scholarly journals Real-World Outcomes in Adolescents and Young Adults with Acute Lymphoblastic Leukemia without Access to Allogeneic Stem Cell Transplant

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4373-4373
Author(s):  
Sapna Pathak ◽  
Bradley W. Christensen ◽  
Radhika Kainthla ◽  
Hsiao C. Li ◽  
Navid Sadeghi
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Lymphoblastic Leukemia ◽  
Cohort Analysis ◽  
Safety Net ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Allogeneic Transplant ◽  
Patients Âgés ◽  
Safety Net Hospital

Abstract Introduction: Adolescents and young adult (AYA) patients (ages 15-39) with acute lymphoblastic leukemia (ALL) have inferior outcomes and increased treatment-related toxicity when compared to children. The use of pediatric-inspired protocols has resulted in improved outcomes in the AYA population but outcomes remain inferior to their pediatric counterparts. Hispanic patients with ALL also have inferior outcomes compared to non-Hispanic White patients. Real-world outcomes in AYA ALL patients without access to allogeneic transplant are not known, especially in Hispanic/Latino populations. Thus, in order to understand treatment outcomes with modern chemotherapy regimens in this high-risk population, we conducted a retrospective cohort analysis of all AYA ALL patients without access to allogeneic stem cell transplant at a large safety-net hospital. Methods: We conducted a retrospective single-center cohort analysis of ALL patients ages 18 to 39 treated at a large safety-net hospital in Dallas, TX between January 2010 and May 2021. All patients who received induction and consolidation at Parkland Health and Hospital System and did not receive an allogeneic stem cell transplant were included. We interrogated the database for demographic, laboratory, cytogenetic, and next-generation sequencing (using the Foundation Medicine platform) information as well as treatment outcomes and post-relapse therapy. Chemotherapy consisted of either Hyper-CVAD (+/- TKI) or the CALGB 10403 protocol. Data were stored in the RedCap database and SPSS analytical software was used to generate survival analysis and Kaplan-Meier plots. Results: We identified 54 AYA ALL patients during the designated time period, consisting of 36 males and 18 females. The median age of the cohort was 28 years, and 81% of patients were Hispanic. Twelve patients were Ph(+) and 42 patients were Ph(-); 11/12 Ph(+) patients received a TKI with induction and one patient received a TKI beginning with consolidation. Cytogenetic/FISH testing and next-generation sequencing (NGS) were performed in 42 (78%) and 13 (24%) patients respectively, with the most common aberrations noted in Table 1. Of note, NGS was not routinely performed before 2017 at our institution. Six of the 13 patients with NGS results available had Ph-like mutation signatures. The most common induction regimens used were CALGB 10403 (65%), Hyper-CVAD (15%), and Hyper-CVAD + TKI (20%). Forty-one of 49 patients (84%) with a documented day 30 bone marrow biopsy achieved a CR or CR with incomplete count recovery after induction which included 11/12 (92%) Ph(+) patients, 24/31 (77%) Ph(-) patients, and 6/6 (100%) Ph-like patients. Of the patients in CR or CRi at day 30, 27 (50%) were negative for minimal residual disease (MRD) by flow cytometry. Overall survival at 3 years for the entire cohort was 69%, and there was no statistical difference between Ph(+) and Ph(-) patients. Three-year OS was improved in patients who received Hyper-CVAD + TKI (78%) or CALGB 10403 (65%) compared to those who received Hyper-CVAD alone (59%) though this did not reach statistical significance (p=0.72). Conclusions: Our results underscore the ongoing outcomes disparities in the AYA and Hispanic populations, even with the use of modern pediatric-inspired and TKI-containing regimens. The 69% 3-year OS in our population is similar to that in the transplant-eligible AYA population and suggests a diminishing role for allogeneic transplant with current protocols. The high rate of Ph-like signatures on NGS in our population is consistent with the increased prevalence of these mutations in Hispanic ALL patients. Our study is limited as it is a retrospective analysis with a small sample size and represents the results of a single institution. Prospective studies are needed to determine the role of allogeneic transplant in Ph(+) and Ph-like AYA with ALL, and concerted efforts should be made to enroll Hispanic patients in these clinical trials given their high-risk biology and inferior outcomes. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Rare Case of Chronic Myelogenous Leukemia Presenting as T-Cell Lymphoblastic Crisis

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Parikshit Padhi ◽  
Margarita Topalovski ◽  
Radwa El Behery ◽  
Eduardo S. Cantu ◽  
Ramadevi Medavarapu
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Chronic Myelogenous Leukemia ◽  
Stem Cell Transplant ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant

Chronic Myelogenous Leukemia in blast crisis can manifest as either myeloid (more common) or lymphoid blast crisis. Most lymphoblastic crises are of B-cell lineage. T-cell blast crisis is extremely rare, with only a few reported cases. We present a case of a middle-aged man who was diagnosed with CML on peripheral blood and bone marrow biopsy. Because of a generalized lymphadenopathy noted at the time of diagnosis, a lymph node biopsy was also performed, which revealed a T-cell lymphoblastic leukemia/lymphoma, BCR/ABL1 positive, with clonal evolution. This is a very rare manifestation of CML in blast crisis with no standard treatment and with poor outcomes despite chemotherapy or allogeneic stem cell transplant. Given its rarity, it would be difficult to develop standard chemotherapy protocols. We believe the treatment for this condition should be similar to any lymphoid blast crisis. The patient was treated with induction chemotherapy (hyper-CVAD regimen) plus dasatinib for 3 cycles followed by sibling-donor allogeneic stem cell transplant and is currently on maintenance dasatinib and has minimal residual disease at this time.

Impact of autologous stem cell transplant utilization in a vulnerable multiple myeloma population.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20556-e20556
Author(s):  
Tamer Othman ◽  
Yingyu Wang ◽  
Shelly Gupta ◽  
Daniel Wu ◽  
Rohan Gupta ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Underserved Populations ◽  
Survival Rates ◽  
Safety Net ◽  
Autologous Stem Cell Transplant ◽  
Referral Process ◽  
Cell Transplant ◽  
Safety Net Hospital

e20556 Background: Despite improvements in the survival of multiple myeloma (MM) patients, disparities in outcomes persist in underserved populations, in part due to variable access to treatments including autologous stem cell transplant (ASCT), a standard treatment for fit patients. Harbor-UCLA Medical Center (HUMC) is a safety net hospital in Los Angeles with a population of socially and medically vulnerable patients, many of whom possess limited English proficiency. Historically, access to ASCT at tertiary centers has been challenging for patients at HUMC. We present the outcomes for 160 newly diagnosed MM patients between 1998 and 2019 during which our referral process for ASCT markedly improved. Methods: We retrospectively analyzed 160 MM patients evaluated at HUMC between 1998 and 2019. The cohort was divided into 2 groups based on year of diagnosis: 1998-2013 and 2014-2019. Referral for and utilization of ASCT, and 5-year survival rates were recorded. Survival rates were calculated through a Kaplan-Meier analysis. Results: 160 MM patients were included in the analysis. 93 patients were diagnosed in 1998-2013 and 64 in 2014-2019. Three patients had an unknown diagnosis date. Patient characteristics are described in Table. ASCT referrals increased from 23% to 59% (P<0.001) after designating a nurse practitioner to coordinate referrals, and implementing a standardized referral template and an electronic medical record system to send and track requests. With an increased referral rate, ASCT utilization showed an increasing trend from 15% between 1998-2013 to 27% between 2014-2019 (P=0.11). Five-year survival rate was 49% (95% CI, 37.8%-62.5%) from 1998-2013 and 70% (95% CI, 57.5%-84.6%) from 2014-2019, and was greater in patients who received ASCT compared to those who did not, 95% (95% CI, 85.2%-100.0%) versus 55% (95% CI, 40.2%-75.1%) (P=0.01). Conclusions: Increased ASCT utilization was associated with improved survival in our underserved MM population, suggesting that adherence to the most evidence-based treatments, such as ASCT utilization, may help overcome the disadvantages of a resource-limited setting. Continued refinements in our referral process will likely increase ASCT utilization. [Table: see text]

Phase II Study of Combination of hyperCVAD with Dasatinib in Frontline Therapy of Patients with Philadelphia Chromosome (Ph) Positive Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2921-2921 ◽  
Author(s):  
Farhad Ravandi ◽  
Deborah Thomas ◽  
Hagop Kantarjian ◽  
Stefan Faderl ◽  
Charles Koller ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase Ii ◽  
Stem Cell Transplant ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
High Dose ◽  
Molecular Response ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Platelet Recovery

Abstract Background: Combination of cytotoxic chemotherapy with imatinib has improved the outcome for patients with Ph+ ALL with durable remissions in some patients without an allogeneic stem cell transplant. The dual Src and Abl inhibitor dasatinib has significant clinical activity in patients with imatinib-resistant lymphoid blast phase CML and Ph+ ALL. Methods: In this phase II trial, patients with newly diagnosed Ph+ ALL receive dasatinib 50 mg po bid (or 100 mg daily) for the first 14 days of each of 8 cycles of alternating hyperCVAD and high dose cytarabine plus methotrexate. Patients (pts) in CR continue to receive maintenance dasatinib 50 mg po bid (or 100 mg daily) and vincristine and prednisone monthly for 2 years followed by dasatinib indefinitely. Minimal residual disease (MRD) monitoring is conducted and patients may receive early and late intensifications depending on their MRD status. Results: To date 22 pts with untreated Ph+ ALL and 6 pts with 1 prior cycle of chemotherapy (before Ph+/BCR-ABL+ status was known) have received a median of 6 cycles (range 1–8); 9 pts are receiving maintenance in CR. Median age is 52 years (range 21 – 79); 16 pts were older than 50 years. Median WBC at diagnosis was 20.5 ×109/L (range, 1.6 –275 × 109/L). 5 pts had CNS involvement at presentation. All pts are evaluable for assessment of response; 26 (93%) achieved CR after 1 cycle. Two pts died before response assessment from infections; in both pts, bone morrow exam on day 14 showed no detectable disease. Twenty one of 26 (81%) evaluable pts achieved cytogenetic (CG) CR after 1 cycle; 2 had a major CG response (5% and 15% Ph+), 2 had insufficient metaphases, and one is unknown (no CG exam on day 21 marrow); 1 pt developed a pseudodiploid clone. To date, 14 pts (50%) have achieved complete molecular remission (CMR) and 5 (18%) have achieved a major molecular response (MMR) at a median of 10 weeks from initiation of treatment (range 2 – 46 weeks). MRD assessment by flow cytometry is negative in 22 (85%) pts at a median of 3 weeks (range, 2–17 weeks). The median time to neutrophil and platelet recovery for cycle 1 is 18 and 23 days and for subsequent cycles is 15 and 20 days, respectively. Grade ≥3 toxicity has included 13 episodes of bleeding (8 GI, 2 GU, 1 soft tissue hematoma and 2 subdural hematomas), 3 episodes of pleural effusions, infections, diarrhea, hypophosphatemia, hypocalcemia, elevated transaminases, and reversible rise in creatinine unrelated to treatment. With a median follow up of 10 months (range, 2–21), 21 pts are alive and 18 are in CR; 2 died at induction, 3 pts died in CR; 1 from an unrelated cardiac event and 2 from infections. 5 pts have relapsed (response durations were 54, 48, 47, 32, and 22 weeks) and 2 of them have died. In 2 pts morphological relapse was preceded by flow and molecular relapse. Four relapsed pts developed new ABL mutations (3 T315I and 1 F359V). One patient has undergone an allogeneic stem cell transplant. Conclusions: The combination of hyperCVAD with dasatinib is effective in achieving molecular remissions in patients with Ph+ ALL. There is a high incidence of T315I ABL mutation among the relapsed patients.

Final Report Of Single-Center Study Of Chemotherapy Plus Dasatinib For The Initial Treatment Of Patients With Philadelphia-Chromosome Positive Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3914-3914
Author(s):  
Farhad Ravandi ◽  
Susan O'Brien ◽  
Rebecca Garris ◽  
Stefan H. Faderl ◽  
Deborah A. Thomas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Allogeneic Stem Cell Transplant

Abstract Background The dual Src and Abl inhibitor dasatinib has significant in vitro kinase inhibition against wild-type and mutant BCR-ABL, and significant clinical activity in patients with imatinib-resistant lymphoid blast phase CML (CML-LB) and Philadelphia-chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Aim To determine the long-term efficacy of the combination of the hyperCVAD regimen with dasatinib for treating patients with Ph+ ALL. Methods In this phase II trial, patients with newly diagnosed Ph+ ALL received dasatinib 50 mg po bid (or 100 mg daily) for the first 14 days of each of 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate (induction/consolidation cycles). After 42 patients, the protocol was amended to give dasatinib 100 mg daily in the first 14 days of the first cycle and then 70 mg daily continuously from the second cycle. Patients in complete remission (CR) continued to receive maintenance dasatinib 50 mg po bid (or 100 mg daily) and vincristine and prednisone monthly for 2 years followed by dasatinib indefinitely. Patients eligible for allogeneic stem cell transplant proceeded to it in first CR. Results 63 patients with untreated Ph+ ALL and 9 patients with 1 or 2 prior cycles of chemotherapy (before Ph+/BCR-ABL+ status was known) have been enrolled in the study from September 2006 to March 2012. Patients have received a median of 6 cycles (range 1-8) of induction/consolidation. Median age is 55 years (range 21 – 80); 46 patients were older than 50 years, Median WBC at diagnosis was 12 x 109/L (range, 0.4 - 658.1 x 109/L). Ten patients had CNS involvement at presentation. All patients are evaluable for assessment of response to induction; 69 (96%) achieved CR after first cycle or were CR at start. 3 patients died before response assessment from infections. 57 of 69 (83%) evaluable patients achieved cytogenetic (CG) CR after 1 cycle; 5 had a major CG response (4 had 5% and one had 15% Ph+), 2 had insufficient metaphases, and 5 are unknown (no CG exam on day 21 marrow). To date, 45 patients (65%) have achieved complete molecular remission (CMR) and another 19 (28%) have achieved a major (but not complete) molecular response (MMR) at a median of 4 weeks from initiation of treatment (range, 2 – 38 weeks). Minimal residual disease assessment by flow cytometry is negative in 65 (94 %) patients at a median of 3 weeks (range, 2-37 weeks). The median time to neutrophil and platelet recovery for cycle 1 is 18 and 22 days and for subsequent cycles is 15 and 20 days. Grade 3 and 4 adverse events have included bleeding (GI, GU, soft tissue and subdural hematomas), pleural effusions, pericardial effusions, reversible rise in creatinine, deep vein thromboses, pulmonary emboli, as well as diarrhea, infections, hypophosphatemia, hypokalemia, hypocalcemia, hyperglycemia, and elevated transaminases. With a median follow up of 48 months in the surviving patients (range 16.5 - 81.5), 36 patients (50%) are alive and 31 (43%) are in CR. Twelve patients have undergone an allogeneic stem cell transplant. Thirty six patients have died [3 at induction, 16 after relapse, 7 post stem cell transplant performed in CR1, and 10 in CR (6 from infections, 1 from unrelated cardiac event, 1 from unrelated cancer, and 2 from an unknown cause)]. The median disease free survival is 31 months (range, 0.3 to 81) and the median overall survival is 44 months (range, 0.2 to 82). Twenty-one patients have relapsed with a median response duration of 16 months (range, 5 - 62) and 16 of them have died. In 6 patients morphological relapse was preceded by flow and molecular relapse. Six relapsed patients had ABL mutations (4 T315I, 1 F359V, and 1 V299L). Conclusion Combination of chemotherapy with dasatinib is effective in achieving long term remissions in patients with newly diagnosed Ph+ ALL. Disclosures: Ravandi: Bristol Myers Squibb: Honoraria, Research Funding. Off Label Use: Use of dasatinib for the frontline therapy of Ph+ ALL. O'Brien:Pharmacyclics: Research Funding. Jabbour:Bristol Myers Squibb: Consultancy, Honoraria. Cortes:Bristol Myers Squibb: Research Funding. Kantarjian:Bristol Myers Squibb: Research Funding.

Sign in / Sign up

Export Citation Format

Share Document