e24127 Background: Supportive care is considered essential to standard care for patients with a history of cancer. The interdisciplinary team at Sidney Kimmel Cancer Center (SKCC) of Thomas Jefferson University, an NCI-designated cancer center in Philadelphia, offers a robust variety of supportive care services including support groups, educational and wellness programs. SKCC includes four academic hubs across the Greater Philadelphia region. With the onset of the COVID-19 pandemic and the subsequent statewide shutdown of services, SKCC quickly pivoted to virtual offerings, to address patients’ supportive care needs. Recent research has shown patients self-reporting higher incidence of anxiety and loneliness due to the pandemic. Direct patient feedback identified programs of greatest need, the preferred times and format. Methods: At the beginning of the pandemic SKCC offered a program “Coping with Cancer and Covid-19: as You Navigate Cancer Treatment.” This program helped patients understand their risk of COVID-19 and provided emotional support as patients and caregivers began facing loneliness. Additional virtual offerings included Mindfulness Sessions, Yoga, Stretching for Stress Relief, Healing through Humor. SKCC began evaluating the impact of the programming beginning in June 2020. Attendees completed surveys evaluating the presentation, their level of psychological distress, perceived quality of life, and feelings of hope, loneliness, and connection. Participants were asked if they would attend another program and were asked to rate the program on a Likert scale. Results: In 2019 SKCC offered 273 programs and attracted 984 participants. Only 90 of the 984 participants attended virtually prior to the pandemic. Since the start of the pandemic, SKCC has hosted 334 programs, all virtually, with 3,346 participants. Surveys were sent electronically and completed immediately after the completion of all support programs offered at SKCC. 40% of program participants’ completed an evaluation form and 94% rated the program exceptional or very good. Overall, 88% of participants in virtual wellness, support groups and educational programs indicated they would attend another program offered by SKCC. Conclusions: Virtual supportive care offerings have engaged more patients and caregivers than ever across SKCC hubs and have proven an effective means to continue to support patients during the pandemic. It is important to continue to evaluate and create meaningful programs to match the ongoing needs of patients and caregivers.[Table: see text]
BackgroundGI symptoms are common after CBT & GI aGVHD is frequent. The correlation between symptoms, macroscopic appearance (macro), histology, aGVHD severity & therapy response, however, is not established.MethodsWe analyzed 1st endoscopies done days +21-180 in engrafted adult double unit CBT recipients transplanted 10/2009-12/2017 with Cy 50/ Flu 150/ Thio 5-10/ TBI 400 & CSA/ MMF. All patients (pts) received fungal prophylaxis, early CMV pre-emptive therapy & C. difficile/ viral PCR stool assays (& blood for adenovirus) were routinely performed. Abnormal histology was defined as mild (grade 1-2) vs severe (grade 3-4).ResultsOf 156 pts, 88 pts (56%) [median 49 years (range 22-66), 65 leukemia, 5 MDS/ MPD, 18 NHL/ HL] were scoped. Their median donor-recipient HLA-allele match was 5/8 (range 3-7) & 36 (38%) pts also received haplo-CD34+ cells. Pts had 44 upper, 2 lower & 42 combined upper/ lower scopes at a median of 52 days (range 22-176) post-CBT.Of 86 pts who had upper scopes (Table 1), 67/86 (78%) were treated for upper GI aGVHD & only 3 had infection (Figure). The majority (51/67,76%) of aGVHD treated pts had normal macro appearance & the majority (49/67, 73%) had aGVHD compatible histology (typically apoptotic epithelial cells, mild in all but 2). Overall, the majority of treated pts (48/67, 72%) had a day 28 CR (37 budesonide, 11 high dose corticosteroids). Of 18 treated pts with normal macro & histology, 11 had CR & 7 PR. Nearly all (40/44, 91%) pts who had lower GI scopes (Table 2) were treated for aGVHD & none had infection (Figure). Most (33/40, 83%) were stage I-II (< 1000 mls stool/ day). Notably,17/33, (51%) stage I-II pts had normal macro, but most of these (14/17, 82%) had aGVHD compatible histology (typically apoptotic epithelial cells, crypt loss & mucosal denudation). Most stage I-II pts (25/33, 76%) had day 28 CR (17 budesonide, 8 high dose corticosteroids). Six of 7 stage 3-4 pts had abnormal macro, all had aGVHD histology, & only 3/7 had day 28 CR to high dose corticosteroids. Moreover, only 2/6 pts with severe histology had day 28 CR.ConclusionsWith pre-emptive CMV therapy, yeast prophylaxis, & stool PCR studies, the majority of CBT pts who required endoscopies had aGVHD & infection was very rare. This was especially true in pts with diarrhea. Normal mucosal appearance was frequent in aGVHD treated pts & nearly all pts with diarrhea & abnormal macro had aGVHD. Most had aGVHD compatible histology (usually mild). Notably, 9/23 treated pts with normal histology only had a PR supporting aGVHD is a clinical diagnosis. Moreover, pts with severe histologic abnormality were at high risk for PR/ refractory disease. This data supports early corticosteroid therapy if aGVHD compatible symptoms & not waiting for biopsy results. This is critical in pts with diarrhea. Correlation of this data with serum biomarkers & microbiota to improve the efficiency of diagnosis & risk stratification are needed. GI symptoms are common after CBT & GI aGVHD is frequent. The correlation between symptoms, macroscopic appearance (macro), histology, aGVHD severity & therapy response, however, is not established. We analyzed 1st endoscopies done days +21-180 in engrafted adult double unit CBT recipients transplanted 10/2009-12/2017 with Cy 50/ Flu 150/ Thio 5-10/ TBI 400 & CSA/ MMF. All patients (pts) received fungal prophylaxis, early CMV pre-emptive therapy & C. difficile/ viral PCR stool assays (& blood for adenovirus) were routinely performed. Abnormal histology was defined as mild (grade 1-2) vs severe (grade 3-4). Of 156 pts, 88 pts (56%) [median 49 years (range 22-66), 65 leukemia, 5 MDS/ MPD, 18 NHL/ HL] were scoped. Their median donor-recipient HLA-allele match was 5/8 (range 3-7) & 36 (38%) pts also received haplo-CD34+ cells. Pts had 44 upper, 2 lower & 42 combined upper/ lower scopes at a median of 52 days (range 22-176) post-CBT. Of 86 pts who had upper scopes (Table 1), 67/86 (78%) were treated for upper GI aGVHD & only 3 had infection (Figure). The majority (51/67,76%) of aGVHD treated pts had normal macro appearance & the majority (49/67, 73%) had aGVHD compatible histology (typically apoptotic epithelial cells, mild in all but 2). Overall, the majority of treated pts (48/67, 72%) had a day 28 CR (37 budesonide, 11 high dose corticosteroids). Of 18 treated pts with normal macro & histology, 11 had CR & 7 PR. Nearly all (40/44, 91%) pts who had lower GI scopes (Table 2) were treated for aGVHD & none had infection (Figure). Most (33/40, 83%) were stage I-II (< 1000 mls stool/ day). Notably,17/33, (51%) stage I-II pts had normal macro, but most of these (14/17, 82%) had aGVHD compatible histology (typically apoptotic epithelial cells, crypt loss & mucosal denudation). Most stage I-II pts (25/33, 76%) had day 28 CR (17 budesonide, 8 high dose corticosteroids). Six of 7 stage 3-4 pts had abnormal macro, all had aGVHD histology, & only 3/7 had day 28 CR to high dose corticosteroids. Moreover, only 2/6 pts with severe histology had day 28 CR. With pre-emptive CMV therapy, yeast prophylaxis, & stool PCR studies, the majority of CBT pts who required endoscopies had aGVHD & infection was very rare. This was especially true in pts with diarrhea. Normal mucosal appearance was frequent in aGVHD treated pts & nearly all pts with diarrhea & abnormal macro had aGVHD. Most had aGVHD compatible histology (usually mild). Notably, 9/23 treated pts with normal histology only had a PR supporting aGVHD is a clinical diagnosis. Moreover, pts with severe histologic abnormality were at high risk for PR/ refractory disease. This data supports early corticosteroid therapy if aGVHD compatible symptoms & not waiting for biopsy results. This is critical in pts with diarrhea. Correlation of this data with serum biomarkers & microbiota to improve the efficiency of diagnosis & risk stratification are needed.
Highlights•In patients without matched unrelated donors, neither cord blood nor haploidentical donor availability is guaranteed•Heavier African patients are at most risk for lack of suitable cord blood grafts•Medical and/or psychosocial problems can be barriers to haploidentical donor access in adult patients•African ancestry patients are at greatest risk for lack of suitable haploidentical donorsAbstractThe availability of cord blood (CB) and haploidentical (haplo) donors in all patient populations is not established. We have investigated the addition of haplo-CD34+ cells to CB grafts (haplo-CBT) to speed myeloid engraftment. Thus, we have prospectively assessed CB and haplo donor availability in adult patients without 8/8 HLA-allele matched unrelated donors (URDs). Analysis of 89 patients eligible for haplo-CBT revealed 4 distinct patient groups. First, 6 patients (7% of total, 33% non-European) underwent CBT only as they had no suitable family members to type. In group 2, 49 patients (45% non-European) received haplo-CBT using the first haplo donor chosen. Group 3 (n = 21, 76% non-European) underwent CBT with/without haplo. In this group, the first haplo donor chosen failed clearance in 20 patients and transplantation was too urgent to permit donor evaluation in 1. Fifty-three haplo donors were evaluated (2 to 6 per patient) for 21 group 3 patients, and 43 of 53 (81%) haplos failed clearance for predominantly medical and/or psychosocial reasons. Group 4, (n = 13, 85% non-European with a high median weight of 96 kilograms) had no CB grafts with/without no haplo donors. Overall, African patients had the worst donor availability with only 65% having a suitable CB graft and only 44% having a suitable haplo donor. Additionally, in non-European patients, a greater number of haplos required evaluation/patient to secure a suitable haplo graft. Although these data should be confirmed in a larger study, it suggests that there are barriers to the availability of both CB and haplo grafts in adult patients without 8/8 URDs, especially in those with African ancestry, and has multiple practical implications for patient management.
IntroductionOptimal CB unit selection incorporates TNC & CD34+ cell dose & 8-allele donor-recipient HLA-match. How graft characteristics for these parameters vary by patient (pt) race/ ethnicity, however, is unknown.MethodsWe analyzed cryopreserved TNC & CD34+ cell content, the cell dose incorporating pt weight, & HLA-match of infused & backup (reserved but not shipped) units by pt ancestry in CB transplant (CBT) recipients transplanted 7/2013-6/2018. Units were chosen based on banking practices, TNC & CD34+ dose & 4-6/6 & 8-allele HLA-match. Patient (pt) racial/ ethnic origins were prospectively obtained & grouped per Barker J. et al, BBMT 2010.ResultsThe characteristics of 544 units chosen for 144 diverse CBT recipients by pt ancestry are shown (Table 1). 286 units were infused (142 doubles, 2 singles) & pts had a total of 258 backup units (0-2/pt). The median TNC content of units for Europeans was higher than for Non-Europeans (216 vs 197, p = 0.002). Units for NW Europeans had the highest median TNC content with lowest in units for Africans & White Hispanics. Units chosen for Europeans also had a higher median CD34+ cell content than Non-Europeans (160 vs 132, p = 0.007). Units for NW Europeans had the highest & units for Africans the lowest median CD34+ content. Median TNC/kg was similar in units for European & Non-European pts (2.7 vs 2.5, p = 0.11) & differences between groups were not marked. However, there was a trend for units for Europeans having a higher median CD34+ dose than units for Non-Europeans (1.9 vs 1.7, p = 0.057) with disparity between groups. Although the median 8 allele HLA-match was 5/8 for units chosen for both European & Non-European pts, units identified for non-Europeans were more mismatched (p = 0.017).When the 286 transplanted units (considered the best) were analyzed, the median TNC & CD34+ contents of units were higher for Europeans than non-Europeans (232 vs 216, p = 0.022, & 181 vs 152, p = 0.009). As shown in Table 2, while there were no overall differences in the median TNC & CD34+ doses of units for Europeans & non-Europeans, differences in cell content combined with differences in weights resulted in TNC & CD34+ dose disparities within ancestry groups. For example, NW Europeans (high weight, high CD34+ content) had the highest CD34+ doses; lower content in Asian pts was partially compensated for by low weight; African pts (high weight, low content) had the lowest doses. Finally, there was marked differences in HLA-match distribution by ancestry group: eg only 23% of units for NW Europeans were 3-4/8 vs 40% for S. Europeans, 46% for white Hispanics & 51% for Africans.ConclusionsCB extends transplant access to minorities but differences in cellular content translates to many ancestry groups pts having access to only lower dosed units. There are also marked racial/ ethnic disparities in HLA-match. This data supports continued funding of banks to further increase the CB inventory.
BackgroundAdult dCBT recipients are at significant risk for aGVHD especially involving the GI tract. Investigation of augmented prophylaxis is indicated.MethodsBased on adult donor allograft data (Kennedy et al, Lancet 2015; Drobyski et al Haematologica 2018), we are investigating the addition of a single dose of tocilizumab 8 mg/kg (cap 800mg) on day -1 to standard cyclosporine/ MMF starting day -3 in adult patients (pts) with hematologic malignancies undergoing intermediate intensity Cy 50/ Flu 150/ Thio 10/ TBI 400 dCBT. We report an interim analysis of the first 16 pts of a 27 pt phase II trial (NCT03434730). All pts received standard bacterial/ fungal prophylaxis & Letermovir if CMV seropositive.Results16 pts [median 50 years (range 27-59), median 85 kg (range 59-125), 6 AML, 5 ALL, 2 MPAL, 2 MDS, 1 CML, median aaHCT-CI of 3 (range 0-6)] received double-unit CB grafts with a median CD34+ cell dose of 1.33 × 105/kg/unit (range 0.24-3.83) & median unit-recipient 8-allele HLA-match of 5/8 (range 3-6). Pt outcomes are shown (Table). All (100%) pts engrafted with a median neutrophil recovery of 26 days (range 19-40). 94% of pts engrafted platelets (median 44 days, range 32-59). All pts had single unit dominance (median day 28 blood winning unit chimerism 100% (range 58-100). Prior to engraftment, 11/16 (69%) had no neutropenic fever, 3/16 (19%) pts had fever with bacteremia, 1 pt (6%) had febrile neutropenia (duration 2 days) responding to antibiotics, & 1 pt (6%) had initial fever due to bacteremia followed by fever/ rash attributed to pre-engraftment syndrome (PES). An additional 2 pts developed rash without fever prior to engraftment attributed to PES. Thus, a total of 3/16 (19%) pts had PES (onset ranging 12-14 days). Ten pts developed grade II aGVHD (median onset 45 days, range 26-81) for a cumulative incidence of 63% (95%CI: 33-82). This was limited primarily to skin &/or the upper gut with one pt having stage I lower GI. No pt has developed grade III-IV aGVHD & no pt has had stage II-IV lower GI aGVHD to date (Figure). With a median follow-up of 147 days (range 74-214), 15 pts are alive & disease-free (1 death due to HHV-6 pneumonitis).ConclusionsPreliminary data suggests tocilizumab is safe with no adverse effects upon engraftment or unit dominance. Tocilizumab mitigates PES (expected incidence 65% in dCBT controls, Bhatt et al, ASBMT 2019). Expected days of febrile neutropenia were also reduced especially given the prolonged neutrophil recovery. Notably, lower gut aGVHD appears markedly reduced with no cases of grade III-IV aGVHD or aGVHD mortality to date. Our findings appear consistent with the published adult donor data. Overall, one tocilizumab dose has improved the early post-dCBT morbidity & investigation of this promising & potentially cost-effective approach is ongoing. Adult dCBT recipients are at significant risk for aGVHD especially involving the GI tract. Investigation of augmented prophylaxis is indicated. Based on adult donor allograft data (Kennedy et al, Lancet 2015; Drobyski et al Haematologica 2018), we are investigating the addition of a single dose of tocilizumab 8 mg/kg (cap 800mg) on day -1 to standard cyclosporine/ MMF starting day -3 in adult patients (pts) with hematologic malignancies undergoing intermediate intensity Cy 50/ Flu 150/ Thio 10/ TBI 400 dCBT. We report an interim analysis of the first 16 pts of a 27 pt phase II trial (NCT03434730). All pts received standard bacterial/ fungal prophylaxis & Letermovir if CMV seropositive. 16 pts [median 50 years (range 27-59), median 85 kg (range 59-125), 6 AML, 5 ALL, 2 MPAL, 2 MDS, 1 CML, median aaHCT-CI of 3 (range 0-6)] received double-unit CB grafts with a median CD34+ cell dose of 1.33 × 105/kg/unit (range 0.24-3.83) & median unit-recipient 8-allele HLA-match of 5/8 (range 3-6). Pt outcomes are shown (Table). All (100%) pts engrafted with a median neutrophil recovery of 26 days (range 19-40). 94% of pts engrafted platelets (median 44 days, range 32-59). All pts had single unit dominance (median day 28 blood winning unit chimerism 100% (range 58-100). Prior to engraftment, 11/16 (69%) had no neutropenic fever, 3/16 (19%) pts had fever with bacteremia, 1 pt (6%) had febrile neutropenia (duration 2 days) responding to antibiotics, & 1 pt (6%) had initial fever due to bacteremia followed by fever/ rash attributed to pre-engraftment syndrome (PES). An additional 2 pts developed rash without fever prior to engraftment attributed to PES. Thus, a total of 3/16 (19%) pts had PES (onset ranging 12-14 days). Ten pts developed grade II aGVHD (median onset 45 days, range 26-81) for a cumulative incidence of 63% (95%CI: 33-82). This was limited primarily to skin &/or the upper gut with one pt having stage I lower GI. No pt has developed grade III-IV aGVHD & no pt has had stage II-IV lower GI aGVHD to date (Figure). With a median follow-up of 147 days (range 74-214), 15 pts are alive & disease-free (1 death due to HHV-6 pneumonitis). Preliminary data suggests tocilizumab is safe with no adverse effects upon engraftment or unit dominance. Tocilizumab mitigates PES (expected incidence 65% in dCBT controls, Bhatt et al, ASBMT 2019). Expected days of febrile neutropenia were also reduced especially given the prolonged neutrophil recovery. Notably, lower gut aGVHD appears markedly reduced with no cases of grade III-IV aGVHD or aGVHD mortality to date. Our findings appear consistent with the published adult donor data. Overall, one tocilizumab dose has improved the early post-dCBT morbidity & investigation of this promising & potentially cost-effective approach is ongoing.
