Relapse Of Lymphoblastic Leukemia Research Articles

Case report: atypical, unilateral optic nerve infiltration as the first sign of acute lymphoblastic leukemia (ALL) relapse

BackgroundWe describe a case of an atypical presentation of leukemic optic nerve infiltration.Case presentationA patient with acute lymphoblastic leukemia (ALL) in remission suffered from sudden right eye vision loss. At the time of presentation, the affected eye presented with an afferent pupillary defect, while the fundus examination was normal. A complete work up of the patient revealed no signs of ALL relapse, but MR imaging of the optic nerve showed contrast agent uptake consistent with optic nerve infiltration. The patient developed a fulminant ALL relapse and died shortly after. Histology of the optic nerve showed a leukemic infiltration with CD10 positive cells.ConclusionsThis is the first report of an ALL relapse in the optic nerve without intraocular signs. Patients’ medical history should therefore be taken into consideration in patients with unclear vision loss.

ALL-052: New Therapeutics in Cancer Treatment: Analysis of Socioeconomic and Demographic Characteristics of Use Among Acute Lymphoblastic Leukemia (ALL) Patients in the United States

Objective: Evaluate the socioeconomic dynamics associated with new therapeutics use among acute lymphocytic leukemia (ALL) patients in the United States. Design: This retrospective study included the primary and secondary diagnosis of acute lymphocytic leukemia (ALL) in the National Inpatient Sample (NIS) from the Healthcare Cost and Utilization Project (HCUP) between 2016 and 2018. ALL and new treatment therapeutics, diagnoses, and procedure codes were identified using their corresponding International Classification of Disease (ICD-10) codes. ALL ICD-10 codes were acute lymphoblastic leukemia not having achieved remission (C91.00), acute lymphoblastic leukemia in remission (C91.01), acute lymphoblastic leukemia in relapse (C91.02), and new technologies codes for anatomical regions (XW0, XW1, XW2). Patient characteristics and demographics data were analyzed among the population with both indicators. Chi-squared analysis was also conducted to identify relationships between variables. Results: A weighted sample of 158,090 primary and secondary ALL diagnoses were identified. A total of 2,320 (1%) records with ALL diagnoses were treated with new therapeutics. The most common new therapies included administration of blinatumomab antineoplastic immunotherapy (1.9%), cytarabine and daunorubicin liposome (0.3%), and engineered autologous chimeric antigen receptor T-cell immunotherapy (0.2%). The utilization rate of engineered chimeric antigen varied by sex, with 6,250 males and 3,750 females per 10,000 hospitalizations. Use of new therapeutics varied significantly (p Conclusions: Access to new therapeutics varied by race, income, and region. Therefore, providers and researchers must ensure comprehensive inclusion of all patient populations to better understand new drug effectiveness among these populations.

Successful treatment of acute B lymphoblastic leukemia relapse in the skin and testicle by anti-CD19 CAR-T with IL-6 knocking down: a case report

BackgroundExtramedullary relapse is an important cause of treatment failure among patients with acute lymphoblastic leukemia (ALL). This type of relapse is commonly observed in the central nervous system, while it is rare in the testicles and skin. Chimeric antigen receptor-modified T cell (CAR-T) therapy targeting CD19 has shown to be a beneficial treatment approach for relapsed/refractory B cell acute lymphoblasticleukemia (r/r B-ALL). Yet, few studies have reported data regarding the treatment of extramedullary B-ALL relapse, especially both in skin and testicle, with CAR-T therapy.Case presentationHere we reported a single case of a patient with relapsed B-ALL in skin and testicle who was successfully treated by the shRNA-IL6-modified anti-CD19 CAR-T(ssCAR-T-19) therapy. A 29-year-old man with relapsed B-ALL in skin and testicle was enrolled in clinal trial involving the shRNA-IL6-modified anti-CD19 CAR-T(ssCAR-T-19) therapy (ClinicalTrials.gov number, NCT03919240). The patient had toxicity consistent with the grade 1 cytokine release syndrome.ConclusionsssCART-19 therapy may be used to effectively eliminate infiltrating leukemia cells in the skin and testicle with mild toxicity, which could be a much safer approach to bridge allo-HSCT, thus further improving the patient’s outcome.Trial registrationClinicalTrials.gov number, NCT03919240, Registered 18 April 2019, retrospectively registered.

Open-label, dose-escalation, phase 1 study of venetoclax in combination with navitoclax and chemotherapy in patients with relapsed acute lymphoblastic leukemia.

TPS10575Background: Acute lymphoblastic leukemia (ALL) relapse in children and adults is associated with poor prognosis. Venetoclax (VEN) is a potent, highly selective BCL-2 inhibitor, and navitocl...

T cell exhaustion characterized by compromised MHC class I and II restricted cytotoxic activity associates with acute B lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation

Acute B lymphoblastic leukemia (B-ALL) relapse contributes predominantly to the mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the mechanism of B-ALL relapse after allo-HSCT remains unknown. The eradication of leukemia after allo-HSCT largely relies on graft-versus-leukemia (GVL) effects mediated by donor T cells. T cell exhaustion, characterized by the increased expression of inhibitory receptors and impaired function, may suppress GVL effects. In this study, we evaluated whether T cell exhaustion was involved in B-ALL relapse after allo-HSCT. The results showed that CD4+ and CD8+ T cells exhibited increased coexpression of PD-1 and Tim-3, and compromised proliferative capacity, cytokine production and cytotoxic potentials in relapsed patients. Additionally, T cells at the tumor site were more easily exhausted than T cells in the peripheral blood. Moreover, the reversal of T cell exhaustion might correlate with effective anti-leukemic responses after reinduction. These results suggested that T cell exhaustion was associated with B-ALL relapse after allo-HSCT as well as its treatment outcome.

Abstract PR02: Mechanisms of NT5C2 activating mutations driving thiopurine resistance in relapsed lymphoblastic leukemia

Abstract Activating mutations in cytosolic 5'-nucleotidase II (NT5C2) drive resistance to 6-mercaptopurine (6-MP) in relapsed acute lymphoblastic leukemia (ALL). These gain-of function alleles encode proteins with increased nucleotidase activity, yet their specific molecular mechanisms are poorly understood. Allosteric activation of NT5C2 is primarily mediated by a marked conformational change in the helix A region, which reconfigures the catalytic center for substrate access and catalysis. Here we demonstrate that constitutively active NT5C2 mutant proteins (K359Q and L375F) adopt active helix A region structures in the absence of allosteric activator. Moreover, crystallographic, structural modeling, genetic, and functional antibody analyses identify a switch-off mechanism mediated by the dynamic mobilization of Asp407 in the tip region of the arm segment which, guided by positively charged residues located in the surface of a basic inter-monomeric cavity exposed upon allosteric activation, turns off NT5C2 by interacting with and disrupting the helical conformation of helix A. Loss of this regulatory mechanism in NT5C2 mutants involving the tip region of the arm segment and the inter-monomeric cavity drives increased nucleotidase activity and allosteric response. Finally, increased allosteric activation by the Q523X mutation results from loss of the NT5C2 C-terminal acidic tail segment, which promotes a closed inactive state in basal conditions. These results uncover dynamic mechanisms responsible for NT5C2 regulation targeted by chemotherapy resistance-driving NT5C2 mutations, with important implications for the development of NT5C2 inhibitor therapies. This abstract is also being presented as Poster 05. Citation Format: Chelsea L. Dieck, Gannie Tzoneva, Farhad Forouhar, Zachary Carpenter, Marta Sanchez-Martin, Alberto Ambesi-Impiombato, Renate Kirschner-Schwabe, Scott Lew, Jayaraman Seetharaman, Liang Tong, Adolfo Ferrando. Mechanisms of NT5C2 activating mutations driving thiopurine resistance in relapsed lymphoblastic leukemia [abstract]. In: Proceedings of the Second AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; May 6-9, 2017; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(24_Suppl):Abstract nr PR02.

Abstract B62: Cell cycle alterations in paired diagnosis-relapse childhood acute lymphoblastic leukemia.

Abstract Approximately 25% of children with acute lymphoblastic leukemia (ALL) relapse. After relapse, the overall cure rate remains low, despite intensified chemotherapy and stem cell transplantation. The Laboratory of Pediatric Hemato-Oncology of the University of Padua is the AIEOP (Italian Association for Pediatric Hemato-Oncology) referring laboratory and up to 5,000 pediatric leukemia samples are processed every year. For all the ALL diagnosis and relapse samples DNA index is analysed for the risk-treatment stratification of the patients. The analysis evaluates both DNA ploidy and the proliferative state through the determination of the cell population in the S-phase of the cell cycle. Cell cycle analysis of childhood ALL, performed in our laboratory, reveal that S-phase is significant increased in bone marrow from relapsed patients compared to bone marrow of the same patients at the diagnosis. The study of the molecular mechanisms involved in S-phase increase at relapse will help us to improve our knowledge about relapse mechanism and to design new therapeutic strategy exploiting these changes in cell cycle control. We studied 180 patients affected by B-ALL enrolled in AIEOP protocols with more that 60% of blast cells in the bone marrow, both at diagnosis and relapse; extramedullary relapses were excluded. Cell cycles were analysed by flow citometry. To evaluate changes in cell cycle distribution at relapse in respect to diagnosis, for each patients we calculate ΔS as the difference between S-phase fraction at relapse and S-phase fraction at diagnosis. Gene expression profiling were performed using Human Genome U133 Plus 2.0 array (Affymetrix platform). Gene expression analysis, real time PCR and western blot were carry out to compare higher and lower ΔS patients. Preliminary gene expression analysis, on higher ΔS vs lower ΔS samples of relapsed patients, identified 58 differentially expressed probe sets corresponding to genes involved in proliferation, DNA damage and cell migration (LFDR<0.05). Among these genes, we found some E2F1 targets such as MAD2L1, CIP2a and RFC3. Western blot and real time PCR revealed increased cyclinA2 expression, another E2F1 target, in samples from relapsed patients with higher ΔS. We observed that higher [[Unable to Display Character: ∆]]S correlate to very early time to relapse (within 18 month from diagnosis) and these patients are classified as high risk patients that barely respond to treatments after relapse. Very early relapse more frequently happens during maintenance therapy based on methotrexate and 6-mercaptopurine, and methotrexate resistance could be mediated by increased levels of E2F1 transcriptional activity. At the present stage we identified S-phase increase as a molecular determinant of high risk in B-ALL relapse. Further studies of these alterations of cell cycle control and of E2F1 activation may help the development of more specific and less toxic therapies that overcome resistance to currently used chemotherapeutics. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B62. Citation Format: Roberta Bortolozzi, Giampietro Viola, Maddalena Paganin, Silvia Bresolin, Silvia Disarò, Elena Porcù, Valentino Conter, Franco Locatelli, Barbara Buldini, Giuseppe Basso. Cell cycle alterations in paired diagnosis-relapse childhood acute lymphoblastic leukemia. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B62.

Confirmation of a novel recurrent association: BCR-ABL t(9;22) and t(19;21)

Association of a t(9;22)(q34;q11), BCR/ABL-positive, with a dic(19;21)(p13;p13) has been described in acute lymphoblastic leukemia in relapse, raising the question of whether this association is recurrent. Described here are two cases, one of myeloproliferative disease and one of acute lymphoblastic leukemia, both presenting a masked t(9;22) and t(19;21). Chromosomal rearrangements were ascertained by fluorescence in situ hybridization (FISH) using locus-specific probes, multicolor FISH, and bacterial artificial chromosome array. These additional observations suggest a nonrandom association.

Simultaneous Development of Bilateral Retrobulbar and Intradural Spinal Masses Following Donor Lymphocyte Infusions for Acute Lymphoblastic Leukemia Relapsing After Bone Marrow Transplantation

The authors describe a 6-year-old boy with acute lymphoblastic leukemia in relapse after bone marrow transplantation. Complete remission was obtained after reinduction chemotherapy followed by donor lymphocyte infusions. Ten months later, right-sided proptosis and exotropia developed, with back pain and leg paralysis. Computed tomography revealed bilateral orbital masses. Magnetic resonance imaging demonstrated abnormal signal intensity in the T4-6 vertebral bodies and an intradural mass on the left posterior side of the spinal canal. Although bone marrow aspiration was negative, orbital mass biopsies revealed CD10-positive lymphoblasts. Chimerism analysis of bone marrow and peripheral blood showed full donor alleles. Local radiotherapy and chemotherapy resulted in neurologic improvement.

Laparoscopic Adnexectomy of a Persistent Ovarian Tumor in a Girl with Acute Lymphoblastic Leukemia Relapse

The management of children with acute lymphoblastic leukemia (ALL) relapse and an ovarian tumor remains controversial. The authors report about a 4-year-old girl who developed a late bone marrow and cutaneous relapse of her pre-B-cell ALL and revealed an enlargement of her left ovary (4 x 3 x 2 cm). Chemotherapy (ALL-REZ-BFM pilot-protocol 2002) achieved effective remission, but the ovarian mass depicted no regression. Laparoscopic adnexectomy was performed and the tumor could be extracted in a specimen-bag through a 12-mm umbilical incision. Histology detected no viable lymphoblasts, but a fibrotic enlargement due to previous cellular infiltration. The authors conclude that in children with ALL relapse and an ovarian tumor, malignant infiltration as well as local response to chemotherapy can be judged only by surgical excision and histopathologic examination. Laparoscopic oophoradnexectomy is a valuable management option in these children.

Laparoscopic Adnexectomy of a Persistent Ovarian Tumor in a Girl with Acute Lymphoblastic Leukemia Relapse

The management of children with acute lymphoblastic leukemia (ALL) relapse and an ovarian tumor remains controversial. The authors report about a 4-year-old girl who developed a late bone marrow and cutaneous relapse of her pre-B-cell ALL and revealed an enlargement of her left ovary (4 2 3 2 2 cm). Chemotherapy (ALL-REZ-BFM pilot-protocol 2002) achieved effective remission, but the ovarian mass depicted no regression. Laparoscopic adnexectomy was performed and the tumor could be extracted in a specimen-bag through a 12-mm umbilical incision. Histology detected no viable lymphoblasts, but a fibrotic enlargement due to previous cellular infiltration. The authors conclude that in children with ALL relapse and an ovarian tumor, malignant infiltration as well as local response to chemotherapy can be judged only by surgical excision and histopathologic examination. Laparoscopic oophoradnexectomy is a valuable management option in these children.

INK4A/ARF deletions are acquired at relapse in childhood acute lymphoblastic leukaemia: a paired study on 25 patients using real-time polymerase chain reaction.

Current risk-adjusted intensive therapies for childhood acute lymphoblastic leukaemia (ALL) are expected to result in an event-free survival of greater than 75%. In sharp contrast, relapsed paediatric ALL is a difficult disease to treat. In this study, 25 paediatric patients with ALL were analysed at diagnosis and relapse for their p16 (exon 2) status using the most accurate method of detection, real-time polymerase chain reaction (PCR). The median time to relapse for the group was 27 months. At diagnosis, the incidence of p16 homozygous and hemizygous deletion in this group was 32% and 20% respectively. The incidence of homozygous p16 deletion at relapse was 64%. A large number of patients, eight of 16 (50%), developed p16 homozygous deletion at relapse. Of those eight patients, four were hemizygous and four were germline at diagnosis. At diagnosis, those patients with a homozygous or hemizygous p16 deletion relapsed sooner than those germline for p16. We have shown that p16 alterations are frequently present in relapsed lymphoblastic leukaemia in children.

Bone pain caused by isolated paraspinal extramedullary relapse of childhood acute lymphoblastic leukemia

Bone pain caused by isolated paraspinal extramedullary relapse of childhood acute lymphoblastic leukemia

Incidence of TEL/AML1 Fusion Gene Analyzed Consecutively in Children With Acute Lymphoblastic Leukemia in Relapse

The translocation t(12; 21)(p13; q22) is difficult to detect by classic cytogenetics. However, using fluorescence in situ hybridization (FISH) and by screening for the TEL/AML1 rearrangement by the polymerase chain reaction (PCR), it has been demonstrated to be the most frequent known structural chromosomal abnormality in childhood acute lymphoblastic leukemia (ALL). It is closely correlated with a B-cell precursor (BCP) phenotype and is considered a favorable prognostic factor. However, little is known about the incidence of the translocation in relapsed patients and the duration of complete remission (CR) in children expressing the TEL/AML1 fusion gene. We therefore examined 49 bone marrow samples from children with ALL at first or second relapse that were consecutively mailed to our laboratory to test for the presence of t(12; 21) using reverse transcriptase (RT)-PCR. The TEL/AML1 rearrangement could be identified in nine of 44 (20%) of the patients, a result similar to the reported incidence at diagnosis. Most of the TEL/AML1–positive children showed no adverse clinical features at diagnosis (eg, white blood cell [WBC] count <100 × 109/L or age <10 years), and regarding these data, there were no differences versus children who were negative for the fusion gene. However, the period of remission was about 1 year longer in children expressing TEL/AML1 (P = .046), and the majority of relapses in this group appeared late (<2 years after diagnosis). Our findings therefore reinforce the urgent need for further prospective studies with a long follow-up period to determine the true prognostic significance of t(12; 21) and to avoid premature changes of treatment strategies.

Incidence of TEL/AML1 Fusion Gene Analyzed Consecutively in Children With Acute Lymphoblastic Leukemia in Relapse

AbstractThe translocation t(12; 21)(p13; q22) is difficult to detect by classic cytogenetics. However, using fluorescence in situ hybridization (FISH) and by screening for the TEL/AML1 rearrangement by the polymerase chain reaction (PCR), it has been demonstrated to be the most frequent known structural chromosomal abnormality in childhood acute lymphoblastic leukemia (ALL). It is closely correlated with a B-cell precursor (BCP) phenotype and is considered a favorable prognostic factor. However, little is known about the incidence of the translocation in relapsed patients and the duration of complete remission (CR) in children expressing the TEL/AML1 fusion gene. We therefore examined 49 bone marrow samples from children with ALL at first or second relapse that were consecutively mailed to our laboratory to test for the presence of t(12; 21) using reverse transcriptase (RT)-PCR. The TEL/AML1 rearrangement could be identified in nine of 44 (20%) of the patients, a result similar to the reported incidence at diagnosis. Most of the TEL/AML1–positive children showed no adverse clinical features at diagnosis (eg, white blood cell [WBC] count <100 × 109/L or age <10 years), and regarding these data, there were no differences versus children who were negative for the fusion gene. However, the period of remission was about 1 year longer in children expressing TEL/AML1 (P = .046), and the majority of relapses in this group appeared late (<2 years after diagnosis). Our findings therefore reinforce the urgent need for further prospective studies with a long follow-up period to determine the true prognostic significance of t(12; 21) and to avoid premature changes of treatment strategies.

Neuropsychological and neurological outcome after relapse of lymphoblastic leukaemia.

Fourteen children who relapsed after initial remission of leukaemia were studied. Six received a second course of cranial radiotherapy, while the remaining eight children were given total body irradiation before bone marrow transplantation. The postirradiation somnolence syndrome was common after cranial radiotherapy. All children had mild/soft neurological signs, mostly of coordination. None had a major motor disability. All but the youngest child had cataracts; two children required an operation for these. All children were growth hormone deficient. Verbal IQ, attention, and concentration were selectively reduced (with respect to normative levels). The time between the two treatments, age at relapse, and higher doses of radiotherapy all correlated with cognitive outcome, with girls showing greater impairments than boys. Only two children were performing at age appropriate levels on measures of academic achievement. It is concluded that neurological and neuropsychological morbidity is significantly increased by the current treatments prescribed after the relapse of leukaemia.

Detection of minimal residual disease in T-cell acute lymphoblastic leukemia using polymerase chain reaction predicts impending relapse

After achieving remission, approximately one-third of patients with T- cell acute lymphoblastic leukemia (T-ALL) relapse due to the resurgence of residual leukemic cells that cannot be detected in remission by morphologic methods. Thus, the early detection of residual disease is highly desirable to monitor the efficacy of therapy, or to institute an alternative mode of therapy. Toward this aim, we have examined the applicability of polymerase chain reaction (PCR) amplification in the detection of minimal residual disease (MRD) in bone marrow samples from patients with T-ALL in morphologic remission. Two different approaches were taken to identify leukemic clone-specific sequences that could be used as targets for PCR amplification. The first technique used T-cell receptor-delta (TCR-delta) gene rearrangements that were sequenced directly after PCR amplification of leukemic DNA. This method was successful in generating clone-specific probes for 76% of T-ALL patients screened. An alternative method was used to clone and sequence a TCR-beta chain gene from leukemic cells to generate a specific probe. The PCR assays that we used were specific for each patient's leukemic clone, and were capable of routinely detecting one leukemic cell in 10(4) normal cells. Using these sensitive PCR-based assays, we found no evidence for persistence of the leukemic clone in any of the bone marrow samples from four T-ALL patients who are in long-term (3.9 + to 8.1 + years) remission. In contrast, we detected residual disease in clinical remission samples from two patients who subsequently relapsed. In one patient, where we had appropriate samples, we observed a dramatic expansion of the leukemic clone 3 months before clinical relapse. These results suggest that PCR-based assays for detection of MRD in T-ALL patients have great potential in predicting impending relapse, and in determining the efficacy of the anti-leukemic therapy. These methods may also allow the identification of long-term survivors.

Cytogenetic studies of 21 patients with acute lymphoblastic leukemia in relapse

Karyotypes of 21 patients, originally entered into the Third International Workshop on Chromosomes in Leukemia (3IWCL), were investigated in first, second and/or subsequent relapses. Karyotypes at diagnosis were related to the relapses in the following ways: normal to normal (N-N) (five cases); abnormal to normal (A-N) (two cases); abnormal to abnormal with no change (A-A) (five cases); abnormal to abnormal with clonal evolution (A-A+) (eight cases); and normal to abnormal (N-A) (one case). The A-A group comprised two each of t(4;11) and t(9;22) cases and one pseudodiploid case; included in this group were the only two patients who did not receive intensive treatment. Both A-N cases had been pseudodiploid at diagnosis. Clonal evolution A-A+ occurred in patients who had had 47–49 chromosomes or pseudodiploidy at diagnosis and was mainly due to the addition of structural change. The additional abnormalities were different in each case. The only de novo appearance of a clone (N-A) was in host cells in relapse following bone marrow transplantation. Clonal evolution occurred in patients who had been intensively treated and who relapsed late; the median time from diagnosis to relapse studied for the A-A group was 6 months and for the A-A+ group was 24 months. Survival following relapse was shorter for patients who had had a clonal abnormality at any time (median 10 months) than for those with no abnormality at diagnosis or in relapse (median 26 months).

Prognosis and treatment after relapse of acute lymphoblastic leukemia and non-Hodgkin's lymphoma: 1985. A report from the Childrens Cancer Study Group.

Acute lymphoblastic leukemia and non-Hodgkin's lymphoma constitute 42% to 45% of the cancers in infants, children, and adolescents: In 1985, an estimated 2025 children were newly diagnosed with these two cancers and 900 (43%) of the pediatric cancer deaths in the United States have been projected to be due to these diseases. The single most important obstacle to preventing these deaths is relapse, and prevention of relapse or salvage of the patient who has had a relapse continues to be a major therapeutic challenge. The most important initial step in the treatment of the child whose disease has relapsed is to determine, to the extent possible, the prognosis. In a child with non-Hodgkin's lymphoma, a relapse confers an extremely poor prognosis, regardless of site of relapse, tumor histology, or other original prognostic factors, prior therapy, or time to relapse. In the child with acute lymphoblastic leukemia in relapse, the prognosis depends on multiple factors. The primary therapy is chemotherapy or chemoradiotherapy with marrow grafting. Other options exist, including no therapy, or investigational therapy. The therapy selected should be predicated on the prognosis. In the child with an isolated central nervous system (CNS) relapse off therapy, minimum therapy should be administered, particularly if the relapse occurred without prior cranial irradiation. In the child whose relapse is more than 6 months off therapy, conventional therapy should be considered. Also, a patient with an isolated CNS relapse on therapy after prior cranial irradiation should be given moderate therapy. Bone marrow transplantation or high-dose chemoradiotherapy with autologous marrow rescue should be reserved in children with a second or subsequent extramedullary relapse, and possibly for those with a first isolated overt testicular relapse on therapy.

Cytogenetic studies in bone marrow transplant recipients.

Chromosome studies were performed in 24 patients who underwent allogeneic bone marrow transplantation (BMT) for severe aplastic anaemia (8), chronic myeloid leukemia (5 in chronic, 2 in accelerated phase and 1 in lymphoid blast crisis), acute myeloid leukemia (6), acute lymphoblastic leukemia in relapse (1) and Hodgkin's disease (1). Donor-cell type engraftment was demonstrated in 21 patients: in all 17 sex-mismatched transplants and - as demonstrated by reconstitution with Ph-negative cell populations - in 4 CML patients with a sex-matched donor. Recipient-type mitoses were seen in the bone marrow of 5 cases (1 SAA, 3 CML, 1 AML) after transplantation. They were only observed on one occasion in patients with SAA (4 of 25 on day 33) and AML (44 of 50 on day 14). Despite the continued demonstration of some Ph-positive mitoses in 3 patients with CML up to day 28, 323 and 451 after BMT, respectively, all surviving CML patients are still in complete haematological and clinical remission. So far the significance of these cytogenetically abnormal persisting host cells remains unknown.