Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial.

Fifty-four percent of adults with acute lymphoblastic leukemia (ALL) who entered the LALA-94 trial experienced a first relapse. We examined the outcome of these 421 adult patients. One hundred and eighty-seven patients (44%) achieved a second complete remission (CR). The median disease-free survival (DFS) was 5.2 months with a 5-year DFS at 12%. Factors predicting a better outcome after relapse were any transplant performed in second CR (P<0.0001), a first CR duration >1 year (P=0.04) and platelet level >100 x 10(9)/l at relapse (P=0.04). Risk groups defined at diagnosis and treatment received in first CR did not influence the outcome after relapse. The best results were obtained in a subset of patients who were eligible for allogeneic stem cell transplantation (SCT). Geno-identical allogeneic SCT was performed in 55 patients, and 3 patients received donor lymphocyte infusions. Forty-four transplantations were performed from an unrelated donor (of which four were cord blood). We conclude that most adult patients with recurring ALL could not be rescued using current available therapies, although allogeneic SCT remains the best therapeutic option.     

Outcome of treatment after first relapse in younger adults with acute myeloid leukemia initially treated by the ALFA-9802 trial

Forty-seven percent of adults with acute myeloid leukemia (AML) who entered the ALFA-9802 trial and achieved a first complete remission (CR) experienced a first relapse. We examined the outcome of these 190 adult patients. Eighty-four patients (44%) achieved a second CR. The median overall survival (OS) after relapse was 8.9 months with a 2-year OS at 25%. Factors predicting a better outcome after relapse were stem cell transplant (SCT) performed in second CR and a first CR duration >1 year. Risk groups defined at the time of diagnosis and treatment received in first CR also influenced the outcome after relapse. The best results were obtained in patients with core binding factor (CBF)-AML, while patients initially defined as favorable intermediate risk showed a similar outcome after relapse than those initially entering the poor risk group. We conclude that most adult patients with recurring AML could not be rescued using current available therapies, although allogeneic SCT remains the best therapeutic option at this stage of the disease.     

Long-term follow-up of patients with newly diagnosed adult acute lymphoblastic leukemia: a single institution experience of 378 consecutive patients over a 21-year period.

Although the prospect of long-term leukemia-free survival (LFS) after treatment for adult acute lymphoblastic leukemia (ALL) is widely accepted, few studies have reported long-term survival data. Three hundred and seventy-eight ALL patients, referred to our hospital from 1978 to 1999, were reviewed for long-term follow-up data. The analysis included data on 351 patients treated by standard chemotherapy according to 11 different successive and/or concomitant regimens. Complete remission (CR) was achieved in 299 patients (79%). Initial performance status, LDH level, immunophenotype, age, and risk group (defined according to Hoelzer's criteria) at diagnosis were of significant prognostic value for CR achievement. Median leukemia-free survival (LFS) was 14 months with a 3-year, a 5-year, and an 8-year LFS at 30%, 26%, and 24%, respectively. LFS was better in T cell lineage ALL than in B cell lineage ALL (P = 0.05). Younger age was also a favorable prognostic factor for LFS (P = 0.001). Philadelphia-positive (Ph+) ALL displayed a poor outcome since median LFS was 7 months with only 13% of survival at 3 years. Median overall survival (OS) of the entire cohort was 18 months with a 3-year, a 5-year, and an 8-year OS at 32%, 24%, and 22% respectively. Favorable prognostic factors for OS were younger age (P < 0.0001), and T cell lineage ALL (P = 0.001). Among non-T cell lineage ALL, standard-risk ALL confirmed a significant better outcome than high-risk ALL (P = 0.0003). It was apparent from this analysis that hazard rates for death and relapse were greatest in the first year, decreased substantially between years 1 and 2, then decrease further between years 2 and 3. Rates of death and relapse were quite low after 3-4 years. All patients relapsing after 3 years of CR were B or non-B non-T cell lineage ALL. Long-term survivors (LTS), defined as survival in CR > or =3 years, represented 23% of evaluable patients. Eighty-three patients remain alive in initial CR at >3 years, while only three were LTS after a second CR. Overall, no significant improvement was shown in terms of CR achievement and survival duration over the years. However, regarding survival, a significant improvement was demonstrated in T cell lineage ALL (P = 0.03). Furthermore, patients (aged less than 50 years) transplanted while in first CR did significantly better than those receiving only chemotherapy as post-remission therapy (P < 0.0001). The 3-year OS, after allogeneic transplantation in first CR, was 74% in T cell lineage ALL, while it was less than 50% in B cell lineage ALL. This single center study on a large cohort of ALL patients reflects the degree to which ALL treatment remains unsuccessful in adults. Only T cell lineage ALL outcomes have improved over the years. The results suggest a time (3 years) at which it becomes reasonable to speak of potential cure, provided the patient is in CR.     

Adult acute lymphoblastic leukemia with central nervous system involvement: an overview

At the time of diagnosis, central nervous system (CNS) involvement is identified in less than 10% of adult acute lymphoblastic leukemia (ALL). Long-term disease-free survival can be achieved in these patients. CNS disease at presentation does not appear to be an independent poor prognostic factor. In CNS leukemia, innovative treatments and alternative delivery techniques are, however, warranted. Outcome in such patients is a reflection of an aggressive systemic and CNS-directed therapy. However, CNS toxicity represents the dose-limiting side effect of treatment. With effective CNS prophylaxis including intrathecal chemotherapy, high-dose systemic administration of certain agents and cranial irradiation, most adults with ALL without CNS disease at diagnosis may remain free of CNS leukemia. CNS involvement at the time of relapse occurs in 1 to 15% of cases. Leukemic relapse remains a major therapeutic challenge. Adult ALL with CNS recurrence remains of poor prognosis and is generally associated with a systemic and medullary relapse.     

Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial.

PURPOSE: We analyzed the benefits of a risk-adapted postremission strategy in adult lymphoblastic leukemia (ALL), and re-evaluated stem-cell transplantation (SCT) for high-risk ALL. PATIENTS AND METHODS: A total of 922 adult patients entered onto the trial according to risk groups: standard-risk ALL (group 1), high-risk ALL (group 2), Philadelphia chromosome-positive ALL (group 3), and CNS-positive ALL (group 4). All received a standard four-drug/4-week induction course. Patients from group 1 who achieved a complete remission (CR) after one course of induction therapy were randomly assigned between intensive and less intensive postremission chemotherapy, whereas those who achieved CR after salvage therapy were then included in group 2. Patients in groups 2, 3, and 4 with an HLA-identical sibling were assigned to allogeneic SCT. In groups 3 and 4, autologous SCT was offered to all other patients, whereas in group 2 they were randomly assigned between chemotherapy and autologous SCT. RESULTS: Overall, 771 patients achieved CR (84%). Median disease-free survival (DFS) was 17.5 months, with 3-year DFS at 37%. In group 1, the 3-year DFS rate was 41%, with no difference between arms of postremission randomization. In groups 2 and 4, the 3-year DFS rates were 38% and 44%, respectively. In group 2, autologous SCT and chemotherapy resulted in comparable median DFS. Patients with an HLA-matched sibling (groups 2 and 4) had improved DFS. Three-year DFS was 24% in group 3. CONCLUSION: Allogeneic SCT improved DFS in high-risk ALL in the first CR. Autologous SCT did not confer a significant benefit over chemotherapy for high-risk ALL.     

High survival rate in infant acute leukemia treated with early high-dose chemotherapy and stem-cell support. Groupo Espa?ol de Trasplante de Médula Osea en Ni?os.

PURPOSE: Infants with acute leukemia have a poor prognosis when treated with conventional chemotherapy. It is still unknown if stem-cell transplantation (SCT) can improve the outcome of these patients. In the present study, we review our experience with SCT in infant acute leukemia to clarify this issue. PATIENTS AND METHODS: We report the results of 26 infants who were submitted to a SCT for acute leukemia. There were 15 cases of acute myeloid leukemia and 10 cases of acute lymphoid leukemia. One patient had a bilineal leukemia. Twenty-two patients were in their first complete response (CR1), three were in their second CR, and one was in relapse. Eight patients were submitted to allogeneic SCT, and 18 underwent autologous SCT. RESULTS: With a median follow-up of 67 months, the 5-year overall survival and disease-free survival (DFS) are 64% (SE = 9%) and 63% (SE = 10%), respectively. Autologous and allogeneic SCT offered similar outcome. There was not any transplant-related mortality, and all deaths were caused by relapse in the first 6 months after SCT. In multivariate analysis, the single factor associated with better DFS was an interval between CR1 and SCT of less than 4 months (P: <.025). CONCLUSION: SCT is a valid option in the treatment of infant acute leukemia, and it may overcome the high risk of relapse with conventional chemotherapy showing very reduced toxicity. This study suggests that SCT should be performed in CR1 in the early phase of the disease.     

Central nervous system relapses after bone marrow transplantation for acute lymphoblastic leukemia in remission

This study defines the risk of central nervous system (CNS) relapse in patients undergoing bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL) in remission, with no posttransplant prophylactic CNS therapy. Ninety-two consecutive patients in complete remission received BMT for ALL (n = 82) or high-grade non-Hodgkin's lymphoma with poor prognostic factors at diagnosis (n = 10). Sixty-six patients received allogeneic BMT (Allo-BMT) and 26 patients, without an identical sibling, underwent autologous BMT (Auto-BMT). Fifteen patients had CNS involvement at diagnosis and underwent BMT in first remission. Eight patients experienced CNS relapse after BMT, corresponding to a probability of 11% at 3 years. Apart from a history of prior CNS involvement, no patient characteristic evaluated statistically influenced CNS relapse after BMT. The probability of CNS relapse was 5.5% for the 70 patients without history of CNS involvement and 27.5% for the 22 patients with prior CNS involvement. However, subgroup analysis showed that the increased risk of CNS relapse is mainly observed in Auto-BMT patients with history of prior CNS involvement, particularly in patients undergoing BMT in first remission (three of five Auto-BMT versus one of ten Allo-BMT). Taking into account the multiple factors which influence the occurrence and the treatment of CNS leukemia, the results on this retrospective study suggests that (1) for patients without CNS involvement at diagnosis and for whom BMT is performed in first remission, cranial irradiation before BMT and posttransplant prophylactic CNS therapy can be omitted because of the low probability of CNS relapse after BMT (3.4%), when total-body irradiation (TBI) is included in the conditioning regimen; and (2) the difference observed between Allo-BMT and Auto-BMT patients with previous CNS involvement and undergoing BMT in first remission could indicate that graft-versus-host leukemia acts even in the CNS in Allo-BMT patients.     

Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study.

In order to improve the disappointing prognosis of adult patients with acute lymphoblastic leukemia (ALL), we applied similar induction therapy as that used for acute myeloid leukemia (AML), ie frequent administration of doxorubicin (DOX). DOX 30 mg/m(2) was administered from days 1 to 3 and from days 8 to 10 together with vincristine, prednisolone, cyclophosphamide and L-asparaginase, followed by three courses of consolidation and four courses of intensification. From December 1993 to February 1997, 285 untreated adult patients with de novo ALL were entered. Of 263 evaluable patients (age 15 to 59; median 31), 205 (78%) obtained complete remission (CR). At a median follow-up period of 63 months, the predicted 6-year overall survival (OS) rate of all patients was 33%, and disease-free survival (DFS) rate of CR patients was 30%, respectively. By multivariate analysis, favorable prognostic factors for the achievement of CR were age <40 and WBC <50 000/microl; for longer OS were age <30 and WBC <30 000/microl; and for longer DFS of CR patients were FAB L1 and ALT <50 IU/l. Among 229 patients who had adequate cytogenetic data, 51 (22%) had Philadelphia (Ph) chromosome. Ph-negative chromosome was a common favorable prognostic factor for CR, longer OS and DFS. DFS was not different between early sequential intensification (n = 48) and intermittent intensification (n = 43) during the maintenance phase. Among CR patients under 40 years old, the 6-year survival was not different between the allocated related allo-BMT group (34 patients) and the allocated chemotherapy group (108 patients). However, among patients with Ph-positive ALL, the survival of patients who actually received allo-BMT was superior to that of patients who received chemotherapy (P = 0.046).     

Outcome of treatment with Hyper-CVAD regimen in Chinese patients with acute lymphocytic leukemia

Modern intensive chemotherapy regimens have improved the prognosis for adult patients with acute lymphocytic leukemia (ALL). With these regimens, the complete response (CR) rates are approximately 75% and long-term disease-free survival (DFS) rates are about 20-35%. For patients with high-risk ALL, DFS rates are only 20% or less. Hyper-CVAD regimen is effective in ALL and aggressive non-Hodgkin lymphomas (NHL) with increased CR rates and DFS rates. Between June 2002 and October 2006, 53 consecutive adult patients with newly diagnosed adult ALL were treated with Hyper-CVAD regimen for six to eight cycles. The alternating courses were given every 3-4 weeks or earlier if count recovery occurred. CR rates of 73.6% were achieved in 39 patients, the estimated 2-year survival rate was 82.9% and the estimated 2-year event-free survival (EFS) rate was 87.3%. Side effects were as expected, mostly attributed to myelosuppression. Analysis of prognostic factors suggested that some previously well-established poor prognostic factors such as the degree of leukocytosis and central nervous system (CNS) or testicular involvement were less important with this dose-intensive regimen. However, patients with mediastinal disease had lower CR rates (P<0.05), with the presence of hepatomegaly and t(9;22) abnormalities had poor survival (P<0.05). Compared with other established adult ALL regimens, Hyper-CVAD regimen was associated with significantly better CR rates, overall survival and EFS rates. The long-term follow-up results of Hyper-CVAD were favorable.     

Dose intensification of daunorubicin and cytarabine during treatment of adult acute lymphoblastic leukemia

BACKGROUND:

Cancer and Leukemia Group B (CALGB) Study 19802, a phase 2 study, evaluated whether dose intensification of daunorubicin and cytarabine could improve disease‐free survival (DFS) in adults with acute lymphoblastic leukemia (ALL) and whether high‐dose systemic and intrathecal methotrexate could replace cranial radiotherapy for central nervous system (CNS) prophylaxis.

METHODS:

One hundred sixty‐one eligible, previously untreated patients ages 16 to 82 years (median age, 40 years) were enrolled, and 33 (20%) were aged ≥60 years.

RESULTS:

One hundred twenty‐eight patients (80%) achieved complete remission (CR). Dose intensification of daunorubicin and cytarabine was feasible. At a median follow‐up of 10.4 years for surviving patients, the 5‐year DFS rate was 25% (95% confidence interval, 18%‐33%), and the overall survival (OS) rate was 30% (95% confidence interval, 23%‐37%). Patients aged <60 years who received the 80 mg/m² dose of daunorubicin had a DFS of 33% (95% confidence interval, 22%‐44%) and an OS of 39% (95% confidence interval, 29%‐49%) at 5 years. Eighty‐four patients (52%) relapsed, including 9 patients (6%) who had isolated CNS relapses. The omission of cranial irradiation did not result in higher than historic CNS relapse rates.

CONCLUSIONS:

Intensive systemic, oral, and intrathecal methotrexate dosing permitted the omission of CNS irradiation in adult patients with ALL. This intensive approach using higher doses of daunorubicin and cytarabine failed to result in an overall improvement in DFS or OS compared with historic CALGB studies. Future therapeutic strategies for adults with ALL should be tailored to specific age and molecular genetic subsets. Cancer 2013. © 2012 American Cancer Society.     

Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia

BackgroundThe use of imatinib combined with chemotherapy has demonstrated improved outcome in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). However, a substantial proportion of patients continue to die as a result of disease progression.Patients and methodsWe assessed the minimal residual disease (MRD)-based effect and long-term outcome of first-line incorporation of dasatinib (100 mg once daily) into chemotherapy alternatively for adults with Ph-positive ALL. The primary end point was the major molecular response (MMR) rate by the end of the second dasatinib cycle. Patients with a donor proceeded to allogeneic stem cell transplantation (SCT) as early as possible. MRD monitoring was centrally evaluated by real-time quantitative polymerase chain reaction (4.5-log sensitivity) using bone marrow samples.ResultsFifty-one patients (median age, 46 years) were enrolled and treated with this strategy. After the first dasatinib cycle, 50 patients (98.0%) achieved complete remission (CR). By the end of the second dasatinib cycle, 46 (93.9%) of 49 assessable patients had persistent CR, and 38 (77.6%) had MMR (32.7%) or undetectable MRD (44.9%). On the basis of the MRD kinetics by this time point, the numbers of early-stable, late, and poor molecular responders were 23 (46.9%), 15 (30.7%), and 11 (22.4%), respectively. Thirty-nine patients (76.5%) underwent allogeneic SCT in CR1. After a median follow-up of 54 months, the 4-year cumulative incidence of relapse and disease-free survival (DFS) rate for all patients were 30.0% and 52.0%, respectively, and the corresponding outcomes among those receiving allogeneic SCT in CR1 were 20.5% and 64.1%, respectively. Poor molecular responders had a higher risk of relapse and DFS than those of early-stable molecular responders.ConclusionThis dasatinib-based protocol was effective for achieving a good quality molecular response and durable DFS in adults with Ph-positive ALL.Trial registrationclinicaltrials.gov, NCT01004497.     

Survival Rates of Adults With Acute Lymphoblastic Leukemia in a Low-Income Population: A Decade of Experience at a Single Institution in Mexico

BackgroundThe therapeutic progress for adults with acute lymphoblastic leukemia (ALL) has been slow, with a 5-year survival of 30% to 45% in developed countries. Scarce information is available regarding the treatment and survival rates from nonindustrialized populations. In the present study, the characteristics of adults with ALL at a single institution were documented.Patients and MethodsThe clinical files of patients aged ≥ 18 years who had been diagnosed with ALL from 2005 to 2015 at a reference center in Mexico were scrutinized. Overall survival (OS) and event-free survival (EFS) were determined using the Kaplan-Meier method. The hazard ratios for death and relapse were estimated using Cox regression analysis.ResultsA total of 94 adults were included. Their median age was 33 years; 69 (73.4%) had high-risk and 25 (26.6%) had standard-risk ALL. Of the 94 patients, 67 (71.3%) achieved complete remission (CR), 20 (21.3%) experienced disease resistance, and 7 (7.4%) died early during induction to remission, mainly of sepsis. The 5-year EFS and OS was 23.4% and 31.1% for the whole group and 24.9% and 38.9% for patients who achieved CR, respectively. Of the 94 patients, 50 (43.9%) died of sepsis or disease progression. Relapse developed in 43 patients (45.7%). The median survival after relapse was 6.93 months. Bone marrow was the most frequent site of relapse (21 patients [48.8%]) and conferred a significantly lower 5-year OS of 16.4%.ConclusionAdults with ALL in Mexico had high-risk characteristics and an increased relapse rate; however, the OS after CR was similar to the greatest achieved in developed countries, suggesting that a threshold for curing adult ALL with current therapeutic strategies has been reached.     

Bone marrow leukemic progenitor cell content in pediatric T-lineage acute lymphoblastic leukemia patients with an isolated extramedullary first relapse.

Isolated extramedullary relapse in childhood acute lymphoblastic leukemia (ALL) is associated frequently with the T-lineage immunophenotype and may be accompanied by occult bone marrow disease. We employed highly sensitive multiparameter flow cytometry and blast colony assays to quantify the leukemic progenitor cell (LPC) burden in the pretreatment bone marrows of 15 pediatric T-lineage ALL patients with an isolated extramedullary first relapse. Sites of extramedullary relapse were CNS (11 patients), testes (3 patients), and both CNS and testes (1 patient). Bone marrow LPC were detectable in 8 patients (53%) and undetectable in 7 patients (47%) at day 0 of post-relapse induction therapy, with LPC counts ranging from 0/10(6) mononuclear cells (MNC) to 518/10(6) MNC (mean +/- SEM, 50+/-34/10(6) MNC). Five of 9 patients with an early relapse (< 18 months after achieving a first complete remission [CR1]) and 3 of 6 patients with a late relapse (> or = 18 months from CR1) had detectable bone marrow LPC at day 0. Five of 8 patients with NCI-defined poor risk ALL and 3 of 7 patients with NCI-defined standard risk ALL had detectable LPC at day 0. Following post-relapse induction chemotherapy. LPC counts were detectable in bone marrows of 4 of 6 evaluated patients. Thus, approximately half of the extramedullary relapse T-lineage ALL patients studied had substantial occult involvement of the bone marrow. These findings may partly explain the previously observed poor prognosis of T-lineage patients following a CNS relapse.     

Total body irradiation, thiotepa, and cyclophosphamide as a conditioning regimen for children with acute lymphoblastic leukemia in first or second remission undergoing bone marrow transplantation with HLA-identical siblings.

PURPOSE: Allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA-identical siblings can be used to treat children with acute lymphoblastic leukemia (ALL). However, a significant proportion of patients with ALL who undergo HSCT relapse. For this reason, we prospectively evaluated a preparative regimen that included total body irradiation (TBI), thiotepa (TT), and cyclophosphamide (CY) in patients with high-risk ALL in first complete remission (CR) and in children with ALL in second CR. PATIENTS AND METHODS: Forty children (median age, 9 years; range, 1 to 18 years) with ALL in first or second CR who underwent allogeneic HSCT from HLA-identical siblings were conditioned with a combination of fractionated TBI, TT (10 mg/kg), and CY (120 mg/kg over 2 days). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine administered intravenously at a dose of 1 to 3 mg/kg/d for the first 21 days and subsequently orally at a dose of 6 mg/kg/d. RESULTS: All assessable patients were engrafted, with a median time of 11 and 24 days for neutrophil and platelet recovery, respectively. The preparative regimen was well tolerated. Only one patient died as a result of regimen-related causes. Eight patients relapsed at a median time of 8 months after transplantation (range, 3 to 9 months), and this determined a cumulative probability of relapse of 23%. Twenty-six of 40 patients (65%) are alive and in complete hematologic remission, with a median observation time of 36 months (range, 14 to 57 months), which results in a disease-free survival (DFS) at 3 years of 65%. The 13 patients who underwent transplantation in first CR had a DFS of 85%, whereas the 27 patients who underwent HSCT in second CR had a DFS of 56%. CONCLUSION: These data suggest that TT is an effective cytotoxic drug that can be safely added to the classical TBI-CY regimen. Because of its cell cycle-independent action, good CNS diffusion, and limited extramedullary toxicity, TT may contribute to increasing the percentage of children with ALL who are successfully cured with allogeneic BMT.     

Outcomes of adult patients with relapsed acute lymphoblastic leukemia following frontline treatment with a pediatric regimen

We analyzed the outcome of 46 patients with acute lymphoblastic leukemia (ALL) who relapsed following treatment with a pediatric-based protocol; 34 received intensive re-induction chemotherapy, with a CR2 rate of 62%, median overall survival (OS) 7.8 months, median relapse-free survival 5.2 months and one year OS 19%. Allogeneic HSCT was performed in 8 patients in CR2/3, with a median OS 2.2 months. OS was superior in patients who relapsed after completion of chemotherapy, compared to those relapsing on treatment. The outcome of adult ALL relapsing after treatment was therefore poor, and novel salvage strategies are needed to improve outcomes.     

Prognostic factors in adult patients with acute leukemia at first relapse

The case histories of 252 adolescent and adult patients with acute leukemia diagnosed and treated between 1975 and 1985 are analyzed with special attention to prognostic factors determining the second complete remission (CR) rate. A first CR was achieved in 65% of cases, 60% for acute myelogenous leukemia (AML), and 75% for lymphoblastic leukemia (ALL). In 86 patients a relapse occurred (50 AML, 36 ALL), and 50% of them entered a second CR after reinduction therapy. Median survival after first relapse of these reinduction-responders was significantly prolonged in comparison to the reinduction-nonresponders for both AML (15 versus 2 months) and ALL (11 versus 3 months). Median duration of the first CR of the reinduction-responders was significantly longer than that of the second CR (13 versus 6 months). The major determinant for the probability to obtain a second CR after reinduction therapy was the duration of the first CR. The latter was significantly longer in the reinduction-responders than in the nonresponding group (13 versus 5 months). Furthermore patients younger than 40 years, and those who relapsed after ending the maintenance therapy, tended to have better chances to achieve a second CR. Rapid achievement of the first CR, and sex of the patients seemed not to be of predictive value. The authors conclude that aiming for a second CR is worthwhile in young patients who relapse after a long first CR.     

Clinical Outcome of Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph + ALL): Experience From a Single Institution

To identify factors affecting transplant outcome, data from 65 Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients who had undergone allogeneic hematopoietic transplantation (allo-HSCT) in our institution were analyzed. The probability of OS (overall survival) and DFS (disease free-survival) at 3 years after allo-HSCT was 40.1 % and 38 %, respectively. Multivariate analysis showed that gender and disease status (p?=?0.0059, p?=?0.0039, respectively) were significant factors for OS. Among 51 patients with CR (complete remission), multivariate analysis showed that the factors associated with OS included gender (p?=?0.014), number of white blood cell at diagnosis (p?=?0.025), and the source of stem cells (bone marrow <BM >versus. cord blood; BM stem cell source was associated with favorable OS, p?=?0.042). Twenty-one patients relapsed after allo-HSCT with a median of 207 days (range, 19–1,324 days). The estimated cumulative incidence of relapse at 3 years was 39.4 %. Patients with CR showed a lower relapse rate at 3 years (34.2 %) when compared with patients with non-CR (62.7 %). Among 21 patients, eight patients received imatinib-based chemotherapy and 13 received chemotherapy without imatinib before HSCT. In terms of treatment after relapse, seven patients received chemotherapy with imatinib and 13 received chemotherapy without imatinib. Five patients underwent a second HSCT. One patient survived, and 20 patients died. In this study, disease status at time of allo-HSCT had a significant impact on OS, DFS, and relapse. Imatinib administration given before allo-HSCT was not associated with favorable outcome. Second-generation tyrosine kinase inhibitors may be more suitable candidates for Ph + ALL before and after allo-HSCT.     

Lower leukocytes at initial diagnosis may predict poor outcome of very late relapse of acute lymphoblastic leukemia

We have reported a rare case of acute lymphoblastic leukemia (ALL) recurring 19 years after the first presentation. Since 1984, 36 relapse cases 10 years or more after the first diagnosis have been reported. All cases were childhood ALL with a low to standard risk. Twenty-six attained CR2, and 18 of them remained in sustained CR2. The sustained CR2 ratio was 80% without transplantation. Sustained CR2 ratio was significantly lower in patients with lower leukocytes (<10 x 10(9)l(-1)) at initial presentation. A very late relapse of ALL remains chemosensitive, and its prognosis is not unfavorable.