Characteristics and Outcomes of 38 Patients with Acute Myeloid Leukemia Evolving from Previous Well Characterized Myeloproliferative Disorder.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2705-2705
Author(s):  
Constantine S. Tam ◽  
Francis Giles ◽  
Jorge Cortes ◽  
Guillermo Garcia-Manero ◽  
Elihu Estey ◽  
...  
Keyword(s):  
Stem Cell ◽  
Induction Chemotherapy ◽  
Supportive Therapy ◽  
Myeloproliferative Disorders ◽  
Complete Response ◽  
Cancer Center ◽  
High Dose ◽  
Cell Transplant ◽  
Radioactive Phosphorus ◽  
Poor Risk

Abstract Antecedent hematological disorder (AHD) is a known adverse prognostic factor for patients with AML. AHD, however, encompasses a range of diverse hematological disorders. The characteristics and outcome of AML evolving from myeloproliferative disorders (MPD) without features of dysplasia remain poorly defined. Between 08/73 and 01/06, 76 patients were treated at the MD Anderson Cancer Center for AML evolving from a previous MPD. Of these, 38 were excluded from further analyses: inadequate pathological information for confident diagnosis of MPD (n=15), concomitant myelodysplastic features (n=11), chronic myelomonocytic leukemia (n=4), and less than twelve months between MPD diagnosis and AML occurrence (n=8). Baseline characteristics of remaining 38 patients with well-characterized MPD: median age 51 years (range 24–70); male 61%; cytogenetics - diploid 86%, del20q 14%; splenomegaly 27%. Diagnoses by WHO classification: polycythemia vera 47%; myelofibrosis 24%; essential thrombocythemia 18%; chronic MPD unclassifiable 11%. MPD therapy: hydroxyurea in 87% (median 3 years exposure), alkylating agent in 16%, and radioactive phosphorus in 8% of patients. AML occurred a median of 111 months (range 22 – 376) after MPD diagnosis. Median age at AML diagnosis was 65 years (range 40–81); cytogenetics were poor risk (−5, −7, 11q23, or ≥3 abnormalities) in 50% and intermediate risk in others (including diploid in 28%). Median survival was 23 weeks after AML diagnosis, and was not significantly different between patients who received AML therapy and those who received supportive therapy only (p=0.33) (figure 1), or between patients with intermediate and poor risk cytogenetics (p=0.12). Twenty-four patients received standard or high-dose Ara-C based induction chemotherapy: complete response (CR) rate was 38%, but responses were short-lived with all patients relapsing within 37 weeks in the absence of stem cell transplantation. Two patients underwent non-myeloablative matched sibling stem cell transplant in first CR: one remain leukemia free at 70 weeks, and the second relapsed 22 weeks post transplant but responded to re-induction chemotherapy, and remains alive at 38 weeks. AML evolving from a previous MPD carries an adverse prognosis, with very poor results from conventional induction chemotherapy. Exploration of novel agents in this patient population as a first line therapy is warranted. Figure Figure

The Mitochondrial Metabolism Inhibitor Cpi-613 in Combination with High Dose Ara-C (HDAC) and Mitoxantrone Is Highly Active in Poor Risk Relapsed or Refractory Acute Myeloid Leukemia (AML)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2556-2556
Author(s):  
Timothy Pardee ◽  
Kristin Pladna ◽  
Scott Isom ◽  
Leslie Renee Ellis ◽  
Dmitriy Berenzon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Survival ◽  
Response Rate ◽  
Residual Disease ◽  
Single Agent ◽  
High Dose ◽  
Cell Transplant ◽  
Historical Cohort ◽  
Poor Risk ◽  
Equity Ownership

Abstract Background: CPI-613 is a first in class agent that inhibits pyruvate dehydrogenase (PDH) and α-ketogluterate dehydrogenase. As a single agent CPI-613 was found to be well tolerated with possible activity in several patients with myeloid malignancies.This trial determined the maximum tolerated dose (MTD), safety, and efficacy of CPI-613 in combination with HDAC and mitoxantrone in patients with relapsed or refractory AML. Methods: CPI-613 was given daily on days 1 through 5 starting at a dose of 500 mg/m2. Beginning on day 3, HDAC at 3,000 mg/m2 (or 1,500 mg/m2 for age ≥60) is administered every 12 hours for 5 total doses and mitoxantrone at 6 mg/m2 is given daily for 3 doses. If residual disease is present on day 14 re-induction with the same or a three day abbreviated course could be given. Patients who achieved a complete remission with or without complete count recovery (CR or CRi) could receive up to a total of two additional consolidation cycles with the goal to get responders to stem cell transplant whenever possible. Results: A total of 67 patients have been enrolled and 65 are evaluable. The median age is 60 (range 21-79). Nineteen patients had refractory disease and 14 received at least 1 previous line of salvage therapy. In patients with relapsed disease the median duration of CR1 was 5 months. Cytogenetics were poor risk in 30 patients, intermediate in 30 and good in 6. One patient had CML in myeloid blast crisis. The overall intention to treat response rate was 48% (26CR+5CRi) with a median survival of 6.4 months. In patients ≥60 years old the CR/CRi rate was 42% (15/36). Surprisingly, the response rate for patients with poor risk cytogenetics was 47% (11CR+3CRi) with a median survival of 5.2 months. In a historical cohort treated with HDAC, mitoxantrone and asparaginase at our institution, only 19% (3/16) of patients with poor risk cytogenetics responded with a median survival of 2.8 months. The MTD of CPI-613 in combination with HDAC and mitoxantrone is 2,500 mg/m2. The dose limiting toxicities were diarrhea and nausea. Nine patients (13%) died on or before day 30. The most common toxicities attributed to CPI-613 were diarrhea and nausea, mainly grade 1 or 2. At the time of this submission thirteen patients have gone on to allogeneic stem cell transplantation. Several patients with circulating blasts had blood samples taken before and after CPI-613 infusion. Three of these patients had increased phosphorylation of PDH consistent with its inhibition. Additionally, two patients demonstrated a robust phosphorylation of adenosine monophosphate-activated protein kinase consistent with depletion of ATP. To explore if loss of p53 function (common in poor risk cytogenetics) affected response we tested CPI-613 alone or with an anthracycline against an AML cell line with and without p53 knockdown. Suppression of p53 function resulted in significant resistance to the anthracycline but no change in response to CPI-613; the combination enhanced cell kill over either agent alone. Conclusions: CPI-613 in combination with HDAC and mitoxantrone is a promising salvage regimen, especially in patients with poor risk cytogenetics. Disclosures Pardee: Novartis: Speakers Bureau; Celgene: Speakers Bureau. Off Label Use: CPI-613 is a novel anticancer agent not currently approved by the FDA. Ellis:Alexion: Speakers Bureau. Manuel:Novartis: Speakers Bureau. Hurd:Merck: Equity Ownership; Pfizer: Equity Ownership; Medtronic: Equity Ownership; Procter and Gamble: Equity Ownership; Bristol Myers Squib: Equity Ownership. Powell:Celgene: Speakers Bureau; Cornerstone Pharmaceuticals: Consultancy.

scholarly journals Comparison of Two Post-Transplant Predictive Indexes: Day 100 is a Better Time-Point for Response Evaluation after Autologous Stem Cell Transplantation in Multiple Myeloma: Ass Retrospective Study

2020 ◽  
Vol 7 (8) ◽  
Author(s):  
Ma’koseh M ◽  
◽  
Sa’deh S ◽  
Halahleh K ◽  
Abu-Jazar H ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Response Evaluation ◽  
Therapeutic Implications ◽  
Significant Difference

In Multiple Myeloma (MM), response to High-Dose Chemotherapy (HDC) and Autologous Stem Cell Transplant (ASCT) has important prognostic and therapeutic implications. Best timing for response evaluation after ASCT is not well studied. Our study evaluated the correlation between response on day 30 and day 100 after ASCT with Progression Free Survival (PFS) and Overall Survival (OS) in 119 MM patients. Median follow-up was 39.8 months. Complete Response (CR) was achieved in 53.8% and 55.5% of patients on D 30 and D 100, respectively. On D30, there was no significant difference in PFS or OS in CR vs. no CR group (35.4 vs. 22.1 months, p: 0.058) and (92.6 months vs. not reached p: 0.96) respectively nor in responders (R) vs. Non-Responders (NR) group (97.8 vs. 47.1 months p: 0.08) and (30.2 vs. 18.9 months, p: 0.09) respectively. While on D100, PFS was significantly better in CR vs. no CR group (33.8 vs. 18.1 months, p: 0.0047) as well as in R vs. NR (30.6 vs. 16.9 months p: 0.015). However, OS was not better in either (92.6 vs. 52.1 months p: 0.46) and (92.6 months vs. not reached p: 0, 88) respectively. In conclusion, after HDC and ASCT for MM, we recommend doing response evaluation on D100 rather than D30 as it better correlates with PFS. Further studies are required to confirm this finding in the era of consolidation and maintenance treatment.

Role of Second Stem Cell Transplant in Patients with Amyloidosis Who Are Refractory or Relapsing.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5469-5469
Author(s):  
Morie Abraham Gertz ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Suzanne R. Hayman ◽  
Shaji K. Kumar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Light Chain ◽  
Stem Cell Transplant ◽  
Complete Response ◽  
Free Light Chain ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Therapy ◽  
Single Organ

Abstract Introduction: Stem cell transplant is an increasingly widely applied technique for managing amyloidosis. As in multiple myeloma, the treatment would not be expected to be curative and patients would be expected to relapse in most instances. In addition, approximately one-third of patients fail to respond to initial therapy. The role of second transplantation in treatment failures or patients who relapse is reviewed. Patients: Of 242 patients undergoing high dose conditioning and stem cell transplantation for amyloidosis (AL) at the Mayo Clinic, 6 subsequently underwent a second transplant. Results: Patient 1, who had single organ renal amyloid nephrotic syndrome responded and relapsed at 73 months, received a second stem cell transplant achieving a hematologic complete response with normalization of a markedly elevated pre transplant free light chain (59 to 1.9 mg/dL) and is alive at 12 months. Patient 2 relapsed 42 months after transplant for single organ renal amyloidosis; the second stem cell transplant, has normalized his free light chain ratio reduced his urinary protein loss from 5450 to 1482 mg/day and he is alive 21 months following his second transplant (63 months overall). Patient 3 relapsed 34 months after a response of renal and cardiac amyloidosis. After transplant two, he failed to achieve a 50% reduction in his free light chain, began hemodialysis 7 months post transplant and died one year post transplant. Patient 4 with single organ cardiac involvement relapsed 30 months following his first transplant and died on day +5 of his second transplant of an acute pulmonary embolus. Patient 5 was a response failure after his first transplant, had a second transplant 35 months later, having failed Dexamethasone followed by Melphalan/Dexamethasone therapy, and died 3 months later of progressive disease. Patient 6 had single organ vascular involvement manifest by calf and thigh claudication and failed to respond with his first transplant with a persistently elevated free light chain. The second transplant was performed six months after the first without further free light chain reduction and persistent claudication at 11 months. Conclusion: Patients who failed to achieve a hematologic response after a first transplant appear not to benefit from a second course of high dose therapy. Among 4 patients who were previously responsive and relapsed, one achieved a hematologic complete response, one achieved a hematologic partial response, and two died. The two patients achieving a second hematologic response had the longest response duration (73 and 42 months) following their first transplant, and the second response presumably reflects favorable (indolent; non proliferative) biology of the underlying plasma cell dyscrasia. High dose therapy and stem cell transplant may be an effective salvage regimen for patients who responded to a first transplant and whose response lasted greater than 36 months.

High-dose consolidation therapy with autologous stem cell rescue in stage IV breast cancer.

1989 ◽  
Vol 7 (12) ◽  
pp. 1824-1830 ◽  
Author(s):  
S F Williams ◽  
R Mick ◽  
R Desser ◽  
J Golick ◽  
J Beschorner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Induction Chemotherapy ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Complete Response ◽  
High Dose ◽  
Stem Cell Rescue ◽  
Stage Iv Breast Cancer ◽  
Autologous Stem Cell Rescue

We designed a phase II study to determine whether induction chemotherapy (CT) consisting of leucovorin, vincristine, methotrexate, doxorubicin, and cyclophosphamide (LOMAC) followed by high-dose intensification chemotherapy (ICT) with cyclophosphamide, thiotepa, and autologous stem cell rescue (ASCR) could increase the complete response (CR) rate and survival in women with stage IV breast cancer. Twenty-nine women were enrolled on study; 16 patients had received prior adjuvant chemotherapy and no patient had received chemotherapy for stage IV disease. Two patients were found to be ineligible and excluded from further analysis. Of the 27 patients treated, four (15%) obtained a CR and 15 (56%) a partial response (PR) after LOMAC induction, for an overall response rate of 70%. Of the 22 patients treated with ICT, 12 patients had a CR, and nine were in PR after induction and converted to CR after ICT. The toxicities included nausea/vomiting, mucositis, diarrhea, dermatitis, alopecia, and infections secondary to neutropenia. The 1-year survival is 60%; the median has not yet been reached. The time to treatment failure for patients on study is 10 months. The treatment approach of ICT and ASCR following induction chemotherapy can lead to an improved CR rate in stage IV breast cancer. How this increased CR rate leads to a prolonged disease-free survival requires further follow-up.

Comparison of Early and Late Autologous Stem Cell Transplants for Multiple Myeloma: A Single Institution Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 928-928
Author(s):  
Shaji Kumar ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Suzanne R. Hayman ◽  
S. Vincent Rajkumar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Plasma Cell ◽  
Complete Response ◽  
High Dose ◽  
Cell Transplant ◽  
Plateau Phase ◽  
Overall Response ◽  
Delayed Group

Background: High dose chemotherapy and autologous stem cell transplant (SCT) remains the preferred therapy for eligible patients with multiple myeloma (MM). Several studies have demonstrated an improvement in median survival with use of SCT. Patients with myeloma may undergo SCT immediately following 4–6 cycles of ‘induction’ therapy or at the time of relapse from the initial plateau phase. Available evidence does not suggest a survival difference between the two approaches. Methods: We retrospectively evaluated our experience with autologous single SCT for MM to compare the results of delayed SCT to early SCT. We identified from our transplant database, 202 patients with MM, who underwent SCT between October 1992 and November 2002. 101 patients, who responded to induction chemotherapy, had stem cells collected in plateau phase, received maintenance chemotherapy and had SCT at the time of first relapse (delayed SCT group). The remaining 101 patients, after initially achieving a response underwent upfront SCT (early SCT group). Patients refractory to initial therapy were excluded from this study. Most of the early transplants were done in the recent years and hence this group has a shorter follow up. Results: The study cohort had a median age of 55 years (range 29 – 72) at diagnosis consisting of 126 males (62%), with no significant demographic difference between the two groups. As expected measures of tumor burden (M protein, B2M and marrow plasma cell percentage) were significantly higher in the delayed group. Plasma cell labeling indices and presence of abnormal cytogenetics were higher in the delayed SCT group as well at transplant. TBI containing regimens were used more often in the delayed group reflecting a difference in the time periods of transplant. There was no difference between the groups in terms of overall response to transplant though complete response rate was higher for the early transplants. (Table). There was no difference in the time to overall response between the groups (P=0.13, Kaplan Meier estimate). Though the median progression free survival (PFS) from transplant was shorter for the delyaed SCT group, the overall survival (OS) from diagnosis of MM was comparable for the two groups (Table). The overall survival estimate at 5 year from diagnosis was 60% for both groups. Conclusions: Review of our experience demonstrates comparable overall survival for an early SCT compared to SCT at the time of relapse. Although there is an advantage for early SCT in terms of more chemosensitive disease as shown by a longer PFS from SCT, there is no benefit in OS from time of diagnosis. Patient preference and other co-morbidities should play a role in the decision regarding timing of transplant. This study has the disadvantage of being retrospective in nature and the two groups being spread over different periods in time. Early (n=101) Delayed (n=101) P Overall Response 100 (99%) 94 (94%) 0.07 Complete Response 43 (42%) 28 (27%) 0.04 Median PFS (From Transplant) 26.7 months 14.8 months <0.0001 Median OS (From diagnosis) 67 months 70 months 0.1

Delayed Platelet Engraftment and Outcome of Stem Cell Transplant for Multiple Myeloma: Possible Microenvironment Effect?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 939-939
Author(s):  
Shaji Kumar ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
Suzanne R. Hayman ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Complete Response ◽  
Cell Labeling ◽  
High Dose ◽  
Cell Transplant ◽  
Early Group ◽  
Time To Progression ◽  
Duration Of Response ◽  
Late Group

Background: Autologous stem cell transplantation is an effective treatment modality for patients with multiple myeloma. While most of the patients relapse after ASCT with a median time to progression of 2 years, there is a significant heterogeneity in the duration of response. It has been hypothesized that the effect of high dose alkylator therapy used for conditioning may have a dual effect on the myeloma cells as well as marrow microenvironment. It is also known that hematopoiesis, especially thrombopoiesis, depends to some extent on signals form the marrow microenvironment. We examined if there was any relationship between delayed platelet engraftment and outcome after ASCT. Methods: We examined the outcomes in a group of patients undergoing ASCT for myeloma at our institution to compare the response duration to platelet engraftment kinetics. We studied 687 patients undergoing ASCT with melphalan conditioning followed by peripheral blood stem cell transplant. Results: Among the 687 patients undergoing ASCT, 200 pts (29%) achieved a platelet count of 50,000 by day 21 (early group) and the rest achieved this level after 21 days or never engrafted (late group). The median time to progression (TTP) among the late group was 24.8 months (95% CI; 19.6, 30 months) vs. 16.8 months (95% CI; 15.1, 18.6 months) for the late group (p < 0.001) (Figure). Patients in the late engraftment group were more likely to achieve a complete response compared to the early group; 39% vs. 30%, p = 0.02. In a multivariate analysis examining factors predicting for longer time to progression after ASCT, delayed platelet engraftment was independent of transplant within 12 months of diagnosis, CR with ASCT, absence of cytogenetic abnormalities, B2M < 3.5 mg/L and a plasma cell labeling index < 1% at the time of ASCT (Table). Conclusions: In this study, we have demonstrated for the first time a relationship between delayed platelet engraftment after ASCT and the duration of response following ASCT. This intriguing finding raises several hypotheses. It is possible that the delayed platelet engraftment is a marker of marrow microenvironment dysfunction secondary to high dose therapy, given the role of marrow microenvironment on thrombopoiesis. It is possible that this is a surrogate marker for the biological effectiveness of the melphalan dose, which can affect the other cells in the marrow microenvironment as well. It is likely a reflection of the marrow microenvironment dependence on the myeloma cells for its survival. These findings should be confirmed in other larger patient groups. Predictors of progression Variable Hazard Ratio P Platelet Engraftment > 21 days 0.80 (0.60, 0.96) 0.02 Late transplant (>12 months from diagnosis) 1.6 (1.3, 2.0) <0.01 Plasma cell labeling index > 1% 1.9 (1.5, 2.4) <0.01 Complete response 0.41 (0.33, 0.51) <0.01 Abnormal Cytogenetics 1.8 (1.4, 2.3) <0.01 B2M > 3.5 1.2 (0.96, 1.5) 0.12 Figure Figure

scholarly journals Early Use of Dinutuximab Beta in Patients with High-Risk Neuroblastoma

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Neofit Spasov ◽  
Mariya Spasova
Keyword(s):  
High Risk ◽  
Induction Chemotherapy ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Post Induction ◽  
Early Use ◽  
Improve Patient

Neuroblastoma is the most common extracranial solid tumor in children, accounting for 15% of all pediatric cancer deaths. High-risk neuroblastoma (HRNB) is a particularly difficult-to-treat form of the disease that requires aggressive multimodality therapy, including induction chemotherapy, consolidation therapy with high-dose chemotherapy and autologous stem cell transplant, and maintenance therapy with dinutuximab beta. Despite treatment advances, the prognosis of these patients remains poor. As a better response to induction therapy has been associated with prolonged survival in patients with HRNB, we hypothesized that early use of dinutuximab beta—post-induction chemotherapy—may improve patient outcomes. We describe here our experience of administering at least one cycle of dinutuximab beta post-induction and prior to surgery in three children with HRNB who did not demonstrate a complete response to induction chemotherapy. All three patients achieved complete remission. Early use of dinutuximab beta may therefore have the potential to improve outcomes in patients with HRNB.

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