated graft-versus-malignancy (GVM) effect and not from the high doses of chemotherapy administered in the preparative regimen. [5][6][7][8] Stable full or partial donor stem cell engraftment following the administration of a nonablative, reduced intensity preparative (RIT) regimen may also provide a platform for subsequent immune modulation to augment the GVM effect. [7][8][9] Compared to conventional, ablative preparative regimens, RIT regimens are generally associated with a decrease in TRM and other transplant-related complications. 3,7,10,11 However, despite a decrease in regimen-related toxicities, serious aGVHD and cGVHD remain a major cause of TRM and morbidi...

The strategy of low dose chronic exposure to a topoisomerase inhibitor along with ablative carboplatin and thiotepa with stem cell rescue showed promising survival outcomes in these relapsed patients. This treatment strategy deserves further evaluation in a larger group of high-risk or relapsed primary CNS tumors.

9507 Background: The use of dose-intensive chemotherapy with autologous hematopoietic cell rescue (AuHCR) is a potentially curative approach to the management of infants and young children with non-metastatic (M-0) medulloblastoma, with the additional benefit of avoiding the late effects of irradiation. We report the results of the “Head Start” I (1991 to 1997) and “Head Start” II (1997 to 2002) clinical trials, using this approach, to treat children with M-0 medulloblastoma, who were less than three years of age at diagnosis. Methods: Twenty one children were enrolled on these two serial studies. After surgery, patients received a uniform induction chemotherapy regimen consisting of five cycles of vincristine, cisplatin, cyclophosphamide and etoposide. Following completion of induction, all patients underwent myeloablative consolidation chemotherapy using carboplatin, thiotepa and etoposide followed by AuHCR, and did not receive irradiation. Irradiation was used only at relapse. Quality of life (QoL) and social and emotional behavior were evaluated on “Head Start” I, and cognitive functioning was evaluated on “Head Start” II survivors. Results: The five-year event-free (EFS) and overall survival (OS) rates (±SE) for all patients, patients with gross total resection, and patients with residual tumor were 52 ± 11% and 70 ± 10%, 64 ± 13% and 79 ± 17%, and 29 ± 17% and 57 ± 19%, respectively. The five-year EFS and OS (±SE) for patients with desmoplastic and classical medulloblastoma were 67 ± 16% and 78 ± 14%, and 42 ± 14 and 67 ± 14%, respectively. Young age (<2 years versus 2 to 3 years) at diagnosis did not appear to impact adversely upon outcome. There were four treatment related deaths. A majority of survivors (71%) avoided irradiation altogether. Neuropsychological functioning in children surviving without irradiation was well within the normal range for most patients. Conclusions: The strategy of brief intensive chemotherapy without irradiation for young children with M-0 medulloblastoma has eliminated the need for craniospinal irradiation in over half (52%) of the patients, with preservation of QoL and cognitive functioning in the majority. No significant financial relationships to disclose.

Background: Despite universal newborn screening available in the United States, babies with sickle cell disease (SCD) are often born to parents who did not know they had sickle cell trait (SCT) before pregnancy. The objective of this study was to assess the knowledge of SCD and SCT among adolescents and their caregivers in our community.