G-CSF Starting Day +1 after Autologous Transplant Is Safer Than Day +5 or Day +7 in Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5790-5790 ◽  
Author(s):  
Francesca Cottini ◽  
Douglas Sborov ◽  
Yu Kyoung Cho ◽  
Misty Lamprecht ◽  
Karen Tackett ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Standard Of Care ◽  
The Other ◽  
Severe Neutropenia ◽  
P Value ◽  
Post Transplant ◽  
Autologous Transplant ◽  
Significant Difference ◽  
Biochemical Progression

Abstract Introduction: For fit multiple myeloma (MM) patients, autologous hematopoietic stem cell transplant (HSCT) is standard of care as part of first line therapy, demonstrating longer progression-free survival when compared to upfront bortezomib, lenalidomide, and dexamethasone (IFM/DFCI 2009, ASH 2015). The use of granulocyte colony stimulating factor (G-CSF) after HSCT accelerates time to neutrophil recovery by 1 - 6 days when compared with control (Klumpp TR et al, JCO, 1995 & Schmitz N et al, BMT 2004). The American Society of Clinical Oncology guidelines recommend that G-CSF should be initiated 1-5 days after administration of high-dose chemotherapy and should be continued until the absolute neutrophil count (ANC) is 2000-3000/mm3 (Smith TJ, JCO, 2015). We have evaluated the role of G-CSF starting day +1, day +5, and day +7 post-transplant in three sequential cohorts of MM patients focusing on the duration of severe neutropenia (rather than the time to neutrophil engraftment), infections, and mucositis. Methods: As part of changes in the standard of care institutional protocols for autologous HSCT of myeloma patients at Ohio State University, three sequential cohorts of myeloma patients were identified that received G-CSF daily post-transplant until ANC>1500/mm3 or WBC>5/mm3. Two hundred twenty-six (226) patients received G-CSF on day +1 (n=43), day +5 (n=78), and day +7 (n=105) from May 2012 to August 2015. The majority of the patients received levofloxacin, acyclovir and fluconazole as prophylaxis. We evaluated the duration of severe neutropenia (ANC<500), the onset of bacteremia, WHO grade 2-4 mucositis, and the time to biochemical progression as part of an IRB approved protocol (NCT01653106). Results:The cohort of patients receiving G-CSF on day +5 had a shorter median follow up (455 days versus 979 days in the day +1 and 1355 days in the day +7 cohorts), since the patients were enrolled at a later timepoint. No statistically significant difference was noted in terms of age, gender, cytogenetic or ISS stage distribution, number of infused cells per kg, and melphalan dose among the three cohorts of patients. The duration of severe neutropenia was significantly increased for patients receiving G-CSF on day +7 (mean 153.4 hrs, SD 36.9) compared to those receiving G-CSF on day +1 (mean: 104.8 hrs, SD 19.4; p-value <0.0001) or day +5 (mean: 120.5 hrs, SD 27.4; p-value <0.0001). There was also a statistically significant difference between the duration of severe neutropenia for G-CSF day +1 or day +5 (p-value 0.013). The duration of neutropenia was not influenced by gender, International Staging System or R-ISS at diagnosis. Moreover, no statistically significant difference was noted in terms of duration of severe neutropenia when patients were subdivided based on the number of stem cell infused (< or > of 5 x 106 cells). Patients who received G-CSF on day +1 or day +5 had a significantly decreased incidence of grade 2 or higher mucositis (4.65% vs 10.3%) for day +1 and day +5 versus 21.9% for day +7 (fisher-test, p = 0.014 and 0.0255). Similarly, the incidence of bacteremia was decreased in those patients treated with G-CSF on days +1 and +5 versus day +7 (21.8%, 23.2%, and 33.3% for those treated on days +1, +5, and +7, respectively; p = 0.09). The group of patients who received G-CSF on day +5 had a longer length of stay, with two patients with prolonged hospitalization (mean 17.7 days, SD 5.6 days, range 12-49) when compared to the other groups (day +1 group mean 13.88 days, SD 2.8 days, range 10-21 versus day +7 group mean 15.2 days, SD 2.7 days, range 11-21 days; Two-tailed t-test p = 0.012). Lastly, our data indicates a trend, though not statistically significant, toward a longer time to biochemical progression in patients who received G-CSF on day +1 when compared to the other two groups. Conclusion: We conclude that starting G-CSF injections the day after stem cell infusion (day +1) decreases the duration of severe neutropenia, infections, and mucositis in comparison to day +5 and day +7 in patients receiving autologous transplant for MM. A prospective trial would definitively test this, but a multi-institution meta-analysis via CIBMTR would be more cost-effective, acknowledging that differing anti-infective prophylaxis regimens would prevent effective between institution comparisons of infection. Disclosures No relevant conflicts of interest to declare.

Phase I/II Trial of Bortezomib Maintenance in Order To Prolong Remission-Duration Following Autologous Peripheral Blood Progenitor Cell Transplantation as Treatment for Intermediate- and Advanced-Stage Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3617-3617 ◽  
Author(s):  
Gary J. Schiller ◽  
M. Liao ◽  
J.P. Sohn ◽  
R. Malone ◽  
K. Bartone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Treatment Cycle ◽  
The Other ◽  
Disease Assessment ◽  
High Dose ◽  
Advanced Stage ◽  
Post Transplant ◽  
Autologous Transplant

Abstract Pts (median age 60 yrs, range 37 – 73 yrs) with intermediate- and advanced-stage multiple myeloma were assigned to maintenance therapy with bortezomib beginning a minimum of three and a maximum of four mos after the day of autologous PBPC transplantation following a standard preparative regimen of high-dose melphalan (200 mg/m2). Eligibility for the initiation of maintenance required nl organ function, post-transplant neutrophil and plt recovery (defined as ANC ≥ 1000 mm−3 and untransfused plt ≥30,000 mm−3). Cohorts of 3 pts each were entered at 1 of 3 dose levels of bortezomib (1.0, 1.3, and 1.6 mg/m2) given IV q wk for 3 wks followed by a 1-wk rest period constituting 1 treatment cycle for a total of 8 cycles. To-date, 29 pts were eligible for study treatment and 23 pts received at least 1 dose of maintenance. Reasons for not proceeding to maintenance included 1 pt with an ANC &lt; 1000 mm−3, 1 pt with a serum creatinine &gt; 2 mg/dl, and 4 additional pts unable to travel to the center. The median t from diagnosis to transplant was 11.4 mos (range, 4.9 to 59.7 mos), and the median t from autologous transplant to the initiation of bortezomib maintenance was 3.7 mos. Protocol adherence was excellent with one pt missing the final dose of treatment and one other pt discontinuing therapy due to personal reasons. After completion of the Phase I portion of the study, the DLT was determined to be 1.6 mg/m2 based on grade 3 diarrhea in 2 pts after 2 and 3 cycles of treatment, respectively. All subsequent pts entered were treated at the MTD of 1.3 mg/m2. Other, non-dose-limiting toxicities included thrombocytopenia (14 pts), neuropathy (12 pts), anemia (12 pts), fatigue (11 pts), neutropenia (8 pts), musculoskeletal pain (7pts), nausea (5 pts), Herpes zoster reactivation (4 pts), diarrhea (3 pts), edema (3 pts), cough (2 pts), as well as upper respiratory infection, chills, fever, dyspepsia, and anorexia (1 pt each). Disease assessment consisted of serum and urine PEP monthly for all pts, and bone marrow aspiration quarterly for those pts with nonsecretory myeloma. Repeat bone surveys were required for pts 3, 9, 15, and 21 mos post-transplant. 2 pts required termination of the study drug, 1 at the end of treatment cycle 8 and the other during cycle 3, due to unacceptable side effects. 2 separate pts terminated the study due to disease progression, 1 during cycle 5 and the other during cycle 6, respectively. One additional pt discontinued further study treatments due to personal reasons during cycle 2. All 23 pts are eligible for response assessment. 13 pts continue to be followed every 3 mos for evidence of disease recurrence in the post-treatment period while 4 others continue on treatment. After a median follow-up from transplantation of 17.1 mos (range 4.1 to 30.3 mo), 6 pts have relapsed while none have died of recurrent myeloma. The current median relapse-free survival is 15.8 mos. This phase I/II trial demonstrates that bortezomib can be safely administered as a maintenance after conventional autologous PBPCl transplantation with an MTD of 1.3mg/m2 given 3 times per month for 8 mos; treatment consolidated remission achieved by autologous transplant as will be presented. These preliminary results, when compared to published results of autologous transplantation for myeloma, suggest that with further follow-up, bortezomib maintenance may favorably impact t- to-recurrence.

Bortezomib Does Not Impair Cytokine Induced Mobilization of Stem Cells Prior to Autologous Transplantation in Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2926-2926 ◽  
Author(s):  
Geoffrey L. Uy ◽  
Nicholas M. Fisher ◽  
Steven M. Devine ◽  
Michael H. Tomasson ◽  
John F. DiPersio ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Induction Therapy ◽  
High Dose ◽  
Front Line ◽  
Post Transplant ◽  
Autologous Transplant ◽  
Cd34 Cells ◽  
Stem Cell Collection

Abstract Bortezomib (VELCADE®) is a selective inhibitor of the proteasome approved for the treatment of relapsed or refractory multiple myeloma (MM). Emerging evidence indicates that bortezomib is also effective alone or in combination with cytotoxic agents in the front-line treatment of myeloma. Given the superiority of high dose therapy with autologous transplant compared to conventional therapy in myeloma, the application of bortezomib to novel front-line therapies depends in part on its effects on subsequent stem cell mobilization and engraftment. Previous reports have demonstrated successful chemotherapy induced mobilization of stem cells following bortezomib. To determine the effects of bortezomib on cytokine mobilization and engraftment of stem cells, we conducted a study of bortezomib administered prior to high-dose melphalan with autologous stem cell transplant. Following induction therapy, two cycles of bortezomib 1.3 mg/m2 were administered on days 1, 4, 8, and 11 of a 21-day treatment cycle. One week after the last dose of bortezomib, stem cells were mobilized with G-CSF 10 mcg/kg/day for 5 days and harvested by large volume apheresis (20 L/day) until a minimum of 2.5 x 106 CD34+ cells/kg were collected. Melphalan 100 mg/m2/day x 2 days was administered followed by reinfusion of peripheral blood stem cells 48 hours later. GM-CSF 250 mcg/m2/day was given post-transplant until the ANC ≥ 1,500/mm3 for 2 consecutive days. Forty patients were enrolled in this study with 37 continuing on to autologous transplant. Study population consists of 24 male and 16 female patients with the median age at enrollment of 56 years (range 38–69). Myeloma characteristics at diagnosis were as follows (number of patients): IgG (29), IgA (10), light chain only (1), with stage I (1), II (12), or stage III (27) disease. Prior to receiving bortezomib, 20 patients had been previously treated with an anthracycline containing regimen and 22 with thalidomide for induction therapy. Two patients did not receive any prior chemotherapy. Two patients did not proceed to stem cell harvest, one secondary to disease progression on bortezomib and the other because of a stroke suffered during G-CSF mobilization. Stem cell collection was successful in 37 of 38 patients with the first collection containing a median of 4.24 x 106 CD34+ cells/kg. The majority of patients (29) required a single pheresis session, 7 required two sessions, and 1 patient required 5 sessions. The only patient failing stem cell collection had received extensive radiation to the pelvis in addition to a prior history of breast cancer for which she received adjuvant chemotherapy. All transplanted patients successfully engrafted with a median time to neutrophil engraftment (ANC ≥ 500/mm3) of 11 days (range 9–14 days). Platelet engraftment (platelet count ≥ 20,000/mm3 sustained for 7 days without transfusion) occurred at a median of 11 days (range 9–31 days). In an intention-to-treat analysis at 100 days post-transplant, we observed a compete response (CR) in 6 patients (15%), a near CR in 10 patients (25%) with an additional 19 partial responses (48%) for an overall response rate of 88%. We conclude that pre-transplant treatment with 2 cycles of bortezomib following anthracycline or thalidomide containing chemotherapy does not adversely affect stem cell yield or time to engraftment and results in high CR / near CR rates.

Updated Results of a Phase I/II Trial of Autologous Peripheral Blood Progenitor Cell Transplantation with Velcade™ Maintenance as Treatment for Intermediate- and Advanced-Stage Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3710-3710 ◽  
Author(s):  
Mickey Liao ◽  
R Malone ◽  
K Bartoni ◽  
B Habtemariam ◽  
Ronald Paquette ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Treatment Cycle ◽  
The Other ◽  
Disease Assessment ◽  
High Dose ◽  
Advanced Stage ◽  
Free Survival ◽  
Post Transplant ◽  
Autologous Transplant

Abstract Pts (median age 59 yrs, range 38–73 yrs) with intermediate- and advanced-stage multiple myeloma were assigned to maintenance therapy with bortezomib beginning a minimum of three and a maximum of four mos after the day of autologous PBPC transplantation following a standard preparative regimen of high-dose melphalan (200 mg/m2). Eligibility for the initiation of maintenance required nl organ function, post-transplant neutrophil and plt recovery (defined as ANC ≥1000 mm−3 and untransfused plt ≥30,000 mm−3). Cohorts of 3 pts each were entered at 1 of 3 dose levels of bortezomib (1.0, 1.3, and 1.6 mg/m2) given IV q wk for 3 wks followed by a 1-wk rest period constituting 1 treatment cycle for a total of 8 cycles. To-date, 30 pts were eligible for study treatment and 24 pts received at least 1 dose of maintenance. Reasons for not proceeding to maintenance included 1 pt with an ANC < 1000 mm−3, 1 pt with a serum creatinine > 2 mg/dl, and 4 additional pts unable to travel to the center. The median t from diagnosis to transplant was 11.7 mos (range, 4.9 to 59.7 mos), and the median t from autologous transplant to the initiation of bortezomib maintenance was 3.1 mos. Protocol adherence was excellent with only 1 pt missing the final dose of treatment and 1 other pt discontinuing therapy due to personal reasons. After completion of the Phase I portion of the study, the DLT was determined to be 1.6 mg/m2 based on grade 3 diarrhea in 2 pts after 2 and 3 cycles of treatment, respectively. All subsequent pts entered were treated at the MTD of 1.3 mg/m2. Other, non-dose-limiting toxicities included fatigue (19 pts), musculoskeletal pain (17pts), neuropathy (10 pts), thrombocytopenia (9 pts), nausea (9 pts), diarrhea (7 pts), Herpes zoster reactivation (6 pts), neutropenia (6 pts), cough (3 pts), as well as upper respiratory infection, chills, fever, dyspepsia, rash and anorexia (1 pt each). Disease assessment consisted of serum and urine PEP monthly for all pts, and bone marrow aspiration quarterly for those pts with nonsecretory myeloma. Repeat bone surveys were required for pts 3, 9, 15, and 21 mos post-transplant. 2 pts required termination of the study drug, 1 at the end of treatment cycle 8 and the other during cycle 3, due to unacceptable side effects. 2 separate pts terminated the study due to disease progression, 1 during cycle 5 and the other during cycle 6, respectively. One additional pt discontinued further study treatments due to personal reasons during cycle 2. All 24 pts are eligible for response assessment. 11 pts continue to be followed every 3 mos for evidence of disease recurrence in the post-treatment period while 1 pt continues on active treatment. After a median follow-up from transplantation of 22.7 mos (range 8.7 to 39.5 mo), 10 pts have relapsed while 2 have died of recurrent myeloma. The current median relapse-free survival is 20.2 mos. This phase I/II trial demonstrates that bortezomib can be safely administered as a maintenance after conventional autologous PBPC transplantation with a MTD of 1.3mg/m2 given 3 times per month for 8 mos; treatment consolidated remission achieved by autologous transplant as will be presented. However, preliminary results with bortezomib maintenance suggest that progression free survival is not appreciably prolonged by this maintenance strategy.

scholarly journals Long-term outcome after allogeneic stem cell transplantation in multiple myeloma

2021 ◽  
Author(s):  
Sini Luoma ◽  
Raija Silvennoinen ◽  
Auvo Rauhala ◽  
Riitta Niittyvuopio ◽  
Eeva Martelin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Outcome ◽  
Significant Difference ◽  
Relapse Group

AbstractThe role of allogeneic hematopoietic stem cell transplantation (allo-SCT) in multiple myeloma is controversial. We analyzed the results of 205 patients transplanted in one center during 2000–2017. Transplantation was performed on 75 patients without a previous autologous SCT (upfront-allo), on 74 as tandem transplant (auto-allo), and on 56 patients after relapse. Median overall survival (OS) was 9.9 years for upfront-allo, 11.2 years for auto-allo, and 3.9 years for the relapse group (p = 0.015). Progression-free survival (PFS) was 2.4, 2.4, and 0.9 years, respectively (p < 0.001). Non-relapse mortality at 5 years was 8% overall, with no significant difference between the groups. Post-relapse survival was 4.1 years for upfront-allo and auto-allo, and 2.6 years for the relapse group (p = 0.066). Survival of high-risk patients was reduced. In multivariate analysis, the auto-allo group had improved OS and chronic graft-versus-host disease was advantageous in terms of PFS, OS, and relapse incidence. Late relapses occurred in all groups. Allo-SCT resulted in long-term survival in a small subgroup of patients. Our results indicate that auto-allo-SCT is feasible and could be considered for younger patients in the upfront setting.

Racial Disparity in Immediate Breast Reconstruction; a Gap That is not Closing

2021 ◽  
pp. 229255032110555
Author(s):  
Mahdi Malekpour ◽  
Sean Devitt ◽  
Joseph DeSantis ◽  
Christian Kauffman
Keyword(s):  
Propensity Score ◽  
Breast Reconstruction ◽  
Racial Disparity ◽  
Standard Of Care ◽  
Immediate Breast Reconstruction ◽  
P Value ◽  
National Cancer Database ◽  
Black Females ◽  
Black And White ◽  
Significant Difference

Background: Immediate breast reconstruction (IBR) is offered as part of the standard-of-care to females undergoing mastectomy. Racial disparity in IBR has been previously reported with a longstanding call for its elimination, though unknown if this goal is achieved. The aim of this study was to examine the current association between race and IBR and to investigate whether racial disparity is diminishing. Methods: Data was extracted from the National Cancer Database (NCDB) from 2004 to 2016. All variables in the database were controlled so that the comparison would be made solely between Black and White females. We also analyzed the trend in racial disparity to see if there has been a change from 2004 to 2016 after several calls for healthcare equality. Results: After propensity score matching, 69,084 White females were compared to 69,084 Black females. There was a statistically significant difference between the rate of IBR and race (23,386 [33.9%] in White females vs 20,850 [30.2%] in Black females, P-value  < .001). Despite a twofold increase in the rate of IBR in both White and Black females, a persistent gap of about 4% was observed over the study period, which translates to more than 2,500 Black females not receiving IBR. Conclusions: Using the NCDB database, a racial disparity was identified for IBR between White and Black females from 2004 and 2016. Unfortunately, the gap between the groups remained constant over this 13-year period.

scholarly journals Safety and Efficacy of Four Drug Versus Three Drug Regimens Among Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-3
Author(s):  
Saad Ullah Malik ◽  
Nazma Hanif ◽  
Priyanka Kumari ◽  
Khadija Noor Sami ◽  
Chase Warner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Standard Of Care ◽  
Drug Regimen ◽  
P Value ◽  
Newly Diagnosed ◽  
Drug Regimens ◽  
Grade 3

Introduction: During recent years there has been a boom in the availability of treatments for multiple myeloma (MM). Based on the status of disease (newly diagnosed or relapsed/refractory), several regimens have successfully improved progression free survival (PFS) and overall survival (OS) in these two types of patients. Triple drug regimen is considered the current standard of care for newly diagnosed MM patients. However, with the advent of four drug regimens, some studies demonstrated a significant improvement in PFS and OS compared to standard of care where as others showed marginal to no difference. Also, it remains unclear whether the benefits of using four drug regimen outweigh the risks. Thus, the aim of our meta-analysis was to compare the efficacy and safety of four drug versus three drug regimens among newly diagnosed multiple myeloma patients. Methods: We built a PICO based search strategy using keywords like "multiple myeloma", "randomized clinical trials" and ran literature search on PubMed, Embase, Wiley Cochrane Library, Web of Science and ClinicalTrials.gov ranging from the date of inception till 16th July, 2020. A pre-validated data extraction sheet was used to extract data on PFS, OS and ≥Grade 3 hematologic adverse events at the longest follow-up. We included only randomized clinical trials (RCTs) comparing four versus three drug regimen in newly diagnosed MM patients. We excluded studies other than RCTs, studies conducted on relapsed refractory MM patients or other plasma cell dyscrasias. A generic variance weighted random effects model (DerSimonian and Laird) was used to derive hazard ratio estimates along with their 95% confidence intervals (CIs) for PFS and OS. Risk ratio along with its 95% CIs was estimated for Grade ≥3 hematologic adverse events. Heterogeneity was assessed with Cochrane Q -statistic and was quantified with I2 test (I2 &gt;50% was consistent with a high degree of heterogeneity). A pre-specified sensitivity analysis was also performed for risk of adverse events. Cochrane Collaboration's tool was used to assess the quality of included RCTs and GRADE was used to rate the quality of evidence. Results: Initial search retrieved 7622 titles. After duplicate removal, 4880 articles were left. Following initial screening, 58 articles were considered for full text review. Of these only 3 studies (n=2277) met inclusion criteria. Four drug regimens included daratumumab, bortezomib, melphalan-prednisone (D-VMP), daratumumab, bortezomib, thalidomide-dexamethasone (D-VTd) and bortezomib and melphalan prednisone and thalidomide (VMPT-VT) respectively. Whereas, three drug regimens were bortezomib, melphalan-prednisone (VMP), bortezomib, thalidomide-dexamethasone (VTd) and bortezomib, melphalan and prednisone (VMP) respectively. There was a significant improvement in PFS when 4 vs 3 drug regimens were compared in patients with newly diagnosed MM (HR: 0.53, 95% CI: 0.46-0.62, p-value:&lt;0.001, I2: 0%). Also, OS improved significantly in four drug regimen group (HR: 0.62, 95% CI: 0.51-0.76, p-value:&lt;0.001, I2: 3.5%). There was no statistically significant difference in any grade ≥3 hematologic adverse events when 4 vs 3 drug regimens were compared (RR: 1.26, 95% CI: 0.93-1.73, p-value:0.14, I2: 93%). Sensitivity analysis after removing D-VTd regimen from any grade ≥3 hematologic adverse events revealed similar results (RR: 1.05, 95% CI: 0.97-1.13, p-value:0.23, I2: 23%) confirming the robustness of analysis. When each hematologic adverse event was looked at separately, there was no difference between 4 vs 3 drug regimen in rates of anemia (RR: 0.99, 95% CI: 0.76-1.28, p-value:0.92, I2: 0%), neutropenia (RR: 1.39, 95% CI: 1.00-1.94, p-value:0.05, I2: 85%) and thrombocytopenia (RR: 1.13, 95% CI: 0.92-1.39, p-value:0.24, I2: 33%). There was low risk of bias and strength of evidence was of moderate. Conclusion: Using four drug regimens, compared to three drug regimens, significantly improves PFS and OS among newly diagnosed multiple myeloma patients without any difference in the risk of ≥3 grade hematologic adverse events. Further randomized clinical trials are required to establish four drug regimen as standard of care for patients with newly diagnosed multiple myeloma. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

scholarly journals Treatment dilemma for survivors of rituximab-induced bowel perforation in the setting of post-transplant lymphoproliferative disorder

2018 ◽  
Vol 11 (1) ◽  
pp. e226666 ◽  
Author(s):  
Brianne J Sullivan ◽  
Grace J Kim ◽  
Gabriel Sara
Keyword(s):  
Monoclonal Antibody ◽  
Stem Cell ◽  
Lymphoproliferative Disorder ◽  
Stem Cell Transplant ◽  
Bowel Perforation ◽  
Standard Of Care ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Tumour Lysis ◽  
Post Transplant

Post-transplant lymphoproliferative disorder (PTLD) is a recognised complication of solid and haematopoietic stem cell transplant. It consists of a heterogeneous group of lymphoid neoplasms that arises secondary to post-transplant immunosuppression. Although there is no definite standard of care for the optimal treatment for PTLD, rituximab, a monoclonal antibody, with and/or without chemotherapy (usually CHOP=cytoxan, doxorubicin, vincristine, prednisone) has become a routine part of the treatment of any CD20 (+) PTLD, with response rates similar to chemotherapy with decreased toxicity. A rare and often lethal, complication of rituximab therapy for PTLD is bowel perforation secondary to tumour lysis of lymphoma involving the intestine. A small number of cases of bowel perforation have been reported, with very few documented survivors. The risk for recurrent perforation in the setting of ongoing rituximab treatment is unknown. There is sparse data supporting how to best treat the survivors.

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