Leukemia relapse in host cells 5 years after bone marrow transplantation for acute non-lymphocytic leukemia in first complete remission

A case of leukemia relapse in a 15-year-old girl occurring 5 years after successful allogeneic bone marrow transplantation for acute non-lymphocytic leukemia is reported. Laboratory findings demonstrated that this relapse was in host cells and had the same phenotype as the original leukemia. Incomplete lymphoid chimerism after bone marrow transplantation might have resulted in an inappropriate graft-versus-leukemia effect.     

Allogeneic or autologous bone marrow transplantation for acute non-lymphocytic leukemia in first remission

One hundred and seven consecutive patients with acute non-lymphocytic leukemia (ANL) aged less than 56 years were allocated to receive either allogeneic (allo-BMT) or autologous bone marrow transplantation (auto-BMT) when first complete remission (CR1) was achieved. CR was obtained in 96 patients. Twenty-four patients had an HLA-identical sibling donor and 20 of these (83%) had an allograft in CR1. Thirty-three patients (44% of the CR1 patients without donor) had an autograft in CR1. The reasons for not transplanting patients in CR1 were early relapse (nine patients), refusal (11 patients) or medical problems (23 patients). The 4-year leukemia-free survival (LFS) probability for all the CR1 patients was 25%. For the allo-BMT patients, the 4-year LFS was 71%, and for the auto-BMT patients 31% (log-rank p = 0.028). The relapse probabilities were 33% and 48% respectively (p = 0.40). If the results are analysed according to the intent of the protocol, patients with a donor had an LFS of 53%, and patients without a donor an LFS of 16% (p = 0.003). This study confirms the value of allo-BMT for consolidation of ANL in CR1. The attempt to autograft all CR1 patients without a compatible donor has not resulted in any marked improvement of LFS.     

Marrow transplantation for patients with acute lymphoblastic leukemia in first marrow remission

Forty-six patients with acute lymphoblastic leukemia (ALL) in first marrow remission underwent allogeneic marrow transplantation between August 1976 and June 1985. Thirty-four patients had no extramedullary disease after remission induction and 12 had extramedullary relapses prior to or at the time of marrow grafting. The conditioning regimen included cyclophosphamide followed by total body irradiation, 9.2-15.75 Gy, administered as a single dose or in six or seven daily fractions. Marrow donors were genotypically HLA-identical siblings. Methotrexate was given as prophylaxis for graft-versus-host disease (GVHD). Forty-four patients had marrow engraftment. The incidence of grades II-IV acute GVHD was 52%. Clinical chronic GVHD occurred in 21 patients. Eighteen patients are alive 1-9 years (median = 4.2 years) after marrow grafting, 15 of whom are in continuous complete remission. The estimated probability of relapse within 2 years (+/- standard error) is 41 +/- 9% and the probability of relapse-free survival at 5 years is 28 +/- 7%. Major causes of death were recurrent leukemia, acute GVHD and interstitial pneumonia. Actuarial probabilities of survival, relapse and disease-free survival were not significantly different between those patients who did and those who did not have extramedullary disease after attaining first marrow remission.     

Allogeneic bone marrow transplantation for high-risk acute lymphoblastic leukemia during first complete remission

Fifty-three patients with high-risk acute lymphoblastic leukemia (ALL) under age 50 with a histocompatible sibling donor received high-dose radiochemotherapy followed by allogeneic bone marrow transplantation (BMT). The high-risk factors used to identify the patients were: white blood cell count at initial presentation, cytogenetic abnormalities, age, extramedullary leukemic infiltration, and time from initial therapy to complete remission. Patients with one or more of the above risk factors who received BMT have a disease-free survival of 61% with a median follow-up of 66 months (range 11 months to 10.6 years), and an actuarial relapse rate of 10%. This study demonstrates that patients with high-risk ALL achieve a significant disease-free survival and cure rate with the use of allogeneic fully matched sibling BMT. However, a properly designed prospective study comparing the outcome of BMT with the best currently available chemotherapy data is required to define the ultimate role of BMT in this group of patients.     

Autologous marrow transplantation in patients with acute nonlymphocytic leukemia in first remission

Thirteen patients with acute nonlymphocytic leukemia underwent autologous bone marrow transplantation (ABMT) following high doses of cyclophosphamide and total body irradiation while in first complete remission. After marrow infusion four patients received human leukocyte interferon and nine received intravenous methotrexate. One patient died on day 16 of septicemia associated with severe gastrointestinal toxicity. In the remaining 12 patients the median day of achieving a circulating granulocyte level of 500/mm3 was 29 (range 15-94 days). Eight of 12 evaluable patients achieved a sustained platelet count of 20,000/mm3 or greater in a median of 44 days (range 12-116 days) and four patients did not achieve this level before death on days 116-396. One patient died on day 116 of interstitial pneumonitis secondary to cytomegalovirus. Eight patients relapsed 58-365 days after AMBT (median 335 days), and all have died. Three patients are alive and well without relapse 26-50 months after ABMT. This study demonstrated that poor engraftment was a frequent complication of ABMT when early posttransplant cytotoxic therapy was attempted. Relapse of leukemia and the number of long-term survivors in this small group of patients was not different from that expected following conventional therapy.     

Allogeneic or autologous bone marrow transplantation for acute lymphoblastic leukemia in first complete remission

Forty-seven patients with high risk acute lymphoblastic leukemia (ALL) received an allogeneic (allo) or autologous (auto) bone marrow transplant (BMT). Patients in both groups were comparable in terms of age, initial presentation of ALL and induction chemotherapy. Allo patients were transplanted earlier (median 3 months after CR) than auto patients (median 6.5 months after CR). Auto patients received more consolidation chemotherapy before BMT. All patients received total body irradiation 2.2 Gy/day x 5 days after cyclophosphamide 60 mg/kg x 2 (18 allo and five auto) or melphalan 140 mg/m2 (seven allo and 17 auto). Prevention of graft-versus-host disease (GVHD) was by conventional immunosuppression in 17 patients and T cell depletion in eight. Seven patients (28%) developed moderate to severe acute GVHD. Auto marrow was treated in vitro in each case. Seven patients died in CR from BMT complications (five allo and two auto). The probability of relapse was 9% for patients receiving allo BMT and 52% for patients receiving auto BMT (p less than 0.01). The disease-free survival was 71% for allo BMT and 40% for auto BMT (p = NS). Early BMT is an effective form of consolidation for high risk patients with ALL in first CR. An allogeneic anti-leukemia effect was demonstrated in this study.     

T-cell-depleted allogeneic bone marrow transplantation in adults with acute nonlymphocytic leukemia in first remission.

We prospectively evaluated the efficacy of T-cell-depleted bone marrow transplantation (BMT) in adults with de novo acute nonlymphocytic leukemia (ANLL) in first complete remission (CR), with regard to relapse-free survival and incidence of graft-versus-host disease (GvHD). Thirty-one patients older than 16 years (range, 16.5 to 43.2) received T-cell-depleted grafts for this purpose from related HLA/MLC-compatible donors. Twelve of the patients were older than 30 years at the time of transplantation. Patients were prepared with hyperfractionated total body irradiation (HFTBI; 1,375 to 1,500 cGy) and high-dose cyclophosphamide (120 mg/kg). T cells were removed from the marrow grafts by a two-step soybean lectin agglutination and sheep red blood cell (sRBC)-rosette procedure, achieving a 2.5- to 3-log depletion of clonable T lymphocytes. No additional prophylaxis against GvHD was administered. The median age at transplantation was 28.8 years; the median interval from diagnosis to transplantation was 3.8 months, and from CR was 2.7 months. Seventy-four percent received consolidation after remission induction therapy. The product-limit estimate of disease-free survival (DFS) at 3 years is 45% (95% confidence interval [CI], 24% to 66%), and the cause-specific probability of relapse is 13%. The median follow-up of the survivors is 72 months (range, 34.5 to 95.6). Median time to achieve a sustained absolute neutrophil count of 500 or greater was 16 days, and to maintain an untransfused platelet count of 20,000 or greater was 20 days. Five patients suffered immune-mediated graft rejection. Three patients developed grade I to II acute GvHD limited to the skin, which resolved promptly with brief courses of systemic steroids. None of the patients has developed clinically apparent chronic GvHD or a secondary lymphoproliferative disorder, and no patient is receiving immunosuppressive therapy. T-cell-depleted BMT by the method reported here is a favorable option as postremission therapy for adults with de novo ANLL in first remission who have an HLA/MLC-compatible related donor, and it is not associated with an increased risk of relapse posttransplant.     

Autologous and allogeneic bone marrow transplantation in acute myeloid leukemia in first complete remission: an update of the Genoa experience with 159 patients

Summary In the attempt to evaluate the role of Autologous and Allogeneic Bone Marrow Transplantation, we have retrospectively analyzed 159 patients with Acute Myeloid Leukemia in first complete remission treated in our Unit, most of whom were referred from other Institutions. High-dose therapy was uniform and consisted of cyclophosphamide 60 mg/kg/d on two consecutive days and TBI in a single dose (10 Gy) for ABMT patients and in fractionated doses (3.3 Gy × 3 days) for BMT patients. Eight years actuarial survival was similar in two groups (52% for BMT and 49% for ABMT). The actuarial risk of relapse for BMT and ABMT was 29% and 43%, respectively. Considering that none of ABMT patients was purged with in vitro technique, this review seems to confirm the importance of in vivo purging with postremission intensification, immediately before the harvesting. Of course, more patients and a longer follow-up are needed to drow final conclusions.     

Bone marrow ablation followed by allogeneic marrow grafting during first complete remission of acute nonlymphocytic leukemia

Of 33 patients who had undergone allogeneic bone marrow transplantation during first complete remission of acute nonlymphocytic leukemia, 21 patients have now been followed in continued complete remission for 6- 64 mo (median greater than 18 mo) without maintenance chemotherapy. The median age of the surviving patients is 27 yr. Transplant-related complications occurring throughout the first year after marrow grafting were fatal in 7 patients, and leukemic recurrence led to the death of 5 patients. The actuarial long-term disease-free survival is 60% and the actuarial remission rate is 79%.     

Allogeneic bone marrow transplantation for acute nonlymphocytic leukemia in first remission

Seventy-three patients with acute nonlymphocytic leukemia in first complete remission (CR) have received allogeneic bone marrow transplantation (BMT) with non-T-lymphocyte-depleted marrow obtained from matched sibling donors. The first 36 patients received a preparative regimen consisting of cyclophosphamide, 60 mg/kg/d (days -6 and -5), and 750 cGy single-dose total-body irradiation (TBI) (day -1). Subsequently, 37 patients received cyclophosphamide 60 mg/kg/d (days -6 and -5), and 165 cGy fractionated TBI administered twice daily for a total dose of 1,320 cGy (days -4, -3, -2, and -1). Survivors have been followed from 9 to 124 months (median, 40 months). The 61% (95% confidence interval [CI], 45% to 77%) projected disease-free survival (DFS) of 41 children less than 18 years old does not differ significantly from the 62% (95% CI, 49% to 73%) projected DFS of 32 adults at 84 months (P = .89). Similarly, the 15% (95% CI, 1% to 29%) projected relapse rate seen in children does not differ from the 9% (95% CI, 0% to 21%) seen in adults (P = .69). Multivariate Cox regression analysis of presenting features demonstrates that a presenting WBC count greater than 20,000/m3 is associated with decreased DFS (P = .01). When compared with other French-American- British (FAB) subtypes, presentation with FAB M4 or M5 morphology is significantly associated with relapse in multivariate analysis (P = .014). Other presenting features such as preparation with single-dose or fractionated TBI, interval from diagnosis to CR or CR to BMT, donor or recipient sex, and donor or recipient cytomegalovirus serology do not correlate independently with either DFS or relapse. When included in the stepwise multivariate analysis of presenting patient features, two posttransplant events, development of grades 2 to 4 acute graft-v- host disease (GVHD) (P less than .03) and development of interstitial pneumonitis (P less than .001), also correlate independently with poor DFS. Allogeneic BMT provides equivalent, prolonged DFS in both children and young adults when performed in first CR and should be considered the therapy of choice for all first CR patients under 45 years of age with a suitable donor. Continued efforts to prevent and treat acute GVHD and pneumonitis as well as efforts designed to prevent relapse in patients presenting with FAB M4 and M5 morphology should further improve outcome.     

Transient complete remission of acute lymphoblastic leukemia in relapse after allogeneic bone marrow transplantation induced by donor leukocyte transfusions

We report the case of a young patient with refractory acute lymphoblastic leukemia relapse, after allogeneic bone marrow transplantation, who was treated by donor leukocyte infusions. We observed potent adoptive immunotherapy which produced a cytologic complete remission and total chimeric state. This was of short duration and the patient died of severe graft-versus-host disease. We present a short summary of the literature concerning acute lymphoblastic leukemia and donor leukocyte infusions.     

Transient complete remission of acute lymphoblastic leukemia in relapse after allogeneic bone marrow transplantation induced by donor leukocyte transfusions

We report the case of a young patient with refractory acute lymphoblastic leukemia relapse, after allogeneic bone marrow transplantation, who was treated by donor leukocyte infusions. We observed potent adoptive immunotherapy which produced a cytologic complete remission and total chimeric state. This was of short duration and the patient died of severe graft-versus-host disease. We present a short summary of the literature concerning acute lymphoblastic leukemia and donor leukocyte infusions.     

Allogenic bone marrow transplantation of chemotherapy for patients with acute myeloid leukemia in first complete remission: a decision analysis approach

 The methodology of decision analysis was originally developed to improve clinical decisions of physicians for individual patients. However, it is also well suited to support consensus procedures. We have used this methodology to analyse the question whether allogeneic bone marrow transplantation (BMT) or consolidation chemotherapy (CCT) should be used as first line postremission treatment in patients with acute myeloid leukemia. Main risk factors relevant for the outcome after BMT and CCT are therapy-related mortality and leukemic relapse, respectively. If the possibility of salvage BMT for patients relapsing after CCT is included, the outcomes of the two strategies come rather close. However, they are clearly different in subtypes of leukemia with high or low risk of relapse, and in patients at high risk for BMT-related mortality. Sensitivity analysis considering the variation of more than one risk factor provides valuable information for decision making for both individual patients and particular subgroups of patients with acute myeloid leukemia. Received: 22 January 1996 / Accepted: 25 January 1996     

Long-term complete remission after allogeneic bone marrow transplantation in multiple myeloma.

We report a case of IgG lambda type multiple myeloma treated by allogeneic bone marrow transplantation. After transplant the monoclonal protein persisted for 2 years with no other sign of disease. Thereafter the monoclonal protein was no longer detectable and the patient was considered to be in complete remission for the next 4 years.