Remission Reinduction Research Articles

抗CD20モノクローナル抗体(rituximab)療法後，短期間にCD20陰性の多発性皮膚腫瘤で再発したびまん性大細胞型B細胞リンパ腫

A 60-year-old male was referred to our hospital because of cervical lymphadenopathy and a left hilar abnormal shadow seen on chest X-ray in May 1999. The pathological findings of the cervical lymph nodes revealed that the patient had a malignant lymphoma, of the diffuse large B cell type, at clinical stage IIIB. Immunohistochemistry demonstrated that the lymphoma cells were positive for CD11a, CD19, CD20, CD23, CD25, CD45, IgM, IgD and lambda, but negative for CD5. Although a complete remission was obtained after 8 courses of CHOP therapy, the patient relapsed 32 months later. Two courses of a half dose of CHASE therapy consisting of CPM, ara-C, VP-16 and dexamethasone, followed by rituximab (600 mg/week x4) resulted in a transient re-induction of complete remission. However, multiple cutaneous tumors became apparent just 10 days after the last rituximab therapy. Immunohistochemistry of the cutaneous tumors revealed infiltration of CD20-negative lymphoma cells. A series of chemotherapy including high-dose MTX was ineffective, and the patient died in August 2003. Autopsy findings revealed the systemic intra-capillary infiltration of CD20 negative-lymphoma cells into multiple organs, including the lungs, liver, and kidneys. A CD20 negative-clone selected by rituximab therapy appeared to have expanded in this case.

Donor leukocyte infusions for the treatment of relapsed acute leukemia after allogeneic stem cell transplantation

Allogeneic stem cell transplantation (SCT) offers the only hope for cure for many adults with acute leukemia. Unfortunately, many patients relapse and die of their disease even after transplantation. Although in some cases, allogeneic SCT is effective because the intensive conditioning therapy eradicates all malignant cells, it has long been recognized that the adoptive transfer of donor immunity plays a critically important role in the induction and maintenance of remission. Recognition of the graft-versus-leukemia (GVL) effect of allogeneic SCT has prompted attempts at remission re-induction by adoptive immunotherapy with donor lymphocyte infusions (DLIs) in patients with relapsed disease after allogeneic SCT. In some cases, DLI-induced remissions are sustained and patients cured when no other treatment modality was effective. This review discusses the rationale, biology, complications and future applications of DLI in acute leukemia patients after allogeneic SCT.

Successful Reinduction of Remission by DLI for Relapsing Infant AML after Reduced-Intensity Hematopoietic Stem Cell Transplantation

Successful Reinduction of Remission by DLI for Relapsing Infant AML after Reduced-Intensity Hematopoietic Stem Cell Transplantation

Fludarabine, Idarubicin and High Dose Cytarabine (FLAG-IDA) Followed by Allogeneic Transplantation: A Successful Strategy for Remission Re-Induction in High Risk Pediatric Patients with Relapsed, Refractory and Secondary Acute Leukemias.

Despite significant advances in the treatment of childhood acute lymphoblastic (ALL) and acute myeloid (AML) leukemias, the prognosis of those with primary refractory, secondary and early relapsed disease remains extremely poor with survival reported in most studies at less than 20%. Salvage rates are particularly poor in children with ALL who relapse on therapy and in children with AML who relapse post autologous bone marrow transplant. Encouraging results using the re-induction combination regimen of Fludarabine, high dose Cytarabine and Idarubicin (FLAG-IDA) have been reported, however the majority of data is in adult patients. Here we report the largest series of pediatric patients with high risk acute leukemias receiving this regimen in combination with allogeneic hematopoietic cell transplantation as salvage therapy.Between 1999–2005 a toal of 32 patients at 2 Australian Pediatric Cancer Centers were given Fludarabine (30mg/m2 IV over 1 hour for 5 days); Idarubicin (8mg/m2 IV over 1 hour for 3 days); Cytarabine (2000mg/m2 IV over 4 hours for 5 days) and GCSF (5mcg/kg/day). There were 21 males and 11 females, with a median age of 10.4 years (range 1.7 to 15.5 years). All patients had high risk leukemias; relapsed ALL (n=13), primary refractory ALL (n=3), relapsed AML (n=13), primary refractory AML (n=1) and secondary AML (n=2). For the overall cohort median duration of first complete remission (CR1) was 16 months (range 2–34 months). Relapsed ALL patients were all considered extremely high risk with a CR1 duration of <36 months.Overall, 23 of 32 patients (71.9%) achieved a complete remission (defined as <5% blasts with evidence of marrow regeneration) following a single course of FLAG-IDA. For those with relapsed ALL, 10 of 13 patients (76.9%) achieved a remission. 2 out of the 3 patients with primary refractory ALL achieved a remission (both Philadelphia chromosome positive), 1 following a second course of FLAG-IDA. In the relapsed AML group, 9/13 (69.2%) achieved a remission, including 7 out of 10 patients who had relapsed post autologous BMT. 1 of the 2 patients with secondary AML achieved a remission. All of the 9 patients who did not achieve a remission died of progressive disease. The median time to neutrophil recovery following therapy was 26.5days (range 16–73). One patient remained aplastic and an attempt was made to transplant during this phase.22 of the 23 patients (10 AML and 12 ALL) who achieved remission proceeded to an allogeneic bone marrow transplant, following a further 2–3 courses of FLAG (without IDA) for consolidation. 70% of patients received an unrelated donor transplant. Stem cell source was MUD BM (n=9), unrelated UCB (n=6) and HLA-ID sibling donor (n=7). Overall 17 of the 22 (77.3%) remain alive and leukaemia free (9 AML and 8 ALL patients) with a median duration of 36.5 months (9–84 months). Cause of death in the transplanted patients was progressive disease (n=4) and Pneumocystis Carinii pneumonitis (n=1). In summary, for this group of high risk, early relapsed and heavily pretreated pediatiric patients, re-induction chemotherapy with FLAG-IDA followed by allogeneic transplantation has provided an excellent strategy in the achievement of long term cure.

Dexamethasone, Melphalan, Actinomycin D, Cytosine Arabinoside (DMAC) Protocol for Dogs with Relapsed Lymphoma

Background:In general, treatment of relapsed lymphoma is associated with a lower probability of response and shorter duration of remission. The purpose of this study was to evaluate the efficacy of the combination chemotherapy protocol DMAC (dexamethasone, melphalan, actinomycin D, and cytosine arabinoside) for reinduction of remission in dogs with relapsed lymphoma.Hypothesis:That DMAC would be an effective reinduction protocol for dogs with relapsed lymphoma.Animals:Fifty‐four dogs.Results: Seventy‐two percent of the dogs achieved remission (44% complete remission [CR] and 28% partial remission [PR]), 11% had stable disease (SD), and 17% had progressive disease (PD). The median remission duration was 61 days (range, 2–467+ days). The median remission durations for dogs with CR, PR, and SD were 112, 44, and 27 days, respectively. Factors that affected the response rate were previous treatment with doxorubicin and an inability to achieve remission with the previous protocol. Thrombocytopenia occurred in 56% of the dogs (grade 1 in 3 dogs, grade 2 in 6 dogs, grade 3 in 7 dogs, and grade 4 in 7 dogs) and neutropenia in 17% of the dogs (grade 2 in 1 dog, grade 3 in 2 dogs, and grade 4 in 4 dogs). Gastrointestinal toxicosis occurred in 22% of the dogs (grades 1 in 5 dogs, grade 2 in 3 dogs, and grade 3 in 1 dog).Conclusions and Clinical Importance: The DMAC protocol is an effective rescue protocol for dogs with relapsed multicentric lymphoma. Although thrombocytopenia is a common manifestation of toxicity, in general, the protocol is well tolerated.

Dexamethasone, Melphalan, Actinomycin D, Cytosine Arabinoside (DMAC) Protocol for Dogs with Relapsed Lymphoma

In general, treatment of relapsed lymphoma is associated with a lower probability of response and shorter duration of remission. The purpose of this study was to evaluate the efficacy of the combination chemotherapy protocol DMAC (dexamethasone, melphalan, actinomycin D, and cytosine arabinoside) for reinduction of remission in dogs with relapsed lymphoma. That DMAC would be an effective reinduction protocol for dogs with relapsed lymphoma. Fifty-four dogs. Seventy-two percent of the dogs achieved remission (44% complete remission [CR] and 28% partial remission [PR]), 11% had stable disease (SD), and 17% had progressive disease (PD). The median remission duration was 61 days (range, 2-467+ days). The median remission durations for dogs with CR, PR, and SD were 112, 44, and 27 days, respectively. Factors that affected the response rate were previous treatment with doxorubicin and an inability to achieve remission with the previous protocol. Thrombocytopenia occurred in 56% of the dogs (grade 1 in 3 dogs, grade 2 in 6 dogs, grade 3 in 7 dogs, and grade 4 in 7 dogs) and neutropenia in 17% of the dogs (grade 2 in 1 dog, grade 3 in 2 dogs, and grade 4 in 4 dogs). Gastrointestinal toxicosis occurred in 22% of the dogs (grades 1 in 5 dogs, grade 2 in 3 dogs, and grade 3 in 1 dog). The DMAC protocol is an effective rescue protocol for dogs with relapsed multicentric lymphoma. Although thrombocytopenia is a common manifestation of toxicity, in general, the protocol is well tolerated.

Allogeneic Hematopoietic Cell Transplantation (HCT) for Acute Leukemia in First Relapse or Second Remission.

Allogeneic HCT offers the best chance for long-term survival in patients with acute leukemia after first relapse. A difficult clinical decision for a patient suffering leukemic relapse who has a histocompatible donor is whether to attempt re-induction therapy or proceed directly to HCT. Sixty-five patients with acute leukemia in first relapse or second remission were treated with allogeneic HCT at 3 institutes in Seoul, Korea between Jan 1995 and Sep 2004. We analyzed their post-transplant outcomes and investigated the role of salvage chemotherapy aimed at re-induction of remission before allogeneic HCT. Forty patients received hematopoietic cell graft from a sibling donor, 21 from an unrelated donor, and 2 from a haplo-identical family donor, and 2 received cord blood. Thirteen patients received TBI-based conditioning regimen and 10 received reduced-intensity conditioning regimen. There occurred 34 relapses with 51.3% of 5-y cumulative incidence of relapse (CIR) and there were 22 non-relapse deaths with 34.7% of non-relapse mortality. Probabilities of overall survival and disease-free survival were 20.6% and 14.0% at 5-y, respectively. Multivariate analysis by Gray method for CIR revealed that patients with unfavorable cytogenetics (Philadelphia chromosome-positive or complex karyotype) and those not in remission at the time of HCT had significantly higher CIR (P=0.023 and P=0.031, respectively). Fourteen patients underwent allogeneic HCT after first relapse without salvage chemotherapy aimed at re-induction of remission (“untreated relapse”), 15 patients failed in attempts aimed at re-induction of remission before HCT (“refractory relapse”), and 36 patients attained second remission with salvage chemotherapy before HCT (“second remission”). 5-y CIR for “untreated relapse” (57.1%) was higher than that for “second remission” (42.3%), but lower than that for “refractory relapse” (66.7%). Among patients transplanted in relapse, those with BM blasts ≤ 30% seemed to have lower 5-y CIR than patients in florid relapse (BM blasts > 30%) (57.7% vs. 70.6%). These results do not support the role of salvage chemotherapy aimed at re-induction of remission before allogeneic HCT in patients with acute leukemia after first relapse. At least the patients with early relapse do not appear to receive benefit from salvage chemotherapy before HCT.

Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia after first relapse

Using flow cytometric techniques capable of detecting 0.01% leukemic cells, we prospectively studied minimal residual disease (MRD) in patients with acute lymphoblastic leukemia (ALL) after first relapse. At the end of remission reinduction, 41 patients had a bone marrow sample adequate for MRD studies; 35 of these were in morphologic remission. Of the 35 patients, 19 (54%) had MRD >/=0.01%, a finding that was associated with subsequent leukemia relapse. The 2-year cumulative incidence of second leukemia relapse was 70.2+/-12.3% for the 19 MRD-positive patients and 27.9+/-12.4% for the 16 MRD-negative patients (P=0.008). Among patients with a first relapse off therapy, 2-year second relapse rates were 49.1+/-17.8% in the 12 MRD-positive and 0% in the 11 MRD-negative patients (P=0.014); among those who received only chemotherapy after first relapse, the 2-year second relapse rates were 81.5+/-14.4% (n=12) and 25.0+/-13.1% (n=13), respectively (P=0.004). Time of first relapse and MRD were the only two significant predictors of outcome in a multivariate analysis. We conclude that MRD assays should be used to guide the selection of postremission therapy in patients with ALL in first relapse.

Treatment of hemophagocytic lymphohistiocytosis, HLH, with bone marrow transplantation

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease of infancy and young childhood. The clinical presentation includes recurrent unexplained fever with hepatosplenomegaly. Cytopenia, hypofibrinogenemia and/or hypertriglyceridemia and hemophagocytosis in bone marrow, spleen and lymphnode confirm the diagnosis. Hemophagocytosis may not be present at the beginning. In these cases, diagnosis is facilitated by a positive family history, a relapsing course of the disease, the frequent involvement of the central nervous system and positive findings on immunological work-up. Treatment by chemotherapy and immunosuppressants can achieve sustained remissions in most patients and reinduction of remission after relapse is possible. Most children however, eventually die from progressive disease. At present, allogeneic bone marrow transplantation is the only curative therapeutic option. Between August 1992 and May 1997 eleven consecutive patients with HLH received bone marrow from unrelated (n = 7) or matched sibling donors (n = 4). The conditioning regimen consisted of busulfan, VP-16 and cyclophosphamide. Patients engrafted after a median time of 16 days (13-43). Only one patient developed grade III acute GVHD, another patient, grade II acute GVHD. Although regimen-related toxicity was extensive, all patients have survived without signs of HLH after a median follow up of 20 months (8-63). One patient suffers from chronic GVHD, three patients reveal psychomotoric retardation and one patient has severe impairment with spastic tetraparesis, amaurosis and seizures. Our experience shows that HLH can be successfully treated by allogeneic BMT from unrelated donors.

The novel immunomodulator, Linomide, stimulates interleukin-2-induced human natural killer (NK) cell and PHA-stimulated T cell proliferation from normal donors

Donor-derived cell-mediated immunotherapy has been shown to be an effective tool for reinduction of remission in chronic myeloid leukemia (CML) patients who have relapsed post-bone marrow transplantation (BMT). Linomide, quinoline-3-carboxamine (LS 2616), is a new immunomodulator shown to increase the number of NK precursors in mice in addition to upregulating the quantity of CD56 +, CD3 − and CD16 + NK cells in the peripheral blood of patients following autologous BMT (ABMT). We investigated the in vitro effects of Linomide on NK activity of normal human donors. Large granular lymphocytes (LGLs) and NK cells were incubated overnight with Linomide (0.02–4.8 mg/ml), recombinant human interleukin-2 (IL-2, 75 IU/ml), or a combination of both. Linomide, at 0.02–0.3 mg/ml, augmented IL-2-induced proliferation of LGLs and NK cells in an inversely proportional manner. In contrast, Linomide at 0.6–4.8 mg/ml inhibited IL-2-induced proliferation of LGLs and NK cells in a dose-dependent manner. Linomide was able to potentiate phytohemaglutinin-induced CD3 + T cell proliferation. In addition, supernatants derived from Linomide treated CD3 + T cells were able to mimic the direct stimulatory effect of Linomide on activated NK cell proliferation. These supernatants were found to have low levels of tissue necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) and therefore Linomide stimulation of NK and T cell proliferation may be due to its inhibitory effect on the secretion of these cytokines by activated CD3 + T cells. Linomide had no effect on cytotoxicity nor on the phenotypic expression of resting and IL-2-activated LGLs or NK cells. In view of our results, Linomide could possibly play a potential role in adoptive cell-mediated immunotherapy post-BMT.

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-alpha, 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.

An effective salvage regimen with aclarubicin for daunorubicin-resistant acute non-lymphocytic leukemia in children.

We evaluated the efficacy and toxicity of aclarubicin for acute non-lymphocytic leukemia (ANLL) refractory to daunorubicin in childhood. Twenty-four patients were treated with aclarubicin and prednisolone with or without 6-mercaptopurine and behenoyl-cytosine arabinoside daily for 5 to 14 days. Of 21 evaluable patients, 14 (67%) responded: 12 obtained complete remission and 2 partial remission. The median time to reach complete remission was 37 days (range, 16 to 60 days), and the median duration of complete remission was 5.5 months (range, 2 to 41 months). The cumulative dose of anthracycline administered before the study was not considered significant for the response. The only major complication was severe bone marrow suppression; infectious episodes occurred in 14 patients (58%) and three died of sepsis and/or bleeding. The observed non-hematologic toxicities included hematuria, an elevation of serum amylase, nausea/vomiting, and angitis. In addition, one patient showed abnormal cardiac function. Aclarubicin is therefore considered a highly active drug for remission reinduction of previously treated children suffering from ANLL with an acceptable toxicity.

Actinomycin D for reinduction of remission in dogs with resistant lymphoma.

Twenty-five dogs with malignant lymphoma refractory to chemotherapy were treated with actinomycin D at a median dose of 0.7 mg/m2 (range, 0.5 to 0.9 mg/m2) every 3 weeks. The dogs treated had received between 2 and 8 chemotherapeutic agents (median 7), for a median of 266 days before being treated with actinomycin D. For 23 of the 25 dogs, previous chemotherapy included doxorubicin. No dog responded to actinomycin D chemotherapy.

Nonhereditary p53 Mutations in T-Cell Acute Lymphoblastic Leukemia Are Associated With the Relapse Phase

AbstractWe have previously reported that greater than 60% of human leukemic T-cell lines possess mutations in the p53 tumor suppressor gene. To determine whether T-cell acute lymphoblastic leukemia (T-ALL) patient samples possess p53 mutations, we screened peripheral blood- and bone marrow-derived leukemia samples, taken at diagnosis and at relapse, for p53 mutations. Exons 4 through 9 and selected intron regions of the p53 gene were analyzed using polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. p53 mutations were found in 0 of 15 T-ALL diagnosis samples, as compared with 10 of 36 (28%) T-ALL relapse samples. To determine whether p53 mutations play a role in the recurrence (relapse) of T-ALL, two special groups of T-ALL patients were studied: (1) a group of 8 relapse patients whose disease was refractory to chemotherapeutic treatment, and (2) a group of 6 “paired” T-ALL cell samples from patients for whom we possess both diagnosis and relapse samples. Three of 8 relapsed patients (37.5%) whose disease was refractory to the reinduction of remission by chemotherapy possessed missense mutations of the p53 gene. All 3 cases had mutations in exon 5. Among the paired samples, 3 of 6 patients harbored p53 mutations at disease recurrence, but possessed only wild-type p53 alleles at diagnosis. One case had mutation on exon 4, 1 case in exon 5, and 1 case in exon 8 with loss of heterozygosity. These data clearly indicate that recurrence of T-ALL is associated with missense mutations in p53. Our results indicate that (1) mutations of p53 do occur in T-ALL in vivo, and such mutations are associated with the relapse phase of the disease; and (2) p53 mutation is involved in the progression of T-ALL. This conclusion is supported by our observation that the introduction of T-ALL-derived mutant p53 expression constructs into T-ALL cell lines further increases their growth rate in culture, enhances cell cloning in methylcellu-lose, and increases tumor formation in nude mice.

Treatment of late bone marrow relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study

Children with acute lymphoblastic leukemia (ALL) who have completed 2.5 to 3 years of initial chemotherapy have an off-therapy relapse rate of approximately 20%. In an attempt to improve the survival of children with a late bone marrow (BM) relapse (ie, occurring greater than 6 months after cessation of primary therapy), the Pediatric Oncology Group designed a randomized study to compare the efficacy of doxorubicin/prednisone and cytarabine/teniposide in a multidrug retreatment chemotherapy program. Treatment consisted of remission reinduction with vincristine, prednisone, and doxorubicin, central nervous system prophylaxis with triple intrathecal chemotherapy, and continuation therapy (for 132 weeks) with alternating cycles of oral 6-mercaptopurine/methotrexate and intravenous vincristine/cyclophosphamide. Patients received intermittent courses of either prednisone/doxorubicin (regimen 1) or teniposide/cytarabine (regimen 2) during continuation therapy and a late intensification phase with either vincristine, prednisone, and doxorubicin (regimen 1) or teniposide and cytarabine (regimen 2). One hundred two of 105 evaluable patients (97%) achieved a second complete remission. Twenty-eight of 50 patients on regimen 1 have failed compared with 28 or 52 patients on regimen 2 (log-rank analysis, P = .68), indicating that this trial was inconclusive as to which treatment regimen was superior. The overall 4-year event-free survival for children with a late BM relapse was 37% +/- 6%. Age less than 10 years at initial diagnosis (P < or = .001), white blood cell count less than 5,000/microL at relapse (P = .036) and duration of first remission greater than 54 months (P = .039) were independently associated with a more favorable outcome. While the randomized trial was inconclusive, prolonged second complete remissions were secured in more than one-third of children with a late BM relapse of ALL. The prognostic factors identified may help select children with a late BM relapse who can be successfully retreated with chemotherapy alone.

Successful Reinduction of Complete Remission in a Patient with ALL Associated with Multiple Liver Abscesses who Relapsed after 6 Years

Successful Reinduction of Complete Remission in a Patient with ALL Associated with Multiple Liver Abscesses who Relapsed after 6 Years

Cyclic combination chemotherapy for acute lymphoblastic leukemia recurring after elective cessation of therapy.

Cyclic combination chemotherapy was administered to 26 patients with acute lymphoblastic leukemia who had relapsed in the bone marrow greater than or equal to 6 months after elective cessation of therapy. Each patient had been in initial continuous complete remission for 36-111 months (median, 47 months). Prednisone, vincristine, and doxorubicin induced second complete remissions in all patients within 1 month. Continuation therapy consisted of alternating 6-week courses of 6-mercaptopurine/methotrexate and vincristine/cyclophosphamide with intervening reinforcement courses of prednisone/doxorubicin, for a total of 18 months. All patients received 4 weeks of late intensification therapy with the same agents used for remission reinduction. Periodic intrathecal methotrexate was given as reprophylaxis for subclinical central nervous system leukemia. The estimated rate of continuous failure-free survival at 5 years is 31% +/- 17% (2 SE). Eight patients remain free of leukemia for 42 + to 65+ months after completing therapy a second time. Adverse second events included 11 hematologic, 1 testicular, and 3 meningeal relapses. Patients who relapsed at more than 12 months after the completion of initial treatment have had significantly longer second remissions than patients whose first remissions were shorter (p = .04). None of the other six factors we analyzed showed predictive strength. These end results indicate that intensive cyclic continuation chemotherapy, as described here, will secure durable second remissions in approximately one-third of the children with late bone marrow relapses.

How zealously should a patient with relapsed acute myeloid leukaemia be treated?

A relapse of acute myeloid leukaemia occurred in a 45-year-old woman 18 months after the disease was initially diagnosed and treated. During remission reinduction therapy, she developed a Gram-negative septicaemia, acute respiratory failure, acute renal failure, diabetic hyperglycaemia with ketoacidosis, and probable bacterial meningitis. She required assisted respiration for two days, received peritoneal dialysis for five days, and was unconscious for seven days. The patient eventually recovered, achieved full remission of her leukaemia, and survived a further 2 1/2 years, mostly in excellent health. Oncologists are often criticized for unjustifiable optimism and excessive zeal in the treatment of patients with malignant disease. This case illustrates that such optimism and zeal may be justified, and that intensive efforts to save the lives of seriously ill patients with chemosensitive malignant diseases are worthwhile.

Allogeneic Marrow Transplantation for Acute Nonlymphoblastic Leukemia After First Relapse

Sixty-two patients with acute nonlymphoblastic leukemia in first relapse or second remission were treated with allogeneic marrow transplantation from HLA-matched siblings. In 17 patients (group 1), no attempt at reinduction of remission was made prior to transplantation. In 20 patients (group 2), attempts at inducing a second remission prior to transplantation were unsuccessful; and in 25 patients (group 3), a second remission was achieved. Five of 17 patients (29%) in group 1, 2 of 20 (10%) in group 2, and 5 of 25 (20%) in group 3 are surviving disease-free 2-6 yr after grafting. Early mortality from nonleukemic causes was equal in the 3 groups, but the risk of recurrent leukemia after transplantation was less in patients transplanted without attempts at reinduction (group 1). Among patients transplanted in relapse, those in early relapse (less than 30% blast cells in the marrow) appeared to do better than patients in florid relapse. The results obtained in group 1 are as good as or better than those achieved in patients transplanted in second or subsequent remission. Thus, for patients with acute nonlymphoblastic leukemia not transplanted in first remission, the optimal time for transplantation would appear to be as soon as possible after the first relapse.

Allogeneic marrow transplantation for acute nonlymphoblastic leukemia after first relapse

Sixty-two patients with acute nonlymphoblastic leukemia in first relapse or second remission were treated with allogeneic marrow transplantation from HLA-matched siblings. In 17 patients (group 1), no attempt at reinduction of remission was made prior to transplantation. In 20 patients (group 2), attempts at inducing a second remission prior to transplantation were unsuccessful; and in 25 patients (group 3), a second remission was achieved. Five of 17 patients (29%) in group 1, 2 of 20 (10%) in group 2, and 5 of 25 (20%) in group 3 are surviving disease-free 2–6 yr after grafting. Early mortality from nonleukemic causes was equal in the 3 groups, but the risk of recurrent leukemia after transplantation was less in patients transplanted without attempts at reinduction (group 1). Among patients transplanted in relapse, those in early relapse (less than 30% blast cells in the marrow) appeared to do better than patients in florid relapse. The results obtained in group 1 are as good as or better than those achieved in patients transplanted in second or subsequent remission. Thus, for patients with acute nonlymphoblastic leukemia not transplanted in first remission, the optimal time for transplantation would appear to be as soon as possible after the first relapse.