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Blood Advances Feb 2024Outcomes in patients with relapsed diffuse large B-cell lymphoma (DLBCL) who undergo autologous stem cell transplant (auto-SCT) are poor. Blinatumomab is a CD3/CD19...
Outcomes in patients with relapsed diffuse large B-cell lymphoma (DLBCL) who undergo autologous stem cell transplant (auto-SCT) are poor. Blinatumomab is a CD3/CD19 bispecific T-cell engager that directs cytotoxic T cells to CD19+ cells. Here, we performed a pilot study of blinatumomab consolidation after auto-SCT for 14 patients with DLBCL or transformed follicular lymphoma. All patients underwent standard-of-care auto-SCT with carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning followed by 1 cycle (4 weeks continuous infusion) of blinatumomab consolidation starting at day 42 after auto-SCT. All 14 patients treated on study completed BEAM auto-SCT and 1 cycle of posttransplant blinatumomab. Five patients developed grade 1 cytokine release syndrome (CRS), with no grade 2 or higher CRS. Immune effector cell-associated neurotoxicity syndrome was not observed. Patients were followed up for 3 years after auto-SCT, with median follow-up of 37 (range, 12-65) months. One-hundred days after auto-SCT (1 month after blinatumomab consolidation), 12 patients (86%) had achieved complete remission. At 1 year after auto-SCT, 7 patients (50%) remained in CR, and 1 patient had died of progressive disease. Patients who relapsed had a lower CD8:CD4 T-cell ratio before starting blinatumomab than patients who remained in remission. This pilot study demonstrates blinatumomab consolidation after auto-SCT is safe and well tolerated. Strategies to increase the CD8:CD4 ratio and use additional cycles of consolidation in a larger randomized trial are needed to confirm the efficacy of consolidation with blinatumomab after auto-SCT. This trial was registered at www.clinicaltrials.gov as #NCT03072771.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Pilot Projects; Remission Induction; Transplantation, Autologous; Neoplasm Recurrence, Local; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Stem Cell Transplantation; Antibodies, Bispecific
PubMed: 37871306
DOI: 10.1182/bloodadvances.2023011130 -
Transplantation and Cellular Therapy Jan 2024Juvenile myelomonocytic leukemia (JMML), which is classified as a myelodysplastic/myeloproliferative neoplasm, is a rare hematologic malignancy of childhood. Most...
Juvenile myelomonocytic leukemia (JMML), which is classified as a myelodysplastic/myeloproliferative neoplasm, is a rare hematologic malignancy of childhood. Most patients with JMML require allogeneic hematopoietic cell transplantation (HCT) as a curative therapy. A Japanese retrospective analysis demonstrated favorable outcomes for a busulfan (BU) + fludarabine (FLU) + melphalan (MEL) regimen, with an overall survival (OS) of 72% and an event-free survival (EFS) of 53%. To further validate the efficacy and safety of this regimen, the Japan Pediatric Leukemia/Lymphoma Study Group (JPLSG) conducted a nationwide prospective study, JMML-11. Between July 2011 and June 2017, 28 patients with newly diagnosed JMML were enrolled in JMML11. Low-dose chemotherapy for tumor control before HCT was recommended, and patients treated with AML-type chemotherapy and azacitidine were excluded. The conditioning regimen comprised i.v. BU, 16 doses administered every 6 h, with dose adjustment based on pharmacokinetic (PK) studies on days -11 to -8; FLU, 30 mg/m/day or 1 mg/kg/day for patients <10 kg or age <1 year on days -7 to -4; and MEL, 90 mg/m/day or 3 mg/kg/day for patients <10 kg or <1 year on days -3 to -2. The donor was selected by the physician in charge. A family donor was available for 7 patients (3 HLA-matched siblings, 3 HLA-1-antigen mismatched parents, and 1 haploidentical father). Overall, 21 patients received grafts from unrelated donors, including 8 HLA-matched donors and 13 HLA-mismatched donors. The graft source was related bone marrow (BM) for 7 patients, unrelated BM for 14 patients, and unrelated cord blood for 7 patients. Neutrophil engraftment was achieved in 21 of 28 patients (75%), with a median of 20.5 days (range, 11 to 39 days) after transplantation. The 3-year OS, 3-year EFS, 3-year relapse rate, and 3-year transplantation-related mortality were 63% (95% confidence interval [CI], 42% to 78%), 52% (95% CI, 32% to 69%), 18% (95% CI, 6% to 34%), and 21% (95% CI, 9% to 38%), respectively. WBC count before the conditioning regimen (≥7.0 × 10/L) was significantly associated with inferior EFS and OS. Body surface area ≥.5 m, spleen size <4 cm before conditioning, and HLA-matched unrelated BM donors were significantly associated with better OS. Adverse effects related to the conditioning regimen included febrile neutropenia (86%), diarrhea (39%), hypoxemia (21%), and mucositis (18%). BU-associated toxicity, including sinusoidal obstruction syndrome (SOS) and thrombotic microangiopathy (TMA), occurred in 7 patients (25%; SOS, n = 6; TMA, n = 2). Retrospective analysis of PK data after the first BU dose in 23 patients, including 6 with SOS and 17 without SOS, did not show significant differences between groups. The JMML-11 study confirms the positive results of previous retrospective analyses. BU+FLU+MEL might become a standard conditioning regimen for patients with JMML.
Topics: Child; Humans; Busulfan; Hematopoietic Stem Cell Transplantation; Japan; Leukemia, Myelomonocytic, Juvenile; Lymphoma; Melphalan; Prospective Studies; Retrospective Studies; Transplantation, Homologous
PubMed: 37806448
DOI: 10.1016/j.jtct.2023.10.002 -
Frontiers in Immunology 2024Melphalan is the most common conditioning regimen used prior to autologous stem cell transplant (ASCT); however, there are varying data on optimal melphalan timing prior...
BACKGROUND
Melphalan is the most common conditioning regimen used prior to autologous stem cell transplant (ASCT); however, there are varying data on optimal melphalan timing prior to transplant for best safety and efficacy. Historically, ASCT conditioning consisted of melphalan 200 mg/m on day 2 (D-2) (48 h prior to ASCT), but many institutions have since adopted a melphalan protocol with administration on day 1 (D-1) (24 h prior to SCT) or split dosing over the 2 days. The optimal timing of melphalan has yet to be determined.
METHODS
In this single-center retrospective study, we analyzed transplant outcomes for patients between March 2011 and September 2020 admitted for high-dose, single-agent melphalan 200 mg/m on D-1 vs. D-2. The primary outcomes were time to neutrophil and platelet engraftment. Secondary outcomes include incidence of hospital readmission within 30 days, 2-year progression-free survival, and 2-year overall survival.
RESULTS
A total of 366 patients were studied (D-2 n = 269 and D-1 n = 97). The incidence of high-risk cytogenetics was similar between the two groups (37% vs. 40%). Median days to absolute neutrophil count engraftment was similar at 11 days in the D-2 and D-1 cohort (n = 269, range 0-14, IQR 11-11 vs. n = 97, range 0-14, IQR 11-12). Median days to platelet engraftment >20,000/mcL was 18 days for D-2 melphalan (range: 0-28, IQR 17-20) versus 19 days for D-1 melphalan (range: 0-32, IQR 17-21). Overall survival at 2 years post-transplant was similar in both cohorts (94%; p = 0.76), and PFS was 70% in D-2 compared with 78% in D-1 (p = 0.15). In a multivariable model including age and performance status, hospital readmission within 30 days of transplant was higher in the D-1 cohort (odds ratio 1.9; p = 0.01).
CONCLUSION
This study demonstrates similar neutrophil and platelet engraftment in D-1 and D-2 melphalan cohorts with similar 2-year PFS and OS. Either D-2 or D-1 melphalan dosing schedule is safe and effective.
Topics: Humans; Multiple Myeloma; Melphalan; Retrospective Studies; Stem Cell Transplantation
PubMed: 38504993
DOI: 10.3389/fimmu.2024.1310752 -
Cancer Imaging : the Official... Jul 2023Percutaneous hepatic perfusion (PHP) is a palliative intraarterial therapy for unresectable hepatic malignancies. During PHP, high-dose melphalan is infused via the...
PURPOSE
Percutaneous hepatic perfusion (PHP) is a palliative intraarterial therapy for unresectable hepatic malignancies. During PHP, high-dose melphalan is infused via the hepatic artery to saturate tumor in the liver with the chemotherapeutic substance. The venous hepatic blood is filtered by an extracorporeal melphalan specific filtration system. Blood clotting in the extracorporeal filter system is prevented by administering unfractionated heparin (UFH) in high doses, which might be reversed with protamine sulfate after the procedure. Aim of this retrospective two-center-study was to analyze the potential effect of UFH reversal with protamine sulfate on complication rates following PHP.
MATERIALS AND METHODS
All patients receiving PHP treatment between 10/2014 and 04/2021 were classified according to their intraprocedural coagulation management: 92 patients/192 PHP received full UFH reversal with protamine (group); 13 patients/21 PHP in group received a reduced amount of protamine, and 28 patients/43 PHP did not receive UFH reversal with protamine (group). Periinterventional clinical reports, findings and laboratory values were retrospectively evaluated. Complications and adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAEv5.0).
RESULTS
Thromboembolic events were recorded after 10 PHP procedures (5%) in group, six of which (3%) were major events (CTCAE grade 3-5). No (0%) thromboembolic events were recorded in group and group. Hemorrhagic events were registered after 24 PHP (13%) in group two of which (1%) were major (CTCAE grade 3-4). In group, only minor bleeding events were recorded, and one major hemorrhagic event was documented in group (2%). There was a significant difference between the percentage of post-interventional thrombopenia in group (39%) and group (14%) versus group (23%) (p=.00024). In group one patient suffered from a severe anaphylactic shock after the administration of protamine.
CONCLUSION
Our retrospective study implies that there might be a link between the practice of protamine sulfate administration to reverse the full hemodilutive effect of UFH after PHP and the post-interventional risk of thromboembolic events as well as clinically significant thrombopenia. Our data suggest that the standard use of protamine sulfate after PHP in low-risk patients without clinical signs of active bleeding should be critically re-evaluated.
Topics: Humans; Heparin; Melphalan; Retrospective Studies; Protamines; Thrombocytopenia; Perfusion
PubMed: 37452405
DOI: 10.1186/s40644-023-00590-7 -
Cardiovascular and Interventional... Apr 2024Retinoblastoma is the most common eye malignancy in children that if left untreated can invade intraocular structures, metastasize, and rarely lead to death.... (Review)
Review
Retinoblastoma is the most common eye malignancy in children that if left untreated can invade intraocular structures, metastasize, and rarely lead to death. Traditionally treated with systemic chemotherapy, Intra-arterial chemotherapy is gaining popularity as it allows for the direct administration of chemotherapy through the ophthalmic artery, thus reducing systemic side effects. Intra-arterial chemotherapy procedures have evolved, with refinements to reduce risks and radiation exposure. Intra-arterial chemotherapy boasts an impressive technical success rate and one year ocular survival even amongst advanced cases. This review offers a thorough examination of the technique, indications, contraindications, outcomes, and alternative options for Intra-arterial chemotherapy.
Topics: Child; Humans; Infant; Retinoblastoma; Retinal Neoplasms; Infusions, Intra-Arterial; Ophthalmic Artery; Radiation Exposure; Melphalan; Retrospective Studies
PubMed: 38509339
DOI: 10.1007/s00270-024-03692-2 -
Journal of Oncology Pharmacy Practice :... Sep 2023High-dose melphalan-based autologous stem cell transplant (ASCT) remains a standard of care for plasma cell disorders (PCDs). Currently, there is variability in the...
High-dose melphalan-based autologous stem cell transplant (ASCT) remains a standard of care for plasma cell disorders (PCDs). Currently, there is variability in the literature surrounding the timing of melphalan administration to avoid potential cytotoxic effects, although the administration has been safely proposed when given at least 8 hours prior to stem cell infusion. The objectives of this study were to assess differences in safety and efficacy outcomes between day -1 and day -2 single-dose melphalan administration in patients undergoing ASCT for PCDs. A retrospective chart review was performed at our institution comparing patients receiving melphalan on day -1 to an equal number of patients receiving melphalan on day -2. The primary endpoint was time to neutrophil engraftment from stem cell infusion. Univariate analyses were performed. Mean time to neutrophil engraftment from stem cell infusion was identical at 10.7 days for both cohorts ( = 0.88). Mean time to platelet engraftment from stem cell infusion was shorter with day -1 administration (17.4 vs. 18.6 days, = 0.06). Mean time to neutrophil and platelet engraftment from melphalan infusion were significantly shorter with day -1 administration. Similar outcomes were observed for length of hospitalization, infection- and mucositis-related toxicities, hematologic response, transplant-related mortality, and overall survival. Our findings show no difference in time to neutrophil engraftment from stem cell infusion and a trend toward shorter time to platelet engraftment with day -1 administration. Based on our study, day -1 melphalan administration is an acceptable and safe practice.
Topics: Humans; Melphalan; Multiple Myeloma; Retrospective Studies; Plasma Cells; Transplantation, Autologous; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning
PubMed: 36245321
DOI: 10.1177/10781552221125871 -
Hematology (Amsterdam, Netherlands) Dec 2023In Madagascar, the epidemiologic, therapeutic, and evolutionary aspects of multiple myeloma remain poorly understood. Our objectives were to describe the cases, report...
INTRODUCTION
In Madagascar, the epidemiologic, therapeutic, and evolutionary aspects of multiple myeloma remain poorly understood. Our objectives were to describe the cases, report factors associated with mortality, and estimate patient survival.
PATIENTS AND METHOD
This was a retrospective descriptive and analytical study conducted in five teaching hospitals in Madagascar: HJRA and CENHOSOA (Antananarivo), CHUPZAGA (Mahajanga), CHUAT (Toamasina) and CHUT (Fianarantsoa). The study included patients diagnosed with multiple myeloma between January 1, 2010 and December 31, 2021.
RESULTS
Of the 11,374 cancer patients, 75 (0.66%) had multiple myeloma. The mean age of the patients was 59.9 years (±8.9) and the sex ratio was 1.5. Arterial hypertension was observed in 32% of the patients. The most common symptom of myeloma was bone pain ( = 48; 64%). Forty-six patients (61%) were diagnosed with stage III myeloma and 28 patients (37.3%) with stage IIIA myeloma according to the Durie-Salmon classification. Anemia, renal failure, hypercalcemia and fractures were present in 53%, 37%, 21% and 28% of cases, respectively. Fifty-four patients received specific treatment. The combination of melphalan-prednisone-thalidomide was used in 79.63% of cases, and one patient had received autologous stem cell transplantation. Eleven patients (14.67%) died. Chronic kidney disease ( = 0.009), smoking ( = 0.028) and two associated comorbidities ( = 0.035) were associated with mortality. The median overall survival was 45.5 months.
CONCLUSION
Patient survival is shorter than reported in the literature. The high mortality rate is due to comorbidities and limited access to recommended therapies.
Topics: Humans; Middle Aged; Multiple Myeloma; Madagascar; Hematopoietic Stem Cell Transplantation; Retrospective Studies; Transplantation, Autologous
PubMed: 37746751
DOI: 10.1080/16078454.2023.2261803 -
Cytotherapy May 2024The combination therapy of autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CART) therapy has been employed to improve...
Prognostic differences between carmustine, etoposide, cytarabine and melphalan (BEAM) and carmustine, etoposide, cytarabine, melphalan and fludarabine (BEAMF) regimens before autologous stem cell transplantation plus chimeric antigen receptor T therapy in patients with refractory/relapsed B-cell...
BACKGROUND AIMS
The combination therapy of autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CART) therapy has been employed to improve outcomes for relapsed or refractory (R/R) B-cell non-Hodgkin-lymphoma (B-NHL). The widely used conditioning regimen before ASCT plus CART therapy reported in the literature was carmustine, etoposide, cytarabine and melphalan (BEAM). However, whether adding fludarabine to the BEAM regimen (BEAMF) can improve the survival of patients with R/R B-NHL remains unknown.
METHODS
In total, 39 and 19 patients with R/R B-NHL were enrolled to compare clinical outcomes in the BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy, respectively.
RESULTS
The objective response (OR) rates at 3 months to BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy were 71.8% and 94.7%, respectively (P = 0.093). The BEAMF regimen showed a trend towards a superior duration of response compared with the BEAM regimen (P = 0.09). After a median follow-up of 28 months (range: 0.93-51.9 months), the BEAMF regimen demonstrated superior 2-year progression-free survival (PFS) (89.5% versus 63.9%; P = 0.048) and 2-year overall survival (OS) (100% vs 77.3%; P = 0.035) compared with the BEAM regimen. In the multivariable Cox regression analysis, OR at month 3 (responders) was remarkably correlated with better OS (hazard ratio: 0.112, P = 0.005) compared with OR (non-responders).
CONCLUSIONS
For patients with R/R B-NHL, the BEAMF regimen before ASCT plus CD19/22 CART therapy was correlated with superior PFS and OS than the BEAM regimen, and the BEAMF regimen is a promising alternative conditioning regimen for ASCT plus CAR-T therapy.
Topics: Humans; Male; Carmustine; Melphalan; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Middle Aged; Adult; Transplantation, Autologous; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Vidarabine; Prognosis; Aged; Lymphoma, B-Cell; Podophyllotoxin; Immunotherapy, Adoptive; Young Adult; Combined Modality Therapy; Transplantation Conditioning; Receptors, Chimeric Antigen
PubMed: 38385909
DOI: 10.1016/j.jcyt.2024.01.012 -
Journal of Veterinary Internal Medicine 2024Myeloma-related disorders (MRDs) are rare and poorly documented neoplasms of cats.
BACKGROUND
Myeloma-related disorders (MRDs) are rare and poorly documented neoplasms of cats.
HYPOTHESIS/OBJECTIVES
To describe clinical, clinicopathologic, and imaging findings, response to treatment, and survival time and to identify factors associated with shorter outcomes in cats with MRD.
ANIMALS
Fifty cats with a diagnosis of MRD.
METHODS
Cats with paraproteinemia confirmed by serum protein electrophoresis (SPE) and either intramedullary plasmacytosis >10%, marked cytonuclear atypia with intramedullary plasmacytosis that ranged between 5% and 10%, or cytologically or histologically confirmed visceral infiltration were retrospectively included from several veterinary referral centers.
RESULTS
Bone marrow plasmacytosis and splenic or hepatic involvement were present in 17/27 cats (63%), 36/42 cats (86%), and 27/38 cats (71%), respectively. Anemia was reported in 33/49 cats (67%) and thrombocytopenia in 16/47 cats (34%). Some of the treatments that the cats received included melphalan and prednisolone (n = 19), cyclophosphamide and prednisolone (n = 10), chlorambucil and prednisolone (n = 4), prednisolone (n = 4), or other (n = 4). The overall response rates to melphalan, cyclophosphamide, and chlorambucil in combination with prednisolone were 87%, 90%, and 100%, respectively. Adverse events to melphalan or cyclophosphamide occurred in 65% and 23% of cats, respectively. Median survival time was 122 days (range, 0-1403) and was not significantly associated with chemotherapy protocol. Anemia (hazard ratio [HR], 3.1; 95% confidence interval [CI], 1.0-9.8) and thrombocytopenia (HR, 2.7; 95% CI, 1.2-6.0) were risk factors for shorter survival.
CONCLUSIONS AND CLINICAL IMPORTANCE
Our study confirmed the guarded prognosis of MRD in cats and identified risk factors for shorter survival times.
Topics: Cats; Cat Diseases; Animals; Retrospective Studies; Female; Male; Multiple Myeloma; Prognosis; Melphalan; Prednisolone; Cyclophosphamide; Anemia
PubMed: 38517293
DOI: 10.1111/jvim.17051 -
American Journal of Hematology Feb 2024Improvement of autologous stem-cell transplantation (ASCT) for myeloma is needed. Building on our prior work, we prospectively evaluated panobinostat and...
Safety and efficacy of a new high-dose regimen of panobinostat, gemcitabine, busulfan, and melphalan for 1st or 2nd salvage ASCT for refractory/relapsed or high-risk myeloma: Matched-pair comparisons with concurrent control cohorts.
Improvement of autologous stem-cell transplantation (ASCT) for myeloma is needed. Building on our prior work, we prospectively evaluated panobinostat and gemcitabine/busulfan/melphalan (GemBuMel) with ASCT in this population. Patients aged 18-65 years with relapsed/refractory or high-risk myeloma and adequate end-organ function were eligible. Treatment included panobinostat (20 mg/day, days -9 to -2) and GemBuMel (days -8 to -2). Patients were enrolled in 1st (ASCT-1) or 2nd ASCT (ASCT-2) cohorts. We compared their outcomes with all our other concurrent ASCT patients who met eligibility criteria but received melphalan or BuMel off study, matched for age, prior therapy lines, high-risk cytogenetics, and response at ASCT. We enrolled 80 patients, 48 and 32 in the ASCT-1 and ASCT-2 cohorts, respectively; in these two cohorts, high-risk cytogenetics were noted in 33 and 15 patients, respectively; unresponsive disease in 12 and 11 patients, respectively, after a median of 2 and 3 therapy lines, respectively. Transplant-related mortality (TRM) occurred in two ASCT-2 patients. One-year PFS rates were 69% (ASCT-1) and 72% (ASCT-2); 1-year OS rates were 79% (ASCT-1) and 84% (ASCT-2). Minimal residual disease negativity improved after ASCT-1 (8.5%-23%, p < .0001) and ASCT-2 (34%-55%, p = .02), which correlated with improved outcomes. Trial patients and controls (N = 371) had similar TRM and post-ASCT maintenance. Trial patients had better PFS after either a 1st (p = .02) or a 2nd ASCT (p = .04) than matched-paired control patients. In conclusion, panobinostat/GemBuMel is effective for relapsed/refractory or high-risk myeloma patients, with better PFS than concurrent matched controls receiving melphalan or BuMel.
Topics: Humans; Melphalan; Multiple Myeloma; Gemcitabine; Busulfan; Panobinostat; Hematopoietic Stem Cell Transplantation; Transplantation, Autologous; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38100199
DOI: 10.1002/ajh.27168