Introduction Acute promyelocytic leukemia (APL) is a potentially curable malignancy with 4-year overall survival rates >90%. Early complications from the disease or its treatment may result in a loss of oral access and require alternative administration of medications. Tretinoin has been the backbone of APL therapy since the late 1990s and is only available as a liquid filled capsule. Case report Two patients with high-risk APL were unable to safely swallow tretinoin capsules due to complications of their disease. Management & outcome We prepared a tretinoin slurry using tretinoin 10 mg capsules, sterile water, and mineral oil at a ratio of 1 capsule to 2.75 mL sterile water to 1.25 mL mineral oil. This was successfully administered to both patients and no doses of tretinoin slurry were missed by either patient. In the patient who has long-term follow up available, a complete remission was achieved. Discussion Due to tretinoin’s known teratogenicity, this capsule should not be crushed, cut, or open, which limits its use in patients without oral access. Alternative routes of administration, such as via a nasogastric tube or sublingually, have not been safe and effective. By preparing a tretinoin slurry in our hazardous extemporaneous compounding area, we were able to safely and effectively prepare a tretinoin slurry that was successfully administered to two patients. This alternative preparation did not alter long-term outcomes and represents a viable option for patients who do not have oral access.
Purpose To evaluate a single institution's experience with granulocyte colony-stimulating factor after autologous hematopoietic stem cell transplant in myeloma patients to identify populations that benefit most from granulocyte colony-stimulating factor administration. Methods Retrospective chart reviews were conducted on patients 18+ years with multiple myeloma that underwent autologous hematopoietic stem cell transplant at UW Health from January 2012 to May 2016. Data collection included demographics, length of stay, time to engraftment, Eastern Cooperative Oncology Group performance status score, and hematopoietic cell transplantation-comorbidity index. The primary outcome was days from transplant to engraftment, defined as absolute neutrophil count > 500/mm for two consecutive days or absolute neutrophil count > 1000/mm once. A subset analysis was performed on patients whose date of engraftment was known. Results In total, 216 individual patients were included in the full cohort and 122 patients included in the subset analysis. Median time to engraftment between patients administered granulocyte colony-stimulating factor and the nongranulocyte colony-stimulating factor group was 12 versus 19 days (P < 0.001) in the full cohort and 12 versus 14 days (P < 0.001) in the subset analysis. The average length of stay posthematopoietic stem cell transplant in the granulocyte colony-stimulating factor group was 15 days versus 17 days in the nongranulocyte colony-stimulating factor group (P = 0.026) in the subset analysis. Additionally, no difference in time to engraftment was seen when stratified by age, Eastern Cooperative Oncology Group performance status score, or hematopoietic cell transplantation-comorbidity index. Conclusion Our study supports use of granulocyte colony-stimulating factor posthematopoietic stem cell transplant in myeloma patients to decrease time to engraftment and length of stay. Consideration should be given to utilization in all patients in this population posthematopoietic stem cell transplant. Further research is needed to identify the populations that benefit most from granulocyte colony-stimulating factor administration.
Introduction The current recommended granulocyte-colony stimulating factor (G-CSF) dose after autologous hematopoietic stem cell transplant (autoHSCT) in multiple myeloma patients is 5 mcg/kg/day administered subcutaneously until engraftment. Recently, our institution changed practice from weight-based to flat-dose G-CSF. The purpose of this study was to assess the impact of flat-dose G-CSF on time to engraftment among multiple myeloma patients of different weight groups. Methods Retrospective chart review was completed for adult patients with multiple myeloma who underwent autoHSCT from March 2018 through August 2019. Data collected included time to neutrophil engraftment, total length of hospitalization, length of stay post-transplant, time to platelet engraftment, use of intravenous fluconazole or acyclovir, parenteral nutrition use, incidence of febrile neutropenia, antibiotic use, and death. Differences in outcomes were compared between patients ≤80 kg versus those >80 kg. A secondary analysis was completed for patients ≤100 kg versus those >100 kg. Results There was no difference in time to neutrophil engraftment between weight groups (≤80 kg versus >80 kg: median = 12 days, p = 0.22; ≤100 kg versus >100 kg: median = 12 days, p = 0.52). There was a significant difference in intravenous fluconazole and acyclovir use between groups, with more use in the lower weight groups (≤80 kg versus >80 kg: 12 patients versus 10 patients p = 0.02; ≤100 kg versus >100 kg: 19 patients versus 3 patients p = 0.04). No significant differences were found for any other outcomes. Conclusion Utilizing a flat-dose of G-CSF for patients after autoHSCT does not appear to negatively affect patient outcomes. Institutions may benefit from using the 300 mcg dose of G-CSF for multiple myeloma patients after autoHSCT.
The University of Wisconsin Chemotherapy Council (UWCC) monitors the uniformity and appropriateness of chemotherapy administration at the University of Wisconsin Hospital and Clinics through a peer-review process. One aspect involves approval of "patient specific requests" (PSRs) that involve treatments not included in the institution's core regimens. Providers are asked to submit published evidence, information regarding pt. comorbidities, and clinical justification to support the application. However there is no current stipulation regarding demonstration of value, although implicit in this review process is to avoid futile, expensive or potentially harmful treatments. Given the ever burgeoning chemotherapeutic choices available for patients with any stage of disease, and the complexity of selecting an optimal therapeutic regimen, we hypothesized that some approved PSRs might have provided limited benefit to the pts who received them. Therefore, we undertook an analysis of PSRs specifically submitted for patients with leukemia and multiple myeloma (MM) between 1/1/2011 and 7/31/2014 to exam reasons for the submission as well as outcomes after the new therapy was initiated. METHODS: A total of 307 PSRs were reviewed by the UWCCC during this time period. Forty-one were specifically submitted and approved for patients with leukemia or MM. Reason for PSR, status at initiation, previous transplant, and days of hospitalization after PSR and 1 year survival were calculated. Table 1.DiagnosisNumberStatus at time of PSRPrevious TransplantMedian No previous regimensReason for PSR submissionPSR RegimenMean Survival After PSR starts1 yr. survivalAML, relapsed 8Refractory relapse88%3No SOC1Various236d (range 88-575d)12%AML, other2Remission01Nonstandard Transplant regimenTransplant regimen533 d100%CML, relapsed2RefractoryNo3Failed all previous regimensTransplant regimen289d50%ALL, newly diagnosed5UntreatedNA0Adult treated on pediatric regimen (n=3); elderly (n=2)Various551d (range 365-981d)100%ALL, relapsed5Relapsed20%3 (range 1-8)No SOC1CVP2, TKI3 based;, BFM4408d (range 167-735d)40%MM15Relapsed, refractory (n=15) 100%73% (auto)7 (range 2-10)Not core regimen (n=13) Rare subtype(n=2)PCP5 (n=3); CRD6 (n-4) other272 d ( range 74-661)60%APL4untreatedN/AN/ANot Core RegimenATRA/Arsenic, other788d (range 692-910d)100% 1SOC; 2cyclophosphamide, vincristine prednisone; 3tyrosine kinase inhibitor; 4Berlin/Frankfurt/Munich; 5Pomalidomide, cyclophosphamide, prednisone; 6carfilzomib, lenalidomide dexamethasone RESULTS: A total of 41 PSRs were examined. The most common reasons for submission of the PSR was request for a non-core regimen including a recently FDA approved use of an agent (n= 11); no current SOC established (n=13); salvage therapy with older regimen ((n=2). Median 1 yr. survival varied from 12% to 100% depending on diagnosis. Not surprisingly, APL pts displayed the best overall survival, followed by AML, transplanted with a nonstandard conditioning regimen. AML patients relapsing after previous allogeneic transplant had the worst survival, regardless of salvage regimen; only 1 pt. survived longer than 6 months. The median length of hospital stay in these patients following start of PSR was 43 d (range 14-54). Relapsed ALL pts also fared poorly, with 1 year survival of 40% and median days of hospitalization after PSR of 48d (range 0-117). Relapsed refractory MM pts had a variable outcome, with some pts surviving more than 3 years and others for only several months. CONCLUSION: Use of peer reviewed PSRs resulted in reasonable outcomes in most patients with leukemia and myeloma. However, pts with AML relapsing after allogeneic transplant and those with relapsed ALL fared particularly poorly despite treatment with a peer reviewed treatment plan, presumably chosen for best outcome. Furthermore, these salvage treatments were associated with lengthy hospital stays. Such patients are unlikely to benefit from any currently available regimens and may be more appropriately considered for clinical trials or supportive/ palliative care at time of relapse. Disclosures No relevant conflicts of interest to declare.
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