Relapse of acute leukemia after marrow transplantation: natural history and results of subsequent therapy

Of 455 acute nonlymphocytic leukemia (ANL) patients who underwent marrow transplantation, 95 (21%) relapsed a median of 6.5 months posttransplantation and 62 received further treatment. Twenty achieved remission. Success of therapy was related to the length of time from marrow transplant to relapse and to the use of cytarabine (Ara-C) and daunomycin. Aggressive chemotherapy for patients relapsing within 100 days of marrow transplant was associated with a high incidence of early death (six of 14 patients) and a low probability of remission (one of 14). Of 23 patients who relapsed in excess of 1 year from marrow transplant, 15 achieved a complete remission. The median disease-free survival is 6 months (range, 0.4 to 53+ months). Acute lymphocytic leukemia (ALL) recurred in 130 of 366 patients (36%), and 94 received further therapy. Fifty-two achieved a remission. Remissions were more common in late relapse patients (greater than 1 year from transplantation): 65% v 7% for those relapsing within 100 days from transplant (P less than .05). Testicular relapse occurred in 11 patients and was the sole site of relapse in seven. Three are alive and free of disease 58 to 109+ months after relapse. The median survival for the treated patients is 10.5 months (range, 5 to 109+ months). We propose that reinduction be attempted in all patients relapsing greater than 1 year from marrow transplantation. Ara-C and daunomycin should be employed in the treatment of ANL. The decision for treatment of patients relapsing earlier than 1 year should be made on an individual basis.     

Alternating drug pairs with or without periodic reinduction in children with acute lymphoblastic leukemia in second bone marrow remission: a Pediatric Oncology Group Study

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) who experience hematologic recurrence while receiving chemotherapy or within 6 months after its cessation have a low cure rate. In this study (Pediatric Oncology Group Protocol 8303) two methods were examined for improving the outcome in these children. METHODS: After remission induction with prednisone, vincristine, daunorubicin, and asparaginase (PVDA) and consolidation chemotherapy with teniposide and cytarabine, patients received weekly continuation chemotherapy with rotating pairs of drugs, comprised of teniposide and cytarabine and vincristine and cyclophosphamide. In addition, they were randomized to receive or not receive repeated reinduction with PVDA. Patients with matched sibling donors were allowed to receive allogeneic bone marrow transplantation (BMT) instead of continued chemotherapy. RESULTS: Of 297 evaluable patients 258 (87%) achieved second complete hematologic remission. However, only 23 of these patients remained continuously free of leukemia > or =7 years after chemotherapy or BMT. Neither PVDA pulses nor BMT appeared to influence outcome at a statistically significant level. CONCLUSIONS: The results of the current study confirm prior reports of the low cure rate of children with ALL who experience hematologic recurrence during initial therapy or shortly after its cessation. New approaches are needed to prevent and retreat hematologic recurrence in pediatric ALL patients.     

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.     

Allogeneic bone marrow transplantation for acute lymphoblastic leukemia in remission: prolonged survival associated with acute graft-versus-host disease

Forty remission patients with high-risk acute lymphoblastic leukemia (ALL) underwent matched allogenic bone marrow transplantation (BMT) following preparation with cyclophosphamide and fractionated total body irradiation (TBI). As of March 1987, the median follow-up is more than 3 1/2 years. Thirteen patients are alive (11 relapse free) between 2 and 4 1/2 years post-BMT. Neither age, sex, remission number, prior extramedullary leukemia, nor WBC at diagnosis of ALL was statistically significant as a predictor of relapse-free survival. The development of acute graft-v-host disease (GVHD) in 17 patients was found, with time-dependent Cox regression analysis, to be associated with a significant reduction in post-BMT relapse risk (P = .04) and improved disease-free survival (P = .11). A prospective, randomized trial of maintenance chemotherapy with oral methotrexate and mercaptopurine did not demonstrate improvement in relapse risk or survival for those assigned maintenance chemotherapy (P = .7). These results suggest that allogeneic BMT can result in extended relapse-free survival for some patients with high-risk ALL. More effective preparative chemoradiotherapy and exploitation of the apparent graft-v-leukemia effect may be useful in future trials.     

Treatment results of acute leukemia in elderly patients: analysis of 61 consecutive patients in a single institution

In order to investigate the clinical characteristics and management of elderly patients with acute leukemia, we retrospectively analyzed treatment results for 61 acute leukemia patients aged 65 years or more (median age 72) admitted to our department between October 1995 and September 2006. There were 6 elderly patients with ALL (acute lymphocytic leukemia) and 55 patients with AML (acute myelogenous leukemia). Among them, 51 patients could receive chemotherapy, but 10 patients received symptomatic therapy only. Complete remission was achieved in 50% of 46 patients who received chemotherapy, and median overall survival was 237 days. We analyzed treatment results for AML patients who underwent chemotherapy as follows. The intensive chemotherapy group and the de novo leukemia group showed a significantly higher CR rate and longer survival. No differences were found in karyotype, performance status or complications. Intensive chemotherapy was effective for 65-74-year-old patients with de novo AML. In future, we consider that the prognosis for elderly patients with acute leukemia will improve, if made-to-order treatment is given, depending on evidence-based stratification of patients with organs having low reserve capacity.     

Evaluation of levamisole as an adjuvant to chemotherapy for treatment of ANLL

Levamisole is a synthetic, orally administered, relatively nontoxic compound with immunorestorative ability. Levamisole was tested in this study of 60 adults with acute nonlymphocytic leukemia (ANLL) to determine if augmentation of response rate or duration, or survival over that obtained with a standard chemotherapy regimen alone would result. The chemotherapy regimens for all patients consisted of daunorubicin and cytosine arabinoside for induction and consolidation, methotrexate with citrovorum factor reversal in a cytoreductive phase, and late intensification with thioguanine and cytosine arabinoside. The first 30 patients received chemotherapy alone; a second group of 30 patients were scheduled to receive levamisole in addition to chemotherapy. Levamisole, 45 mg/m2, was administered orally twice daily for three consecutive days each week beginning one week after the initiation of induction chemotherapy and continuing until relapse. No significant difference emerged between the two groups with respect to remission rate, time to achieve remission, postrelapse survival, or total survival. However, a trend towards improved postcomplete remission survival (P = 0.072) was noted in the levamisole group, and patients who received levamisole had a significantly greater reinduction rate after relapse (P = 0.019).     

Aggressive Chemotherapy for Acute Leukemia Relapsed After Transplantation

Bone marrow transplantation procedure has emerged as an effective treatment for hematological malignancies. However, recurrence of leukemia is still the major cause of treatment failure. Subsequent treatment in this category of patients, generally considered incurable, has not been yet standardized. At our institution, 13 patients, 7 with acute non lymphoid leukemia (ANLL) and 6 with acute lymphoid leukemia (ALL), were treated at relapse after bone marrow transplantation either autologous or allogeneic (AuBMT 8, ABMT 4) performed in complete remission (CR). The interval between BMT and relapse was less than 9 months in 6 patients (2 ABMT and 4 AuBMT) and more than 9 months in 7 patients. Early relapsed patients showed no response to treatment and died at a median of 5.5 months (range 1-13) after relapse. Late relapse after BMT was characterized by a high percentage of response (5 CR and 1 PR), particularly after intensive chemotherapy and by a longer survival (median 14 months; range 2-36).

Chemotherapy after transplantation should be carefully evaluated in patients relapsed after BMT in order to select a population that can achieve long term disease free survival.     

Role of interleukin-2 in human hematological malignancies

Clinical studies with Interleukin-2 (IL-2) in human hematologic malignancies were initiated in the late 1980s. Based on clinical studies on various solid tumors, and laboratory research on hematopoietic cells, IL-2 was shown to be effective in 150 acute myeloid leukemia (AML) patients mainly for maintenance therapy in first complete remission, or with residual blast cells in the marrow. IL-2 has also been shown to be effective in remission induction in 10 patients with chronic myeloid leukemia (CML). The role of IL-2 in lymphoma patients remains to be established. IL-2 alone or in combination with Interferon-α, may intensify remission and prolong disease-free survival when given post autologous bone marrow transplantation (BMT) to patients with lymphoma and myeloid leukemia, and to a lesser degree, to patients with acute lymphatic leukemia (ALL). IL-2 in combination with HLA-matched or mismatched peripheral blood lymphocytes was also used post autologous BMT in preliminary studies. IL-2 was administered with or without peripheral blood lymphocytes, for prevention of relapse post T-cell-depleted allogeneic BMT in CML, ALL and AML, with encouraging results. The same strategy was shown to be effective in the reinduction of remission in patients with CML, who relapsed post BMT.     

Outcome in children with relapsed acute myeloid leukemia after initial treatment with the French Leucemie Aique Myeloide Enfant (LAME) 89/91 protocol of the French Society of Pediatric Hematology and Immunology.

PURPOSE: After present first-line therapies for childhood acute myeloid leukemia (AML), nearly 40% of patients still relapse. The goals of this retrospective study were to determine whether these children could be treated successfully with a salvage regimen and to establish the optimal therapeutic strategy. PATIENTS AND METHODS: In the multicentric, prospective, Leucémie Aiqu? Myélo?de Enfant 89/91 protocol, 106 of the 308 children enrolled between 1988 and 1998 relapsed. Initial treatment after the first complete remission (CR1) had been allogenic HLA-identical bone marrow transplantation (BMT; n = 21) or chemotherapy (n = 85). Treatment procedures were scheduled according to the choice of each participating institution. RESULTS: When reinduction therapy was attempted, second complete remission (CR2) was obtained in 71% of patients (68 of 96 patients). BMT was performed in 53 (78%) of these 68 patients (autograft, mainly harvested in CR1, n = 25; matched sibling-donor BMT, n = 12; or alternative-donor BMT, n = 16). The 5-year overall survival (OS) rate for all 106 patients was 33%, and the disease-free survival (DFS) rate for children in CR2 was 45%. Multivariate analysis of re-treated children showed that the 5-year OS was higher if the CR1 had been longer than 12 months compared with less than 12 months (54% v 24%, respectively; P =.001) and lower if maintenance therapy had been given after CR1 compared with chemotherapy without maintenance therapy or HLA-identical BMT (12% v 40% v 52%, respectively; P =.002). For patients attaining CR2, the 5-year DFS rate was not significantly different for matched sibling-donor BMT (60%), autograft (47%), or alternative-donor BMT (44%). CONCLUSION: After aggressive first-line therapy, one third of unselected, relapsing AML children could be cured. Further prospective trials are warranted to define the optimal reinduction regimen and megadose chemotherapy and to evaluate the late effects of these therapies.     

Comparison of the survivals between bone marrow transplantation and chemotherapy for acute leukemia in first remission--a Japanese single institution study.

The outcome of sixty-four patients with acute leukemia in first remission who had been treated with either bone marrow transplantation (BMT) or conventional chemotherapy was retrospectively evaluated (a median follow-up of 37 months). Among them, 26 patients (age range; 14-42 years) received allogeneic BMT from HLA-identical siblings and 38 patients (age range; 13-43 years) who had no HLA-identical donors undertook the continued combination chemotherapy. Kaplan-Meier product-limit estimate of actuarial survival of acute myelogenous leukemia (AML) patients was 48.9% for the BMT group and 15.7% for the chemotherapy group (p = not significant, NS). For acute lymphoblastic leukemia (ALL) patients, the survival following BMT was 80.2% and was significantly higher than that of the chemotherapy group of 33.3% (p < 0.05). The disease-free survival of AML and ALL for the BMT group was 34.3% and 36.5%, respectively, which was higher than that of the chemotherapy group (16.7% and 23.4%, respectively (p = NS)). These findings in our Japanese single institution study suggested that BMT may be the treatment of choice for adult patients with acute leukemia in first remission if they had suitable donors and that more effective therapeutic regimens were necessary for patients without compatible donors in order to obtain the longer remission duration.     

Low-dose cytarabine maintenance therapy vs observation after remission induction in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial (E5483).

The Eastern Cooperative Oncology Group (ECOG) conducted a prospective phase III study in patients with relapsed/refractory acute myeloid leukemia (AML) to evaluate whether administration of repeated courses of low-dose cytarabine (LDAC) maintenance therapy after induction of complete remission in advanced AML would improve disease-free and overall survival. Patients with AML in second/later relapse or refractory disease were first treated with a combination of high-dose cytarabine and amsacrine. Those who achieved complete remission were then randomized to observation or to receive LDAC, 10 mg/m2 subcutaneously twice a day x2 21 days every 2 months until relapse occurred. Of 86 patients eligible for randomization, 41 patients were assigned to receive LDAC and 45 patients to observation. The median disease-free survival was 7.4 months for patients assigned to LDAC compared to 3.3 months for patients receiving no additional therapy, P= 0.084. The median survival from randomization was 10.9 months and 7.0 months for patients receiving LDAC maintenance chemotherapy and observation, respectively (P= 0.615). The data from this study suggest that LDAC maintenance therapy given to patients with advanced AML who achieve complete remission can increase disease-free survival compared to observation, but does not improve overall survival. Nevertheless, because of the ineffectiveness and toxicity of intensive post-remission chemotherapy in this circumstance, LDAC maintenance therapy, a tolerable outpatient regimen, offers the potential for improved quality of life.     

Risk and prognosis of central nervous system leukemia in patients with Philadelphia chromosome-positive acute leukemias treated with imatinib mesylate.

PURPOSE: In patients with acute leukemias, a lymphoid phenotype, the presence of a Philadelphia chromosome (Ph), and inadequate central nervous system (CNS)-directed prophylactic therapy are risk factors for CNS involvement. Imatinib mesylate has promising single-agent antileukemic activity in patients with advanced Ph(+) acute leukemias. It was the aim of this analysis to determine the incidence of, and risk factors associated with, meningeal leukemia during imatinib monotherapy. STUDY DESIGN: We analyzed 107 consecutive patients with relapsed or refractory Ph(+) acute lymphoid leukemia (ALL; n = 65) or chronic myeloid leukemia blast crisis (n = 42) who were enrolled in successive Phase II trials of single-agent imatinib and who did not receive routine prophylactic intrathecal chemotherapy. RESULTS: CNS leukemia developed in 13 of 107 patients (12%) and was associated primarily with a lymphoid or bilineage phenotype (12 of 78; 15%) and with imatinib refractory Ph(+) ALL (5 of 19; 26%). Meningeal leukemia did not occur among patients who received prior prophylactic cranial irradiation. The median survival with combined CNS and systemic disease was 108 days (range, 58-141), with no patient surviving long term. In contrast, two of three patients with exclusively meningeal leukemia achieved prolonged molecular remissions with intrathecal chemotherapy, cranial irradiation, and continued imatinib. CONCLUSIONS: Patients with Ph(+) ALL are at considerable risk of meningeal leukemia during imatinib monotherapy and should routinely receive CNS prophylaxis. Although the prognosis with combined meningeal and systemic relapse is dismal, patients with an isolated meningeal relapse may still achieve sustained remissions. The optimal type of CNS-directed treatment and the extent of protection afforded by prophylactic cranial irradiation remain to be defined.     

Improved treatment results in boys with overt testicular relapse during or shortly after initial therapy for acute lymphoblastic leukemia. A Pediatric Oncology group study

Boys with acute lymphoblastic leukemia (ALL) who have overt testicular relapse (OTR) during initial continuation chemotherapy or within 6 months thereafter have poor outcomes, with long-term survival similar to patients with marrow relapse during treatment. In April 1983, the Pediatric Oncology Group (POG) adopted for these patients an intensive treatment protocol (POG 8303) consisting of a four-drug systemic reinduction (prednisone, vincristine, daunorubicin, and asparaginase), a brief intensive consolidation phase with teniposide and cytarabine, and a 2-year program of continuation chemotherapy with weekly rotating drug pairs (vincristine/cyclophosphamide and teniposide/cytarabine) with or without (by randomization) four-drug reinforcement pulses every 16 weeks. Bilateral testicular radiation (2600 cGy) was administered during reinduction, and intrathecal chemoprophylaxis was given every 4 to 6 weeks. Among 38 eligible study patients with OTR, 5 had prior or concominant extramedullary relapse in other sites. The median duration of complete remission before OTR was 27 months (range, 10 to 42 months). All 38 patients achieved clinical remission after reinduction. Three patients withdrew while in remission, 22 had another relapse (12 marrow, 5 central nervous system (CNS), 2 testicular, 1 retroperitoneal, 1 prostate, and 1 eye), and 13 (34%) remain in complete remission from 32+ to 74+ months after OTR (median, 53+ months). Eighteen patients had their therapy electively discontinued, and five relapses occurred thereafter. These results are superior to those observed in patients with first marrow relapse treated with the same protocol. Approximately one third of patients with OTR treated with POG protocol 8303 exhibit prolonged second remissions with the potential for cure.     

Treatment of adult patients with acute lymphocytic leukemia in relapse

Thirty-eight patients with a diagnosis of relapsed acute lymphocytic leukemia were accrued to a treatment program of reinduction therapy by the Eastern Cooperative Oncology Group (ECOG). A combination of mitoxantrone, etoposide (VP-16), and high-dose cytarabine (ARA-C) were administered over a five day period. Thirty-four patients were eligible for follow-up subsequent to treatment. Twenty-seven patients were in first relapse and seven were in second relapse. Fifteen of the thirty-four patients treated were given two cycles of induction chemotherapy. The complete remission (CR) rate for the entire group treated was 17%. The median duration of the CR was 2.4 months and the estimated median survival for first relapse patients was 4.5 months and 5.0 months for second relapse patient group. There were five deaths attributable to toxicity associated with the chemotherapy. The study emphasizes the difficulty in achieving durable remissions in adult patients with relapsed ALL.     

A randomized comparison of maintenance treatment with androgens, immunotherapy, and chemotherapy in adult acute myelogenous leukemia. A Leukemia-Lymphoma Group Trial of the EORTC

Twenty-three European centers participated in a randomized clinical trial (AML-5) to study the effect of androgens and immunotherapy during maintenance in adult acute myelogenous leukemia. Induction treatment consisted of Adriamycin (doxorubicin) 50 mg/m2 day 1, vincristine VCR 1 mg/m2 day 2, and cytosine arabinoside 80 mg/m2 every 12 hours by push injection days 3-9. Patients in complete remission were randomized into four groups: (1) 6-mercaptopurine 70 mg/m2 days 1-14, methotrexate 15 mg/m2 twice weekly days 15-28, and reinduction with daunorubicin 35 mg/m2 and vincristine 1 mg/m2 day 29; (2) chemotherapy as in group 1 plus stanozolol 0.15 mg/kg/day; (3) 6-thioguanine 70 mg/m2 orally on 4 consecutive days and cytosine arabinoside 80 mg/m2 subcutaneously day 5 every week; and (4) chemotherapy as in Group 3 plus irradiated blast cells treated with neuraminidase. Three hundred forty-eight patients were eligible and 295 were evaluable. The median age was 45 yrs. A complete remission was achieved in 64% of the patients, with 158 complete remissions randomized. Patients not randomized and patients receiving bone marrow transplantation (BMT) were analyzed separately. There was no difference in disease-free survival (DFS) or survival in the four maintenance arms. For patients reaching complete remission, the median DFS was 40 weeks, and median survival was 22 months with 30% surviving at 4 years. The overall survival was 18% at 4 years. There was no beneficial effect for DFS or survival by adding either immunotherapy or androgens to chemotherapy during maintenance. However, patients receiving immunotherapy seemed to have a higher rate of responses to reinduction after relapse than those in the other treatment arms.     

Effect of protracted high-dose L-asparaginase given as a second exposure in a Berlin-Frankfurt-Münster-based treatment: results of the randomized 9102 intermediate-risk childhood acute lymphoblastic leukemia study--a report from the Associazione Italiana Ematologia Oncologia Pediatrica.

PURPOSE: To assess in a randomized study the therapeutic effect of the addition of high-dose L-asparaginase (HD ASP) in the context of a Berlin-Frankfurt-Münster (BFM)-based chemotherapy regimen for intermediate risk (IR) childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: From March 1991 to April 1995, a total of 705 patients, with 59% of the cohort of patients fewer than 15 years old, with newly diagnosed non-B ALL, enrolled onto the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) ALL-91 study, were assigned to the IR group. Patients in remission at the beginning of the reinduction phase were randomized either to the standard treatment (SD ASP arm) or the experimental treatment (HD ASP arm; weekly intramuscular administration of HD ASP 25,000 IU/m(2) repeated for a total of 20 weeks). Most of the patients (90%) were treated with Erwinia chrysanthemi L-asparaginase product. RESULTS: Among the 610 patients randomized to the SD ASP arm (n = 322) or to the HD ASP arm (n = 288), relapse occurred at a median time of 24 months after randomization in 76 (24%) and in 64 children (22%), respectively. Most of the relapses occurred in the marrow (100 isolated, 21 combined). There was no significant difference between the disease-free survival in the two treatment arms (P =.64), with estimated values at 7 years from randomization of 72.4% (SE 3.1) v 75.7% (SE 2.6) in the SD ASP and HD ASP arms, respectively. CONCLUSION: No advantage was observed for IR ALL children treated with BFM-based intensive chemotherapy who received protracted E chrysanthemi HD ASP during reinduction and the early continuation phase.     

Intensive retreatment of adults and children with acute lymphoblastic leukemia.

Twenty-three patients (16 adults) failing their first or subsequent (n = 8) intensive treatment for de novo acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia lymphoid blast phase (n = 2) were managed with protocol POG 8201, originally introduced in relapsed ALL of childhood. In this programme, a four-drug induction phase is followed by early consolidation with teniposide-cytarabine, intrathecal chemotherapy, continuation weekly chemotherapy alternating teniposide-cytarabine with vincristine-cyclophosphamide, and periodic reinduction courses. Fourteen adults and five children with ALL achieved a complete response (CR) (86 per cent). The highest response rate (100 per cent) was obtained in 12 patients treated at first relapse after an initial CR of greater than 18 months (p = 0.07). Median duration of CR was 8 months in adults and 11 months in children. A longer than previous one CR (inversion) was obtained in four cases. Four ALL patients were successfully transplanted from a matched sibling after 3-11 months from achievement of CR. Median overall survival in adults with ALL was 11 months, significantly longer than for 40 comparable cases treated intensively but without rotational continuation therapy in previous years (p less than 0.001). This regimen is applicable to adults with relapsed ALL, where prolongation of survival may allow time for effective salvage with bone marrow transplantation.     

Immunotherapy of acute myeloid leukaemia. Medical Research Council.

Seventy-one patients suffering from acute myeloid leukaemia (AML) who were already in complete remission and had already received one further course of cytotoxic drugs as consolidation therapy were randomised to receive maintenance chemotherapy alone or the same maintenance chemotherapy plus immunotherapy with BCG and irradiated allogeneic blast cells. The duration of first remission was slightly, but not significantly, longer in those patients who received immunotherapy. This was true also for the duration of survival after relapse. Comparison with other series suggested that the effect of such immunotherapy on duration of survival after relapse is probably real, but did not clearly indicate whether or not any real difference in the first remission duration existed.     

Outcome of patients less than 55 years of age with high-risk acute leukemia who did not have an human leukocyte antigen-identical related donor: a long-term study of 97 consecutive patients.

Between January 1993 and December 2000, an unrelated donor search (UDS) was initiated for 97 consecutive patients [46 acute lymphoblastic leukemia (ALL) and 51 acute myeloid leukemia (AML)]. Leukemia was considered to be of poor prognosis in cases of refractory disease (n=70), unfavourable karyotype (n=22) or miscellaneous (n=5). All patients had previously received various chemotherapies and 9 had undergone an autologous stem cell transplantation (SCT). The median age at UDS initiation was 25 (range 2.7-55) years. The median time to identify a suitable living donor or cord blood (CB) was 60 days. Eventually, 33 patients received unrelated allo-SCT (including 9 CB), 12 auto-SCT, 39 chemotherapy and 13 palliative treatment. At a median of 54 months, 18 patients were alive, including 15 in remission. The 4-year overall survival rates were 32%, 37%, 15% and 0% for allo-SCT, auto-SCT, chemotherapy or palliative treatment, respectively. Patients who received either allo- or auto-SCT had better survival than those who did not (P<0.0001). For ALL, only allo-SCT significantly improved survival (P<0.007). Finally, patients who received allo-SCT died less often of relapse than patients who did not (P<0.0001). Unrelated allo-SCT gives a substantial long-term survival and cure in patients with high-risk acute leukemia. For patients who achieve remission and for whom UDS fails, auto-SCT may prove to be a good approach. For patients who fail to enter into remission, intensive salvage chemotherapy has a very limited effect.     

Lymphocyte recovery after allogeneic bone marrow transplantation predicts risk of relapse in acute lymphoblastic leukemia.

Allogeneic blood and marrow transplantation (BMT) is curative for many patients with high-risk and relapsed acute lymphoblastic leukemia (ALL). However, relapse is an important cause of post-transplantation failure, and there are no reliable markers to predict relapse. A retrospective review of patients with ALL who underwent matched related allogeneic BMT was carried out to examine whether the rate of lymphocyte recovery after transplantation had any prognostic value in ALL. The absolute lymphocyte count (ALC) at days 21 and 30 after transplantation was obtained for 43 patients who received transplants during an 18-year period. Patients with an ALC of 175 x 10(6)/l or less on day 21 were more likely to relapse than those with ALC greater than 175 x 10(6)/l (relative risk, 4; 95% confidence interval, 1.5-11.2). Patients with slower lymphocyte recovery had significantly lower relapse-free survival than those with faster recovery (P=0.0028). There was also a trend toward poorer overall survival among those with a slow lymphocyte recovery (log-rank test; P=0.028). The rate of lymphocyte recovery is prognostic in patients with ALL undergoing allogeneic BMT, and this should be integrated with other predictors to identify patients at high risk of relapse. Such patients could be considered for interventions aimed at prevention of relapse, including rapid withdrawal of immunosuppressive medication or donor lymphocyte infusion.