scholarly journals Maternal and Fetal Outcomes of Acute Leukemia in Pregnancy: A Retrospective Study of 52 Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Peng Wang ◽  
Zhen Yang ◽  
Meng Shan ◽  
Shenqi Lu ◽  
Luwei Zhang ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Induction Therapy ◽  
Low Dose ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
First Trimester ◽  
All Trans Retinoic Acid ◽  
The Status ◽  
Chemotherapy Patients ◽  
Low Dose Chemotherapy

Acute leukemia during pregnancy (P-AL) is a rare disease with limited data regarding the management and outcomes of mothers and fetuses. We retrospectively analyzed the characteristics, pregnancy outcomes and maternal and neonatal prognoses of 52 patients with P-AL collected from January 2013 to December 2020 in our center. Seventeen (32.7%) patients received chemotherapy during pregnancy (exposed cohort), while 35 (67.3%) received chemotherapy after abortion/delivery (nonexposed cohort). Twenty-six (50.0%) pregnancies ended with abortion, and 26 (50.0%) babies were born through spontaneous delivery or cesarean section. Seven infants (26.9%) were born in the exposed cohort, while 19 infants (73.1%) were born in the nonexposed cohort. Fetuses in the exposed cohort had lower gestational ages (P=0.030) and birth weights (P=0.049). Considering the safety of the fetus, seven patients in the exposed cohort received low-dose chemotherapy, one patient received all-trans retinoic acid (ATRA) and one patient only received corticosteroids as induction therapy. Patients received low-dose chemotherapy as induction therapy had a lower complete remission (CR) rate (P=0.041), and more patients in this group received HSCT (P=0.010) than patients received intensive chemotherapy. Patients who delayed chemotherapy in the nonexposed cohort experienced a trend toward a higher mortality rate than patients who received timely chemotherapy (P=0.191). The CR (P = 0.488), OS (P=0.655), and DFS (P=0.453) were similar between the exposed and nonexposed cohorts. Overall, the 4-year overall survival (OS) and disease-free survival (DFS) rates were estimated at 49.1% and 57.8%, respectively. All newborns were living, without deformities, or developmental and intellectual disabilities. Our study indicated that P-AL patients in the first trimester might tend to receive chemotherapy after abortion. Both the status of disease and patients’ willingness should be taken into consideration when clinicians were planning treatment strategies in the second or third trimester. Low-dose or delayed chemotherapy might decrease the efficacy of induction therapy and survival rate of patients, but HSCT could improve the prognosis.

Remission Induction Treatment for 6 Patients of Jehovah’s Witnesses with De Novo Acute Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4553-4553 ◽  
Author(s):  
Hiroyuki Fujita ◽  
Mai Iguchi ◽  
Takayoshi Tachibana ◽  
Sachiya Takemura ◽  
Jun Taguchi ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Retinoic Acid ◽  
Acute Leukemia ◽  
Induction Therapy ◽  
Low Dose ◽  
Remission Induction ◽  
Severe Thrombocytopenia ◽  
Severe Anemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract The treatment of acute leukemia with myelosuppressive chemotherapy usually requires the transfusions of blood and blood products. For religious reasons, Jehovah’s Witnesses (JW) do not consent to the transfusion of blood. We describe here six cases of JW with acute leukemia, who received induction chemotherapy without blood support. From January 1996 to March 2006, six JW with newly diagnosed acute leukemia received remission induction chemotherapy at Shizuoka Red Cross Hospital or Kanagawa Cancer Center (acute myeloid leukemia (AML) n=5, acute lymphoblastic leukemia (ALL) n=1). All patients refused the consent for transfusions of packed red cells and platelet units and they were never forced accept them. Remission induction therapy: One patient with M3 received all-trans retinoic acid alone. One ALL patient received prednisolone alone. Three AML patients received the following LVP regimen: L-asparaginase 5000U/sqm div from day 8 to day 21 + vincristine 1.4mg/sqm div day1, 6, 11, 16, 21, 26 + prednisolone 40mg/sqm div from day 1 to day 28, and one AML patient received a low dose of Ara-C regimen (20mg/sqm continuous div from day 1 to day 14). Results (see Table): Four out of six patients achieved complete remission and two paitents died from cardiac arrest due to severe anemia before hematological recovery. No patients developed fatal bleeding complications, not even long lasting severe thrombocytopenia. Conclusion: We have demonstrated the feasibility of remission induction therapy for JW with leukemia. This LVP regimen, or steroid based regimen, may be suitable for JW with acute leukemia because myelosuppression is relatively mild. While two patients experienced cardiac arrest due to severe anemia of under 3g/dL of hemoglobin, severe thrombocytopenia can be managed without prophylactic platelet transfusion. Clinical characteristics of patients Pt#:Age/Sex/FAB/ Karyotype Induction therapy Epo use Nadir in Induction therapy (day) Out come Follow-up from Induction therapy WBC(×109/L) Hb(g/dL) PLT(×109/L) ATRA: All-trans retinoic acid, PSL: Prednisolone, , LDAC: Low dose of Ara-C regimen, Epo: Erythropoietin, CR: Complete Remisson, ED: Early Death, RLPs: Relapse 1: 28/F/M3/t(15;17) ATRA Yes 0.9 (day2) 3.6 (day3) 20 (day2) CR 10Y6M+, 2ndCR 2: 29/F/M1/normal PSL+LVP No 0.6 (day4) 2.4 (day19) 16 (day6) CR 2Y6M, dead in 2nd RLPs 3: 45/F/M2/normal LVP No 0.9 (day22) 3.0 (day30) 8 (day25) CR 2Y1M+, in 1st CR 4: 25/M/M2/t(8;21) LVP Yes 1.2 (day25) 1.5 (day31) 17 (day31) ED 31days 5: 15/F/L1/complex PSL Yes 1.3 (day5) 3.8 (day7) 1 (day4) CR 10M+, in 1st CR 6: 64/M/M2/complex LDAC Yes 0.6 (day6) 2.7 (day21) 1 (day21) ED 23days

Leukemia during Pregnancy: 32 Cases from a Single Institution.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3153-3153
Author(s):  
Ayman Alhejazi ◽  
Mahmoud Aljurf ◽  
Entezam Sahovic ◽  
Fahed Almhareb ◽  
Irfan Maghfoor ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Gestational Age ◽  
Disease Free Survival ◽  
First Trimester ◽  
Underlying Disease ◽  
Salvage Chemotherapy ◽  
Cell Transplant ◽  
Single Institution ◽  
Live Births

Abstract In an attempt to evaluate the outcome of leukemia during pregnancy we performed a study of all such cases identified in our institution leukemia database. Thirty two cases were identified as cases of leukemia during pregnancy among the cohort of patients treated between January 1991 and July 2003. The cases were AML (15), ALL (6) and CML (11). At diagnosis the median age was 24.5 years and the median gestational age was 16 weeks. Twenty patients were treated for their leukemia during pregnancy at a median gestational age of 20 weeks (4 in the first trimester, 8 in the second trimester and 8 patients in the third trimester). Among the acute leukemia patients (n=21), 10 patients (47.6 %) received chemotherapy during pregnancy, 9 (90%) of them achieved CR and one patient needed salvage chemotherapy. Of these 10 patients, 7 had normal live births, one spontaneously aborted at 15 weeks of gestation and 2 had therapeutic abortion at 16 and 19 weeks of gestation. The remaining 11 (52.4%) were not given chemotherapy while pregnant as 3 patients (27.3%) presented late in their pregnancy after 34 weeks of gestation ending in normal live births and then received induction chemotherapy and 8 patients (72.7%) presented early in their pregnancy and they either spontaneously aborted or had a therapeutic termination of their pregnancy before starting chemotherapy. Among the CML patients (n=11), 9 patients received Hydroxyurea (HU) treatment during pregnancy, one patient received α-Interferon and one patient was treated with leukapheresis. Eight of the 11 patients (63.6%) had normal live births. Three patients (18.1%) aborted, 2 at 11 weeks of gestation while on HU treatment and one shortly after diagnosis before treatment. Of the total 32 patients 13 (40.6%) subsequently underwent allogeneic stem cell transplant, 8 for AML, 2 for ALL and 3 for CML. At a median follow up of 19.1 months, the disease free survival (DFS) and overall survival (OS) were 19% and 33.3% respectively for the acute leukemia patients. For CML patients, the OS was 90.9% at a median follow up of 38 months. The above data suggest that a high CR rate and satisfactory OS can be achieved in leukemia during pregnancy. Furthermore, chemotherapy did not lead to any teratogenic effects among live births. All spontaneous and therapeutic abortions were for disease related complications and not chemotherapy induced. This series of cases, which is the largest from a single institution, clearly supports early treatment of leukemia during pregnancy based on the underlying disease rather than concomitant pregnancy.

Clofarabine Plus Low-Dose Cytarabine Induction Followed by Consolidation with Clofarabine Plus Low-Dose Cytarabine Alternating with Decitabine as Frontline Therapy for Patients (pts) with Acute Myeloid Leukemia (AML) ≥ 60 Years (yrs).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2058-2058
Author(s):  
Sameer A Parikh ◽  
Hagop Kantarjian ◽  
Guillermo Garcia-Manero ◽  
Elias Jabbour ◽  
Tapan Kadia ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Research Funding ◽  
Low Dose ◽  
Single Agent ◽  
Disease Free Survival ◽  
Response Rates ◽  
High Response ◽  
Multiple Drugs ◽  
Low Dose Cytarabine

Abstract Abstract 2058 Poster Board II-35 Therapy of AML for elderly pts (≥ 60 yrs) remains challenging with low response rates, short durability of responses, and high toxicity rates following conventional therapy with standard-dose ara-C/anthracycline combinations. Clofarabine is a novel deoxyadenosine nucleoside analogue with single agent activity in frontline AML for older pts with ≥ 1 unfavorable prognostic factors. We have recently reported results of a randomized study suggesting higher response rates and comparable safety profile with the combination of clofarabine plus low-dose cytarabine over clofarabine alone. We have designed the current study of clofarabine plus low-dose cytarabine induction followed by consolidation with clofarabine plus low-dose cytarabine alternating with decitabine to maintain high response rates and improve disease-free survival based on the following hypotheses: 1) to extend duration of therapy by administering lower doses of the agents; and 2) to provide multiple drugs with different mechanisms of action to decrease risk of resistance. Pts were eligible if ≥ 60 yrs of age with newly diagnosed AML. Pts were excluded for ECOG PS > 2, creatinine > 1.5 mg/dL, cardiac ejection fraction < 40%, and prior therapy with clofarabine or decitabine. Induction therapy consisted of clofarabine 20mg/m2 i.v daily × 5 days plus cytarabine 20mg s.c. twice daily × 10 days in a laminar air flow room. Responding pts could receive up to 17 courses of consolidation therapy of clofarabine plus cytarabine (over 3 and 7 days, respectively) during consolidation courses 1-2, 6-8, 12-14) alternating with decitabine 20mg/m2 i.v. daily for 5 days during courses 3-5, 9-11, and 15-17. All pts received antibiotic prophylaxis with levofloxacin, valacyclovir and itraconazole (or equivalent). Forty pts have been enrolled with a median age of 70 yrs (range 60-80) of whom 22 (55%) had secondary AML (antecedent hematologic disorder in 11 pts). Two pts had received previous azacitidine for MDS. Fourteen pts (35%) had abnormal cytogenetics of whom 10 (25%) had monosomy 5, 7, or both. Four patients (10%) had a FLT3/ITD mutation. Of the 34 pts evaluable for response, 20 (59%) achieved CR and 2 (6%) CRp for an OR rate of 65%. Only 2 pts required 2 courses to CR. The OR rate for patients with diploid versus abnormal cytogenetics was 80% vs 50%; for pts with prior MDS versus no prior MDS 76% and 50%; and 75% for patients with FLT3 mutation. The median time to CR/CRp was 38 days (range 27-103). With a median follow up of 3.5 months (range 0.7-8.1), 2 pts relapsed (CR duration of 3.3 and 4.2 months, respectively); responses are ongoing in the remainder. Three pts (9%) died during induction therapy (one during re-induction) before a response could be established. The median number of consolidation cycles received by pts in CR was 3 (range 1-5). Most toxicities were ≤ grade 2 and included nausea/vomiting, diarrhea, rash, headache and mucositis. Six pts developed grade 3 elevations in serum transaminases which resolved at the end of induction therapy. Myelosuppression and neutropenic fever were common, but prolonged myelosuppression was rare. In conclusion, clofarabine plus low-dose cytarabine achieves high response rates with a manageable toxicity profile and low induction mortality in elderly pts with previously untreated AML. Time-to-event parameters will be provided with more extensive follow up. Disclosures: Off Label Use: Clofarabine and Decitabine in AML. Kantarjian:Genzyme: Consultancy, Research Funding. Faderl:Genzyme: Consultancy, Research Funding; Eisai: Research Funding, Speakers Bureau.

All-Trans Retinoic ACID and Low-Dose Chemotherapy For Acute Promyelocytic Leukaemia

2000 ◽  
Vol 109 (4) ◽  
pp. 896-897 ◽  
Author(s):  
Miguel A. Sanz ◽  
Jesús A. Martínez ◽  
Eva Barragán ◽  
Guillermo Martín ◽  
Francesco Lo Coco
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukaemia ◽  
Low Dose ◽  
Promyelocytic Leukaemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Low Dose Chemotherapy

scholarly journals Risk stratification–directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation

Blood ◽  
2012 ◽  
Vol 119 (14) ◽  
pp. 3256-3262 ◽  
Author(s):  
Chen-Hua Yan ◽  
Dai-Hong Liu ◽  
Kai-Yan Liu ◽  
Lan-Ping Xu ◽  
Yan-Rong Liu ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Acute Leukemia ◽  
Low Dose ◽  
Disease Free Survival ◽  
Donor Lymphocyte Infusion ◽  
Hematopoietic Stem ◽  
Group A ◽  
Group B ◽  
The Impact ◽  
Standard Risk

Abstract We studied the impact of risk stratification–directed interventions for minimal residual disease (MRD) on relapse and disease-free survival (DFS) prospectively in 814 subjects with standard-risk acute leukemia receiving allotransplantation in first or second complete remission. A total of 709 subjects were MRD− after transplantation (Group A); 105 subjects were MRD+, 49 received low-dose IL-2 (Group B), and 56 received modified donor lymphocyte infusion (DLI) with or without low-dose IL-2 (Group C). Posttransplantation immune suppression for GVHD was also modified based on MRD state. The cumulative risk of relapse was significantly less and DFS was significantly better in subjects in Group C than in subjects in Group B (P = .001 and P = .002, respectively), but was not different from subjects in Group A (P = .269 and P = .688, respectively). Multivariate analyses confirmed that MRD state and modified DLI were significantly correlated with relapse (P = .000, odds ratio [OR] = 0.255 and P = .000, OR = 0.269) and DFS (P = .001, OR = 0.511 and P = .006, OR = 0.436, respectively). These data suggest that risk stratification–directed interventions with modified DLI in patients with standard-risk acute leukemia who are MRD+ after transplantation may improve transplantation outcomes.

Risk-adapted treatment of acute promyelocytic leukemia with all-trans retinoic acid and anthracycline monochemotherapy: long-term outcome of the LPA 99 multicenter study by the PETHEMA Group

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3130-3134 ◽  
Author(s):  
Miguel A. Sanz ◽  
Pau Montesinos ◽  
Edo Vellenga ◽  
Consuelo Rayón ◽  
Javier de la Serna ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Low Dose Chemotherapy ◽  
High Degree

Abstract A previous report of the Programa de Estudio y Tratamiento de las Hemopatías Malignas (PETHEMA) Group showed that a risk-adapted strategy combining all-trans retinoic acid (ATRA) and anthracycline monochemotherapy for induction and consolidation in newly diagnosed acute promyelocytic leukemia results in an improved outcome. Here we analyze treatment outcome of an enlarged series of patients who have been followed up for a median of 65 months. From November 1999 through July 2005 (LPA99 trial), 560 patients received induction therapy with ATRA plus idarubicin. Patients achieving complete remission received 3 courses of consolidation followed by maintenance with ATRA and low-dose chemotherapy. The 5-year cumulative incidence of relapse and disease-free survival were 11% and 84%, respectively. These results compare favorably with those obtained in the previous LPA96 study (P = .019 and P = .04, respectively). This updated analysis confirms the high antileukemic efficacy, low toxicity, and high degree of compliance of a risk-adapted strategy combining ATRA and anthracycline monochemotherapy for consolidation therapy.

Adult Matched Sibling Blood Cell Transplants (BCT) after Myeloablative Conditioning Incorporating Daily Intravenous (IV) Busulfan (BU) and Low-Dose Antithymocyte Globulin (ATG): Outcomes with Particular Respect to Transplant-Related Mortality (TRM) in 140 Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2313-2313
Author(s):  
James A. Russell ◽  
Ahsan M. Chaudhy ◽  
Oluyeme Jeje ◽  
Diana Quinlan ◽  
Douglas Stewart ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Low Dose ◽  
Acute Gvhd ◽  
Myocardial Infarct ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Increase Risk ◽  
Cell Transplants ◽  
One Year ◽  
Related Mortality

Abstract Intravenous BU allows more predictable exposure and is more convenient to administer once daily than the conventional four times daily regimen. Low-dose pretransplant ATG may reduce morbidity and mortality from graft-versus-host disease (GVHD). We have investigated a myeloablative regimen incorporating these agents in 140 adults aged 18–65 (median 47) receiving a first MRD SCT between 05/99 and 01/04. Conditioning comprised fludarabine (FLU) 50mg/m2on days −6 to −2 and IV BU (Busulfex, ESP Pharma) 3.2 mg/kg daily days −5 to −2 inclusive (FLUBUP) in 116 patients (pts) with additional TBI 200cGy x 2 in 24 (14 ALL, 8AML, 2 biphenotypic). Forty-three pts had standard-risk (SR) acute leukemia in CR1 (35 AML, 8 ALL), and 23 had active acute leukemia (HA) (18 AML±MDS, 3 ALL, 2 biphenotypic). A third group of 74 other (OTH) pts comprised 2 AML CR2, 2 ALL CR2, 2 CML (1 AP, 1CP2), 13 MDS, 11 MM, 24 NHL, 6 HD (2 with CLL), 8 CLL, 5 other. All pts were given cyclosporine A, “short course” methotrexate with folinic acid and Thymoglobulin (Genzyme) (ATG) 4.5 mg/kg in divided doses over 3 consecutive days pretransplant finishing D0. Followup of survivors is 6–61 months, median 26. Incidence of acute GVHD (aGVHD) grade II–IV was 19±4%, grade III–IV 6±2% and chronic GVHD (cGVHD) 66±5% (at 2 years). Projected TRM is 4±2% at 100 days, 10±3% at 1 year and 14±4% at 5 years. For acute leukemia pts projected TRM at one year is 5±5% vs 12±5% with (n = 24) and without (n = 47) TBI respectively (p = ns). Four non-relapse deaths occurred before day 100 one each from myocardial infarct (MI), acute GVHD, candidiasis and VOD. Ten deaths between days 102–569 were related to aGVHD in one and complications in pts with cGVHD in 9 (occurring in 1 pt after 2nd BCT for graft failure) including 1 VZV, 3 other infection, 1 PE, 1 MI. Of 11 follicular NHL pts 3 died of cGVHD and its complications after 1st BCT compared with 5 of 129 others (p = 0.02). Twelve of the transplant-related deaths were in 76 pts ≥ 46 years old compared with 2 in 64 younger pts (TRM = 23±6%, vs 4±3%, p = 0.01). Of 55 relapsed pts 17 are alive, 8 of these are in remission after more treatment and/or onset of GVHD. Projected 5-year disease-free survival and survival respectively is 46±5% and 57±5% for all pts, 62±8% and 76±7% for SR, 51±7% and 59±9% for OTH, and 9±6% and 16±8% for HA. This study indicates that: 1) regimen related mortality is low in MRD BCT recipients given this regimen 2) cGVHD is the main cause of TRM 3) pts with follicular NHL seem to be comparatively susceptible to death related to cGVHD 4) addition of 400cGy TBI does not increase risk of TRM and 5) older age remains a risk factor for TRM.

scholarly journals Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low-dose chemotherapy, PMN/RAR-alpha isoform, and CD13 expression in patients treated with all-trans retinoic acid

Blood ◽  
1994 ◽  
Vol 84 (11) ◽  
pp. 3843-3849 ◽  
Author(s):  
L Vahdat ◽  
P Maslak ◽  
WH Jr Miller ◽  
A Eardley ◽  
G Heller ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Low Dose ◽  
Leukocyte Count ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Leukocyte Counts ◽  
Low Dose Chemotherapy ◽  
Retinoic Acid Syndrome

All-trans retinoic acid (RA) has proven a major advance in the treatment of acute promyelocytic leukemia (APL). However, the proper management of patients who present with or develop leukocytosis during remission induction with all-trans RA is not established, nor is there a clear relation between leukocytosis and the development of the retinoic acid syndrome. We reviewed the course of our patients who underwent induction with all-trans RA to identify potential factors that might predict for the development of this syndrome and to identify which patients, if any, might specifically benefit from additional treatment with cytotoxic chemotherapy. Seventy-eight courses of all- trans RA therapy were administered to patients with a molecular diagnosis of APL. Initial and peak leukocyte counts, their rate of rise, leukocyte count criteria developed in Europe, and cell surface marker expression were all analyzed relative to subsequent development of both the RA syndrome as well as all causes of early mortality. The outcome of patients who received specific treatment for retinoid- induced leukocytosis was also examined. No factor was found to consistently predict for the development of the RA syndrome. Although the occurrence of the syndrome was positively associated with the peak value of the peripheral blood leukocyte count (P = .001), neither the initial leukocyte count nor the rate of rise in leukocyte counts on days preceding onset of the syndrome were sufficiently well-correlated to be clinically useful (P = .21). The leukocyte count criteria developed in Europe had a sensitivity of 62%, a specificity of 69%, and a positive predictive value that ranged from only 44% to 72%. However, we unexpectedly found that basal expression of CD13 (aminopeptidase N), a cell surface enzyme previously linked to tumor cell invasion and an inferior outcome in patients with acute myeloid leukemia, was highly associated with both development of the syndrome (P < .05) as well as an elevated leukocyte count (P = .006). Neither low-dose chemotherapy nor leukapheresis prevented development of the syndrome nor ameliorated its effects. In fact, 9 of 11 patients who received these interventions sustained fatal or near-fatal events, most of which were due to hemorrhage. However, early treatment with a short-course of high-dose corticosteroids halted progression of the syndrome in most cases. Finally, we found that expression of the type “A” isoform of PML/RAR- alpha (also known as bcr3 or “short”) was associated with a significantly shorter duration of relapse-free and overall survival (P = .005).(ABSTRACT TRUNCATED AT 400 WORDS)

Combination Imatinib with Interferon-α For Philadelphia Positive Acute Lymphocytic Leukemia: A Mutiple Centers Study In China

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5019-5019
Author(s):  
Pu Kuang ◽  
Yu Wu ◽  
Bing Xiang ◽  
Hongbing Ma ◽  
Hong Chang ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Induction Therapy ◽  
Acute Lymphocytic Leukemia ◽  
Low Dose ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Maintenance Chemotherapy ◽  
Intensified Chemotherapy ◽  
Low Dose Chemotherapy ◽  
Disease Free

Abstract Background Imatinib combined with chemotherapy for induction and intensification therapy has become the standard strategy for Philadelphia-positive acute lymphocytic leukemia (Ph+ALL). Anyhow, intensified chemotherapy lead to about 5% of early death. Because we believed that imatinib plays the most important role in Ph+ALL treatment, we started Ph+ALL-HX-200803 trial (WHO ICTRP Registry No. ChiCTR-TNRC-00000309 ) to test the effect of combining imatinib and low dose chemotherapy and added interferon-¦Á in maintenance to prevent relapse. Method According to our protocol, all patients received imatinib 400mg daily, vindesine 4 mg weekly and dexamethasone 10mg/m2/day for 4 days per week for 4 weeks as induction therapy. For patients under 55 years old, we give them three sequential courses of intensified chemotherapy (CAM, high dose MTX+L-Asp, and MA, CALLG2008 protocol). Patients in CR1 would receive allogenic HSCT if they had suitable donors. Those who were reluctant to receive or unsuitable for allo-HSCT received maintenance therapy with imatinib 400mg daily, interferon-¦Á 3 million unit 2-3 doses per week and chemotherapy. Maintenance chemotherapy including vindesine and dexamethasone was given monthly in the first year, once every two months in the second year, and once every three months in the third year. For patients over 55 years old, we skipped intensified chemotherapy and gave them maintenance therapy directly. Minimal residual disease surveillance was conducted by BCR/ABL fusion gene quantification. The main endpoints were 3-year overall survival and disease free survival. Result Between 2008 and 2012, 50 patients with newly diagnosed Ph+ALL were enrolled. The median age of this group of patients was 35.5 years old. All but one patients achieved complete remission (98%) after 4 weeks induction therapy. No patient died during induction therapy. The median follow-up time was 27 months. The estimated 3-year DFS and OS were 38.8 ±9.2% and 52.7±10.4%. Five patients received allo-HSCT in CR1. For patients who did not receive allo-HSCT in CR1, 1 patient survived for more than 5 years, 7 patients survived for more than 3 years. In post-hoc analysis, patients achieved MRD negativity at six month showed better median DFS (not reached vs. 11 moths, p=0.001) and OS (not reached vs. 22 months, p=0.015) compared to those who did not. Conclusion The outcomes of our study suggest that imatinib combing with low dose chemotherapy showed a high and safe induction remission rate, combination of interferon-¦Á with imatinib and maintenance chemotherapy might improve the outcomes of patients with Ph+All who were not eligible for Allo-HSCT. MRD status at six month is an important prognostic indicator. The long term disease-free survivors may signal the possibility of a cure even without allo-HSCT. Disclosures: No relevant conflicts of interest to declare.

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