Venothromboembolism (VTE) in Patients (pts) with Acute Lymphocytic Leukemia (ALL), Burkitt’s Leukemia/Lymphoma (BL) or Lymphoblastic Lymphoma (LL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4338-4338
Author(s):  
Khanh D. Vu ◽  
Julie C. Hubbard ◽  
E. Lin ◽  
Stefan H. Faderl ◽  
Jorge E. Cortes ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Hematological Malignancies ◽  
Philadelphia Chromosome ◽  
Significant Proportion ◽  
Lymphocytic Leukemia ◽  
Cancer Center ◽  
High Dose ◽  
Cell Transplant ◽  
Acute Leukemias ◽  
History Of

Abstract It has been reported that cancer increases the risk of VTE 4-6-fold. The incidence of VTE in cancer pts has been estimated at 1 in 200 per year and has been well documented in solid tumors. Far less is known about the incidence of VTE in pts with hematological malignancies although a recent publication (Blom et al, JAMA293:715, 2005) suggested that pts with hematological malignancies such as lymphoma and multiple myeloma may be at a higher risk of developing VTE than pts with solid tumors. The incidence and risk of VTE has not been well studied in acute leukemias, a population in which prophylaxis is underutilized given the thrombocytopenia associated with intensive chemotherapy. To evaluate the incidence of VTE in pts with hematological malignancies further and to assess the need for VTE prophylaxis, we conducted a retrospective chart review of 299 pts with ALL, BL, or LL who were seen at M.D. Anderson Cancer Center Center from November 1999 to May 2005. Pts received a hyper-CVAD based regimen (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and high-dose cytarabine). The median observation period was 188 weeks (range 1–328 wks) and included post-consolidation chemotherapy, allogeneic stem cell transplant, and/or salvage chemotherapy. Among 298 evaluable pts, 52 (17%) had confirmed VTE by imaging studies. In 7 pts, VTE was the presenting sign of the malignancy. The median age of pts who developed VTE was significantly higher than of those who did not develop VTE, 48.5 yrs (range 19–75) vs. 42 yrs (range 15–83), respectively (p=0.04). With each year increase in age, the risk of having VTE increased approximately by 1.7% (p=0.059). ALL pts with Philadelphia chromosome (Ph) had a higher incidence of VTE than all other pts (p=0.02), and were 1.8 times more likely to have VTE than non-Ph ALL pts (p=0.007). Caucasian pts or those with history of prior VTE had a significantly higher incidence of VTE (p=0.03 and p=0.002, respectively). The risk was 2 fold higher for Caucasians and 12 fold higher for those with a prior history of VTE. At the time of VTE, platelet counts were below 50 x 109/L in 33%, 50–100 x 109/L in 10%, and greater than 100 x 109/L in 57%. VTE occurs in a significant proportion of pts with ALL, BL, and LL. Thrombocytopenia does not preclude the development of VTE. Older age, Ph positivity, race, and history of prior VTE were significantly associated with the development of VTE. Further analysis of other known risk factors such as the use of erythropoiesis-stimulating agents, hormonal therapy, and other comorbidities is underway to better refine the subpopulation at risk.

Occurence of venothromboembolism (VTE) in patients (pts) with acute lymphocytic leukemia (ALL), Burkitt's leukemia/lymphoma (BL), or lymphoblastic leukemia (LL)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7059-7059
Author(s):  
N. V. Luong ◽  
H. M. Kantarjian ◽  
S. H. Faderl ◽  
D. A. Thomas ◽  
K. D. Vu
Keyword(s):  
Risk Factors ◽  
Lymphoblastic Leukemia ◽  
Hormone Replacement ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Pulmonary Vasculature ◽  
Cancer Center ◽  
Public Health Issue ◽  
Female Ratio ◽  
History Of

7059 Background: Venous thromboembolism (VTE) is a significant public health issue. Although neoplastic diseases are known risk factors for the development of VTE, little is known about the incidence and predisposing factors of VTE among leukemia patients (pts). Methods: We performed a retrospective study to determine the incidence and risk factors associated with development of VTE among pts with ALL, BL, LL at M. D. Anderson Cancer Center between 1999 and 2005. Medical records of 299 ALL pts were reviewed and analyzed. All computations were conducted using Stata 10. Results: Of the 299 pts with a male/female ratio of 182/117 and a median age of 43 yrs (range 15–83 yrs), 18% had VTE. Recurrent VTE occurred in 10 pts. VTE were identified in upper extremities (59%), lower extremities (30%), pulmonary vasculature (7%), and within venous catheters (4%). In a univariate model, pts with baseline platelet (plt) count 50–99 x 109/L were 2.2 times (95% CI: 1.05–4.55) more likely to develop VTE than pts who had plt >100 x 109/L. Pts aged 40–59 yrs were 2.3 times (95% CI: 1.15–4.59) more likely to develop VTE than pts aged 15–39 yrs. Women were 1.8 times (95%CI: 1.04–3.4) more likely than men to have a VTE. Pts with a history of VTE were 15.2 times (95% CI: 2.97–77.51) more likely to develop a VTE than pts who had no prior VTE history. Pts with > 3 comorbidities were 2.6 times (95% CI: 1.19–5.48) more likely to develop VTE than pts without comorbidities. Pts who used oral contraception or hormone replacement therapy (OCP/HRT) were 2 times (95% CI: 1.07–3.92) more likely to develop VTE than non-users. Pts with Philadelphia chromosome (Ph)-positive ALL were 3 times (95%CI: 1.41–6.17) more likely to develop VTE than pts with Ph-negative ALL. In a multivariate model, significant predictors of VTE were age 40–59 yrs, plt count 50–99 x 109/L, diagnosis of Ph-positive ALL, history of VTE, and OCP/HRT use. Conclusions: Pts with ALL have a high VTE rate. In addition to traditional risk factors, disease-specific features may also predispose pts to higher VTE risk. Further studies should be done in other leukemias to establish guidelines in the prevention and management of VTE in pts with leukemia. [Table: see text]

Improving the care of acute lymphocytic leukemia (ALL) at a large county hospital.

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 213-213 ◽  
Author(s):  
Meghan Sri Karuturi ◽  
Jeffrey Thomas Yorio ◽  
Annie Titus ◽  
Stephenie Jeanette Pharr ◽  
Alyssa G. Rieber
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Underserved Populations ◽  
Philadelphia Chromosome ◽  
The United States ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed

213 Background: The treatment of ALL involves complex chemotherapy regimens that are difficult to deliver to underserved populations. Lyndon B. Johnson General Hospital (LBJGH) provides care to uninsured and underinsured patients in Harris County, the third largest county in the United States. Our goal is to achieve 80% adherence to National Comprehensive Cancer Network guidelines in the care of newly diagnosed ALL patients at LBJGH. Methods: The charts of 14 patients with newly diagnosed ALL were reviewed. Demographics, initial work-up (e.g., bone marrow biopsy and aspirate), type of treatment, adherence to scheduled treatment, use of supportive medications, outpatient follow-up, stem cell transplant referral and quality of provider documentation were collected. Areas of potential improvement were then identified using provider focus groups and Ishikowa Diagram. The project was approved by the MD Anderson Quality Improvement Assessment Board. Results: 12/14 patients were evaluable, having received their full course of care at LBJGH. The median age was 35, 9/12 (75%) were female and 9/12 (75%) were Hispanic. 6/11 (55%) cases expressed CD20 (CD20+) and 3/11 (27%) were Philadelphia chromosome positive (Ph+). All 12 patients received induction and consolidation therapy with the HyperCVAD regimen (cyclophosphamide/vincristine/doxorubicin/dexamethasone alternating with high-dose methotrexate/cytarabine). Bone marrow biopsy at time of diagnosis, use of a tyrosine kinase inhibitor for Ph+ ALL, and use of supportive medications occurred >80% of the time. Administration of outpatient chemotherapy, use of rituximab for CD20+ ALL, outpatient lab follow-up, intrathecal chemotherapy and appropriate referral for allogeneic transplant occurred 50-80% of the time. Provider documentation was appropriate <50% of the time. Conclusions: Based on these findings, we established a standard algorithm of care for ALL patients at LBJGH, enhanced provider education through the design and distribution of teaching tools, created a checklist to facilitate handoffs between providers and established expectations for documentation. In the future, we would also like to add a patient navigator to further improve coordination of care.

scholarly journals Autoimmune Complications in Hematologic Neoplasms

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1532
Author(s):  
Wilma Barcellini ◽  
Juri Alessandro Giannotta ◽  
Bruno Fattizzo
Keyword(s):  
Lupus Erythematosus ◽  
Checkpoint Inhibitors ◽  
Myeloproliferative Neoplasms ◽  
Pure Red Cell Aplasia ◽  
Lymphocytic Leukemia ◽  
Cell Transplant ◽  
Acute Leukemias ◽  
Hematopoietic Stem ◽  
Non Hodgkin Lymphoma ◽  
Diagnostic Difficulties

Autoimmune cytopenias (AICy) and autoimmune diseases (AID) can complicate both lymphoid and myeloid neoplasms, and often represent a diagnostic and therapeutic challenge. While autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) are well known, other rarer AICy (autoimmune neutropenia, aplastic anemia, and pure red cell aplasia) and AID (systemic lupus erythematosus, rheumatoid arthritis, vasculitis, thyroiditis, and others) are poorly recognized. This review analyses the available literature of the last 30 years regarding the occurrence of AICy/AID in different onco-hematologic conditions. The latter include chronic lymphocytic leukemia (CLL), lymphomas, multiple myeloma, myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), myeloproliferative neoplasms, and acute leukemias. On the whole, AICy are observed in up to 10% of CLL and with higher frequencies in certain subtypes of non-Hodgkin lymphoma, whilst they occur in less than 1% of low-risk MDS and CMML. AID are described in up to 30% of myeloid and lymphoid patients, including immune-mediated hemostatic disorders (acquired hemophilia, thrombotic thrombocytopenic purpura, and anti-phospholipid syndrome) that may be severe and fatal. Additionally, AICy/AID are found in about 10% of patients receiving hematopoietic stem cell transplant or treatment with new checkpoint inhibitors. Besides the diagnostic difficulties, these AICy/AID may complicate the clinical management of already immunocompromised patients.

scholarly journals 1098. Norovirus Infection in Cancer Patients Undergoing Chimeric Antigen Receptor T-cell Immunotherapy (CAR-T)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S578-S579
Author(s):  
Divya S Kondapi ◽  
Sasirekha Ramani ◽  
Adilene Olvera ◽  
Robert L Atmar ◽  
Mary K Estes ◽  
...  
Keyword(s):  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Nucleic Acid Amplification ◽  
High Dose ◽  
Cell Transplant ◽  
Research Support ◽  
Hematopoietic Stem ◽  
Car T Cell ◽  
Car T

Abstract Background CAR-T is used to treat certain refractory hematological malignancies. B-cell aplasia and immunosuppression used to treat CAR-T side effects increase infection risk. Little data are available describing Norovirus (NoV) infections in CAR-T recipients. Methods We reviewed the medical records of 134 patients with NoV diarrhea (identified by nucleic acid amplification test) between 2016-2019. Of these patients, nine received CAR-T prior to developing NoV. Here we describe their demographics, clinical characteristics, treatments, and complications. Results The median age was 49 years (Table 1). Patients’ underlying malignancies included Non-Hodgkin’s Lymphoma (4), Acute Lymphoblastic Leukemia (3), Chronic Lymphocytic Leukemia (1) and metastatic Sarcoma (1). Prior to development of NoV, six patients had undergone hematopoietic stem cell transplant, and 1 had received checkpoint inhibitor therapy. Five patients experienced cytokine release syndrome after CAR-T, and 1 experienced CAR-T-related encephalopathy syndrome (Table 2). Two patients received interleukin-6 antagonist therapy, and one received high dose steroids. Time to diarrhea onset post-CAR-T cell infusion was variable(median 256days, IQR 26-523 days).Six had an absolute lymphocyte count&lt; 1000/mm3 at diarrhea onset. Three had diarrhea for &gt;14 days; median diarrhea duration in the other 6 patients was 4 days. Other GI complaints included abdominal pain (3), nausea (4), and vomiting (3). For NoV treatment, three received oral immunoglobulin, and 8 received Nitazoxanide. Complications included development of concomitant GI-GVHD(5), ileus (2), need for TPN (3), renal failure requiring dialysis (2), ICU stay (3), and death (2). Two patients were co-infected with other enteropathogens such as rotavirus, enteropathogenic and enteroaggregative E.Coli and Clostridioides difficile. Three patients with diarrhea lasting &gt;14 days had serial samples collected over time; NoV shedding lasted 81-546 days. NoV was genotyped in 6 patients(Table 3) and included GII.2(2), GII.4(2), GII.6(1) and GII.12(1). Table 1: Patient characteristics (N=9) Table 2: CAR-T related factors Table 3: NoV Genotypes Conclusion NoV belonging to various genotypes is an important cause of acute and chronic diarrhea in patients receiving CAR-T cell therapy. Disclosures Adilene Olvera, MPH MLS (ASCP), MERK (Grant/Research Support, Scientific Research Study Investigator) Robert L. Atmar, MD, Takeda Vaccines, Inc. (Grant/Research Support) Mary K. Estes, PhD, Takeda Vaccines (Consultant, Grant/Research Support)

Results of Treatment With Hyper-CVAD, a Dose-Intensive Regimen, in Adult Acute Lymphocytic Leukemia

2000 ◽  
Vol 18 (3) ◽  
pp. 547-547 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Susan O’Brien ◽  
Terry L. Smith ◽  
Jorge Cortes ◽  
Francis J. Giles ◽  
...  
Keyword(s):  
B Cell ◽  
Acute Lymphocytic Leukemia ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Prognostic Models ◽  
Poor Performance Status ◽  
High Dose ◽  
Cell Disease ◽  
Adult Acute Lymphocytic Leukemia ◽  
Intensive Regimen

PURPOSE: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37% were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%. Leukocytosis of more than 30 × 109/L was found in 26%, Philadelphia chromosome–positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). RESULTS: Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91% v 75%, P < .01) and CR rate after one course (74% v 55%, P < .01) and better survival (P < .01), and a smaller percentage had more than 5% day 14 blasts (34% v 48%, P = .01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy. CONCLUSION: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.

Primary and Secondary Central Nervous System Lymphoma: Outcomes from Houston Methodist Cancer Center

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Cesar Gentille Sanchez ◽  
Ethan Burns ◽  
Ibrahim Muhsen ◽  
Humaira Sarfraz ◽  
Carlo Guerrero ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Cancer Center ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Female Ratio ◽  
Multiagent Chemotherapy

Introduction Primary Central Nervous System Lymphoma (PCNSL) is a rare form of extra-nodal non-Hodgkin Lymphoma (NHL), with diffuse large B-cell Lymphoma (DLBCL) reported in 90% of cases. Secondary CNS lymphoma (SCNSL) may occur as an isolated recurrence of previously diagnosed NHL or occur simultaneously as a manifestation of systemic disease. Comparative data on survival in treated PCNSL and SCNSL in the real-world setting is lacking. We present a retrospective analysis of outcomes in PCNSL and SCNSL patients treated at the Houston Methodist Cancer Center. Methods We retrospectively identified patients with a diagnosis of PCNSL or SCNSL from 2015 to 2020. Data collected included age, race, sex, diagnosis (PCNSL, SCNSL), histology and immunohistochemistry, treatment type (chemotherapy, radiation), transplant rates as well as outcomes (alive/dead). Responses were classified as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Survival was analyzed using Kaplan-Meier methodology, and log-rank tests were used to compare survival distributions. P &lt; 0.05 was considered statistically significant. Results There were 50 patients with CNS lymphoma identified between 2015 and 2020; 68% were PCNSL. Out of 43 with available pathology, 2 patients were T-cell lymphomas and 41 DLBCL. Out of the DLBCL cases, 95% of cases expressed CD20 while close to 60% were positive for MUM1, bcl-2 and bcl-6. Less than 15% of cases were positive for CD10. CD30 was positive in 17% of cases. Cerebral hemispheres (76%) was the most common organ involved, followed by ocular (8%), intraventricular space (6%) and cerebellum (6%). Median age at diagnosis was 67 years; male to female ratio was 1.27. Caucasian (62%) and Hispanic (24%) were most common ethnicities. Epstein-Barr Virus was positive in 14% of patients (5 in PCNSL and 2 in SCNSL). One patient with SCNSL had human immunodeficiency virus. The median follow-up time was 9.1 months. Multiagent chemotherapy including high dose methotrexate (MTX), cytarabine and rituximab was given to 48% of the patients while 32% received high dose MTX alone plus rituximab. From the latter group, five out of sixteen patients received temozolomide. Other regimens were used in 6% of the cases. Median dose of MTX in a multiagent chemotherapy regimen was 2.5gr/m2 and 2.25gr/m2 when used alone or with temozolomide. Median number of cycles given was 3. Radiation therapy alone was given to 8% of cases. Three patients did not receive treatment. For patients with PCNSL, overall response rate (ORR) was 82.8% (CR 65.5%, PR 13.8%, SD 3.4%). ORRs were similar between multiagent chemotherapy and methotrexate alone (+/- temozolomide) with 86.7% and 83.3% respectively. ORR for SCNSL was 57.1% (CR 35.7%, PR 21.4%); only 1 patient was treated with MTX alone. Further lines of therapy were required in 9.3% of patients. Consolidation with whole brain radiation was given in 22% of the cases (29.4% for PCNSL and 6.3% for SCNSL). Autologous stem cell transplant was performed in 10% of the patients (2 PCNSL, 3 SCNSL). Overall survival for patients with PCNSL was 74.8 months and 10.1 months for SCNSL (p=0.0444) (Figure 1). Survival was not significant between patients receiving multiagent chemotherapy and MTX alone or in combination with temozolomide (3-year OS 57.3% vs 73.4%, p= 0.5652) (Figure 2). Conclusion Most patients diagnosed with PCNSL are non-germinal center DLBCL. Median MTX dose was lower than 3gr/m2 with excellent ORR of over 80% in PCNSL. Response rates were lower in SCNSL and in general, patients with PCNSL had better outcomes. Survival did not differ significantly between regimens, suggesting that a lower intensity therapy may perform similarly to multiagent chemotherapy. These results need to be confirmed by prospective studies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Trends in the risk of second primary malignancies among survivors of chronic lymphocytic leukemia

2019 ◽  
Vol 9 (10) ◽  
Author(s):  
Vivek Kumar ◽  
Sikander Ailawadhi ◽  
Leyla Bojanini ◽  
Aditya Mehta ◽  
Suman Biswas ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hematological Malignancies ◽  
Lymphocytic Leukemia ◽  
Second Primary ◽  
Standardized Incidence Ratio ◽  
Improved Outcomes ◽  
History Of ◽  
Second Primary Malignancies

Abstract With improving survivorship in chronic lymphocytic leukemia (CLL), the risk of second primary malignancies (SPMs) has not been systematically addressed. Differences in risk for SPMs among CLL survivors from the Surveillance, Epidemiology, and End Results (SEER) database (1973–2015) were compared to risk of individual malignancies expected in the general population. In ~270,000 person-year follow-up, 6487 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI:1.17–1.23). The higher risk was for both solid (SIR 1.15; 95% CI:1.12–1.18) and hematological malignancies (SIR 1.61; 95% CI:1.5–1.73). The highest risk for SPMs was noted between 2 and 5 months after CLL diagnosis (SIR 1.57; 95% CI:1.41–1.74) and for CLL patients between 50- and 79-years-old. There was a significant increase in SPMs in years 2003–2015 (SIR 1.36; 95% CI:1.3–1.42) as compared to 1973–1982 (SIR 1.19; 95% CI:1.12–1.26). The risk of SPMs was higher in CLL patients who had received prior chemotherapy (SIR 1.38 95% CI:1.31–1.44) as compared to those untreated/treatment status unknown (SIR 1.16, 95% CI:1.13–1.19, p < 0.001). In a multivariate analysis, the hazard of developing SPMs was higher among men, post-chemotherapy, recent years of diagnosis, advanced age, and non-Whites. Active survivorship plans and long-term surveillance for SPMs is crucial for improved outcomes of patients with a history of CLL.

Pulmonary Mortality after High-Dose Oral Busulfan and Autologous Stem Cell Transplant (ASCT) in Patients with Non-Hodgkin Lymphoma (NHL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1764-1764
Author(s):  
Matt Kalaycio ◽  
Brad Pohlman ◽  
Lisa Rybicki ◽  
Ronald Sobecks ◽  
Elizabeth Kuczkowski ◽  
...  
Keyword(s):  
Pulmonary Toxicity ◽  
Pulmonary Function Tests ◽  
Multivariable Analysis ◽  
Pulmonary Complications ◽  
High Dose ◽  
Cell Transplant ◽  
Lower Baseline ◽  
Increased Risk ◽  
Dose Oral ◽  
History Of

Abstract Many high-dose chemotherapy preparative regimens include agents known to cause pulmonary toxicity such as BCNU. Chemotherapy induced pulmonary toxicity may be fatal. From 1/1/93 to 12/31/04 we treated 533 NHL patients with oral busulfan 14mg/kg, VP-16 60 mg/kg, and cyclophosphamide 120 mg/kg followed by ASCT. Busulfan levels were not measured. We have followed these patients for toxicity, survival, and cause of death (COD). Of these 533 patients, 214 have died, and 53 have died without relapse (15%). Most patients (n=329; 62%) had intermediate grade NHL by the IWF system. The median age was 50 years (range, 16–77) and 43% had a history of smoking. Radiotherapy was delivered to 27% and less than 3 chemotherapy regimens were administered to 75% of patients before ASCT. Sixteen patients (3%) died of non-relapse pulmonary complications. The median time to pulmonary mortality was 5 months (range, 2.5 – 21.4 months). We routinely screen patients with pulmonary function tests including DLCO before ASCT and most patients (n=490; 92%) were screened at a median of 45 days after ASCT (range, 7–90 days). For patients for whom data was available, there was no significant decrease in the median pre-ASCT and the post-ASCT DLCO in the either the whole cohort of patients or the patients dying of pulmonary complications. However, a lower baseline DLCO before ASCT predicted for pulmonary mortality after ASCT in univariable and multivariable analysis. Patients with a baseline DLCO &lt;94% predicted, had an increased risk of pulmonary mortality compared to patients with a baseline DLCO ≥94% predicted (p=0.016). Other significant risk factors included older age, lower baseline FEV1, prior radiotherapy, and longer time from diagnosis to ASCT. A history of smoking and disease status at the time of ASCT did not predict for pulmonary mortality. Because patients died of pulmonary complications at other institutions, we could neither determine treatment, nor confirm chemotherapy induced pulmonary toxicity. However, the early onset of pulmonary mortality after ASCT suggests the possibility of a toxic insult. Busulfan is a known pulmonary toxin, but the dose in this series of patients is relatively low and we have not seen similar pulmonary complications in 95 patients (median age 52 years) with myeloma treated with the combination of busulfan 16 mg/kg and cyclophosphamide 120mg/kg. Nonetheless, caution is warranted for older patients being treated with high-dose oral busulfan.

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

Phase II Study of Combination of the HyperCVAD Regimen with Dasatinib in Patients with Philadelphia Chromosome (Ph) or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL) and Lymphoid Blast Phase Chronic Myeloid Leukemia (CML-LB).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2814-2814 ◽  
Author(s):  
Farhad Ravandi ◽  
Deborah Thomas ◽  
Hagop Kantarjian ◽  
Stefan Faderl ◽  
Charles Koller ◽  
...  
Keyword(s):  
Phase Ii ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Clinical Activity ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Blast Phase ◽  
Platelet Recovery

Abstract Combination of cytotoxic chemotherapy with imatinib has improved the outcome for patients with Ph+ ALL and resulted in eradication of minimal residual disease and durable remissions without allogeneic stem cell transplant in some patients (Thomas D, Blood, 2004; Yanada M, JCO, 2006; Wassmann B, Blood, 2006; de Labarthe A, Blood, 2007). The dual Src and Abl inhibitor dasatinib has a significantly higher in vitro kinase inhibition against BCR-ABL and has demonstrated potent clinical activity in patients with imatinib-resistant lymphoid blast phase CML (CML-LB) and Ph+ ALL with over 50% complete cytogenetic responses (CG CR) in phase I and II trials but with median progression free survival of only 3 to 4 months. We are conducting a phase II trial in which patients with newly diagnosed or relapsed Ph+ ALL or CML-LB receive dasatinib 50 mg po bid for the first 14 days of each of 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate. Patients in complete remission (CR) continue to receive maintenance dasatinib 50 mg po bid daily and vincristine and prednisone monthly for 2 years followed by dasatinib indefinitely. To date 15 newly diagnosed patients with Ph+ ALL (cohort I) and 4 patients with relapsed Ph+ ALL or CML-LB (cohort II) have received a median of 4 cycles (range 1 – 8); 4 patients are receiving maintenance in CR. Median age for cohort I is 55 years (range 23 – 79) and for cohort II, 43 years (range 26 – 69); 13 and 3 patients were older than 50 years, respectively. Median WBC at diagnosis for cohort I was 4.3 × 109/L (range, 0.8 – 203.4 x 109/L). Three patients had CNS involvement. Fourteen and 3 patients in the 2 cohorts are evaluable for response to induction; 2 are too early. Thirteen patients (93%) in cohort I and all evaluable patients in cohort II have achieved CR after the first cycle; 1 patient in cohort I died on day 20 from infections before response assessment; her bone marrow exam on day 14 showed no detectable disease. Ten of 11 (91%) patients in cohort I have achieved CG CR after 1 cycle; 3 are too early. Three of 4 patients in cohort II have achieved CG CR after 1 cycle; 1 had a new CG abnormality and 1 is too early. Six patients have achieved complete molecular remission after the first cycle with the lowest BCR-ABL/ABL in the other patients ranging from 0.01 to 1.91. Median time to neutrophil and platelet recovery for cohort I is 18 and 25 days and for cohort II 18.5 and 30.5 days. Grade 3 and 4 toxicity has included 7 episodes of GI bleeding as well as infections, diarrhea, hypophosphatemia, hypocalcemia, elevated transaminases, and acute renal failure unrelated to treatment. With a median follow up of 4 months (range, 0 – 10), 15 patients are alive and in CR; 1 died at induction, 1 died in CR from an unrelated cardiac event, and 2 are too early. No patient has relapsed and no patient has received an allogeneic transplant. We conclude that the combination of the hyperCVAD regimen with dasatinib is feasible and can achieve early molecular remissions in patients with Ph+ ALL and CML-LB.

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