Search PubMed⌕ Search

Biomedical subjects

S J Forman

Publications and source records attributed to S J Forman.

At least 91 records · Page 5Linked to original sources
PubMed1997

The role of allogeneic bone marrow transplantation in the treatment of high-risk acute lymphocytic leukemia in adults.

Studies in the last decade show that most adults with acute lymphocytic leukemia (ALL) can achieve remission with intensive induction chemotherapy. Depending on the risk factors present at diagnosis in an individual patient, continued remissions range from less than 10% to more than 50%. The following factors have been shown to be predictive of relapse: high white cell count at diagnosis, age beyond 30, extramedullary disease at presentation, unfavorable chromosomal translocations, time longer than 6 weeks to enter remission, and use of less intensive chemotherapy for induction. Studies have been conducted to determine whether allogeneic bone marrow transplantation (BMT) could improve the outcome for patients with high-risk ALL when performed during first remission. These studies have shown that these patients have a 40% to 60% chance of disease-free survival. The current recommended strategy for patients with high-risk ALL in first remission is to undergo bone marrow transplantation prior to relapse. For those in second and subsequent remissions or those who do not achieve remission, allogeneic BMT still offers the best chance for cure of the disease.

Adult↗
PubMed1997

Ribozyme-mediated inhibition of a Philadelphia chromosome-positive acute lymphoblastic leukemia cell line expressing the p190 bcr-abl oncogene.

The bcr-abl oncogene is the molecular counterpart of the Philadelphia chromosome (Ph), which is detected in > 95% of patients with chronic myelogenous leukemia (CML) and 20-30% of adults with acute lymphoblastic leukemia (ALL). Leukemic cells from patients with CML express the p210 form of the bcr-abl oncogene, whereas in adult Ph+ ALL approximately 50% of cases express the p190 form of the bcr-abl oncogene, and the other 50% express the same p210 gene as is found in CML. In this study, we have designed hairpin ribozymes (RZs) specific for the p190 form of the bcr-abl oncogene to inhibit the growth of a p190 Ph+ ALL cell line, Sup-B15. The RZs cleave p190 RNA substrate in a cell-free in vitro assay. In the presence of the liposome, DMRIE-C, the RZs are protected from serum mediated catalysis in vitro. Anti-p190 RZs transfected with DMRIE-C as the vector into K562 cells, which express the p210 bcr-abl oncogene, are stable intracellularly for up to 96 hours. Up to 33% of the DMRIE-C and RZ mixtures are taken up by Sup-B15 cells cultured in suspension. Expression of the p190 bcr-abl protein product is specifically inhibited as demonstrated by Western blot analysis. Cell growth of the Sup-B15 cells is completely inhibited by anti-p190 RZs over four days in culture. Anti-p210 RZs have no significant effect on bcr-abl protein expression or cell growth by Sup-B15 cells. RZs may have a role in purging stem cell populations collected from patients with Ph+ ALL in the context of autologous bone marrow transplantation.

Blotting, Western↗
PubMed1997

Fractionated total-body irradiation, etoposide, and cyclophosphamide followed by allogeneic bone marrow transplantation for patients with high-risk or advanced-stage hematological malignancies.

Myeloablative therapy followed by allogeneic bone marrow transplantation (BMT) has proven to be curative therapy in patients with hematologic malignancies. Relapse, however, remains a major cause of treatment failure for patients with advanced disease. During the past 15 years, we have gained considerable experience with the combination of fractionated total-body irradiation (FTBI) and etoposide followed by allogeneic BMT for hematologic malignancies. In an attempt to decrease post-transplant relapse rates, 67 patients under the age of 50 years with high-risk or advanced-stage hematological malignancies received an intensified regimen of FTBI and etoposide plus cyclophosphamide followed by BMT from a genotypically-matched related donor. The regimen consisted of 1320 cGy of FTBI in 11 fractions, 60 mg/kg of etoposide (VP-16), and 60 mg/kg of cyclophosphamide (CY). Fifty-three patients received cyclosporine and prednisone for graft-vs.-host disease (GVHD) prophylaxis and 14 patients received cyclosporine, methotrexate, and prednisone. Diagnosis at BMT included 45 patients with acute leukemia, 7 patients with chronic leukemia, and 15 patients with high-grade non-Hodgkin's lymphoma (NHL). Actuarial disease-free survival (DFS) at 3 years was 42% +/- 12% for the entire group with a median follow-up of 50 months (range 20-74) for 28 patients who remain alive in continued complete remission (CR). Actuarial 3-year-DFS was 38% +/- 14% in 52 patients with acute or chronic leukemia and 60% +/- 25% in 15 patients with NHL with relapse rates of 45% +/- 16% and 21% +/- 11%, respectively. DFS at 3 years was 40% +/- 18% in 32 patients with acute leukemia in 1st relapse or 2nd CR or chronic myelogenous leukemia in accelerated phase, and was 32% +/- 22% in 20 patients with more advanced disease. Regimen related mortality occurred in 9 patients (4, veno-occlusive disease of the liver; 2, multi-organ failure; 1, diffuse alveolar hemorrhage; 1, central nervous system (CNS) hemorrhage; 1, adult respiratory distress syndrome (ARDS). The combination of FTBI, etoposide, and cyclophosphamide followed by allogeneic BMT is an effective and relatively well-tolerated regimen for patients with advanced hematologic malignancies. The role for this regimen should be further defined by prospective clinical trials.

Adolescent↗
PubMed1996

Acute polyneuropathy after high dose cytosine arabinoside in patients with leukemia.

BACKGROUND: Peripheral nerve toxicity has been reported but is not a commonly recognized complication of high dose cytosine arabinoside (HDAC) therapy. This study was undertaken to estimate the prevalence and describe the clinical spectrum of acute polyneuropathy associated with HDAC therapy for leukemia. METHODS: Records of 153 acute leukemia patients who received 194 courses of HDAC at the City of Hope were reviewed for evidence of severe peripheral neuropathy with onset 2-3 weeks after HDAC therapy. RESULTS: Two patients were identified who developed motor disability 2-3 weeks after HDAC therapy, and the disability progressed in a monophasic course to quadriparesis. There was neurophysiologic evidence of peripheral nerve demyelination with slowed nerve conduction velocities and conduction block. One patient who was autopsied had demyelination identified in luxol-fast blue sections of peripheral nerve (with Bielschowsky-stained sections showing intact peripheral nerve axons). There were foamy macrophages in the peripheral nerve but no chronic inflammatory cells. For comparison, data from these two patients were combined with those from four published case reports of polyneuropathy associated with HDAC therapy. Quadriparesis occurred in five of six cases with the need for ventilatory support in four. Cerebrospinal fluid protein was elevated in five of six cases. Etiologic evidence incriminating HDAC included simultaneous cerebellar signs in two of six cases and a narrow interval of clinical onset after HDAC therapy. CONCLUSIONS: Demyelinating polyneuropathy occurs in approximately 1% of HDAC courses and produces severe motor disability. HDAC immunosuppression could trigger an immune-mediated neuropathy; alternatively, a direct neurotoxic effect of HDAC on Schwann cells is also an etiologic possibility.

Acute Disease↗
PubMed1996

Integration of adeno-associated virus vectors in CD34+ human hematopoietic progenitor cells after transduction.

Gene transfer vectors based on adeno-associated virus (AAV) appear promising because of their high transduction frequencies regardless of cell cycle status and ability to integrate into chromosomal DNA. We tested AAV-mediated gene transfer into a panel of human bone marrow or umbilical cord-derived CD34+ hematopoietic progenitor cells, using vectors encoding several transgenes under the control of viral and cellular promoters. Gene transfer was evaluated by (1) chromosomal integration of vector sequences and (2) analysis of transgene expression. Southern hybridization and fluorescence in situ hybridization analysis of transduced CD34 genomic DNA showed the presence of integrated vector sequences in chromosomal DNA in a portion of transduced cells and showed that integrated vector sequences were replicated along with cellular DNA during mitosis. Transgene expression in transduced CD34 cells in suspension cultures and in myeloid colonies differentiating in vitro from transduced CD34 cells approximated that predicted by the multiplicity of transduction. This was true in CD34 cells from different donors, regardless of the transgene or selective pressure. Comparisons of CD34 cell transduction either before or after cytokine stimulation showed similar gene transfer frequencies. Our findings suggest that AAV transduction of CD34+ hematopoietic progenitor cells is efficient, can lead to stable integration in a population of transduced cells, and may therefore provide the basis for safe and efficient ex vivo gene therapy of the hematopoietic system.

Amino Acid Sequence↗
PubMed1996

Molecular analysis of T-cell receptor repertoire in bone marrow transplant recipients: evidence for oligoclonal T-cell expansion in graft-versus-host disease lesions.

We have analyzed the T-cell receptor (TCR) V beta repertoire using polymerase chain reaction (PCR) in a cohort of eight patients receiving allogeneic bone marrow transplantation (BMT) from related and unrelated donors at the City of Hope. Results of PCR studies from graft-versus-host disease (GVHD) skin lesions show a bias in the usage of TCR V beta families, whereas examination of peripheral blood (PB) withdrawn at the same time did not reveal a similar phenomenon. In one such family, TCR V beta 2 is predominantly expressed in 7 of 7 biopsy specimens examined. V beta 2 TCR expression from these patients was analyzed more extensively using a combination of individual TCR gene cloning, followed by sequence analysis. We found evidence of oligoclonal expansion of single V beta 2-bearing TCRs in GVHD lesions, and in the PB of some patients after diagnosis of GVHD. In contrast, GVHD-negative biopsy samples showed no evidence for clonotypic TCR amplification. Sequence-specific TCR CDR3 region probes were derived from analysis of the predominant expressed TCR in GVHD lesions, and used to probe Southern blots of amplified V beta 2 TCR mRNA from PB and tissue from BMT recipients and their respective donors. In most cases the probes are highly specific in detecting TCR expression from GVHD lesions alone, although in several instances expression could be detected in PB after GVHD diagnosis. These data provide supporting evidence for the hypothesis that acute GVHD is associated with expansion of T-cell clones expressing antigen-specific TCRs that may contribute to the disease pathology.

Adolescent↗
PubMed1996

Polymyositis as a manifestation of chronic graft-versus-host disease.

A syndrome indistinguishable from idiopathic polymyositis occurred in 11 patients as a manifestation of chronic GVHD. All patients had elevation of creatine phosphokinase (CPK). Immunohistology demonstrated the effector cells in the muscle infiltrates as cytotoxic T cells, a finding similar to idiopathic polymyositis. Polymyositis is a rarely reported complication of chronic graft-versus-host disease (GVHD) with only 8 cases described in the literature. We encountered this syndrome in a small but significant percentage of our patients with chronic GVHD. Polymyositis associated with chronic GVHD does not affect the overall prognosis for the patient. Moreover, polymyositis can be the only manifestation of chronic GVHD. Awareness of this complication is important because it can be confused with other causes of muscle weakness after bone marrow transplantation. Finally, prompt initiation of corticosteroid therapy results in a rapid improvement of the associated symptoms.

Adolescent↗
PubMed1996

Myelodysplastic syndrome.

Myelodysplasia is being increasingly recognized as an important disease not only in the elderly but also in younger patients. It is also being seen more commonly as a complication of treatment with chemotherapeutic agents. Recent advances have distinguished between the different forms of therapy-related myelodysplasia as well as their genetic associations. Although allogeneic bone marrow transplantation using either related or unrelated donors offers the only chance for cure of this disease, cell biology studies also indicate that there is a normal stem cell compartment in the bone marrow of patients with myelodysplasia. Future studies may offer the opportunity for autologous stem cell transplantation for patients achieving remission after induction chemotherapy.

Humans↗
PubMed1996

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission.

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.

Adolescent↗
PubMed1996

Myelodysplasia and acute myeloid leukemia occurring after autologous bone marrow transplantation for lymphoma.

Secondary hematopoietic disease manifesting as acute myeloid leukemia, myelodysplastic syndrome or clonal karyotypic abnormalities, has been recently recognized as a relatively frequent and potentially serious complication of autologous bone marrow transplantation for both Hodgkin's disease and non-Hodgkin's lymphoma. The available evidence suggests the disease results primarily from repeated exposure of the host stem cells to therapeutic agents before the time of transplant, but a conspiratory role for the transplantation procedure itself cannot be entirely excluded. Strategies to decrease the incidence of secondary hematopoietic disease include earlier stem cell harvest and/or transplantation, and the performance of screening karyotypic studies on the bone marrow prior to autologous grafting.

Acute Disease↗
PubMed1996

Paradoxical effect of thalidomide prophylaxis on chronic graft-vs.-host disease.

Thalidomide has been reported to be an effective agent for the treatment of chronic graft-vs.-host disease (GVHD). To determine its efficacy as a prophylactic agent for the prevention of chronic GVHD, a prospective randomized double-blind study was performed. A total of 59 patients were randomized to receive either placebo or thalidomide (200 mg orally twice a day) beginning 80 days after allogeneic bone marrow transplantation (BMT). Fifty-four evaluable patients were analyzed, 26 received placebo, and 28 received thalidomide. The characteristics of patients were well-balanced between the two groups. Following the first interim analysis conducted by the Data Safety Monitoring Board using an intent-to-treat approach, a statistically significant difference in the incidence of chronic GVHD was found. Patients receiving thalidomide developed chronic GVHD more often than patients receiving placebo (p = 0.06). Moreover, an apparent overall survival advantage was noted for patients receiving placebo compared to those receiving thalidomide (p = 0.006). Adjustment for possible confounding factors did not eliminate these negative effects of thalidomide. These results demonstrate that while thalidomide is an effective agent for the therapy of chronic GVHD, its use at the doses administered for the prophylaxis of chronic GVHD resulted in a paradoxical outcome with a higher incidence of chronic GVHD and a lower overall survival. We conclude that the early use of thalidomide results in a shift in the balance between GVHD and induction of tolerance. These data demonstrate again the importance of phase III double-blind controlled randomized studies.

Adolescent↗
PubMed1995

Thalidomide as salvage therapy for chronic graft-versus-host disease.

Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment.

Adolescent↗
PubMed1995

High-dose therapy and autologous bone marrow transplantation for Hodgkin's disease patients with relapses potentially treatable by radical radiation therapy.

PURPOSE: A retrospective review evaluated the results of autologous bone marrow transplantation (A-BMT) for patients with relapsed Hodgkin's disease (HD) who were potentially treatable by radical radiation therapy (RRT). METHODS AND MATERIALS: Evaluated patient cases met the following criteria: initial treatment with chemotherapy (with or without involved field radiation therapy < 25 Gy); no history of bone marrow or extensive lung involvement; no current or previous evidence of systemic metastases except liver; radiation therapy used with salvage chemotherapy for prior relapse would not preclude use of RRT (e.g., > 20 Gy to spinal cord); HD at time of salvage therapy limited to lymph nodes, Waldeyer's ring, liver, spleen, direct extension sites, and/or one lung. RESULTS: There were 23 A-BMT patients treated between 1986 and 1991 who fulfilled the criteria. Three (13%) patients died from treatment-related complications and eight (35%) developed nonfatal Grade 3-4 complications. The 3-year actuarial disease-free survival rate was 61%. The 3-year disease-free survival rate was 55% for the nine patients with at least one prior disease-free interval (DFI) > 12 months, 67% for nine patients with DFI < 12 months, and 60% for five induction failure patients (p > 0.10). These results are comparable to retrospective studies of RRT results in selected relapsed HD patients. CONCLUSIONS: Long-term disease-free survival is frequently possible with either A-BMT or RRT in appropriately selected relapsed HD patients. In considering treatment options, important prognostic factors include initial stage of disease, number of prior relapses, DFI, and extent of relapsed disease.

Adolescent↗
PubMed1995

Immunohistochemical analysis of T cell phenotypes in patients with graft-versus-host disease following allogeneic bone marrow transplantation.

Allogeneic bone marrow transplantation has become the therapy of choice in many cases of hematologic malignancy. In both matched related donor transplants--and, to a greater degree, in unrelated donor transplant situations--a major complication of the procedure is GVHD. This problem is caused by mature T cells in the graft, which also facilitate engraftment, and mediate an antitumor effect to reduce relapse. In order to further characterize the T cells that are present at the GVHD site of injury, we have studied 134 fresh tissue biopsies using immunohistochemical methods from 50 consecutive ABMT recipients clinically suspected of having acute GVHD. Antibodies specific for T cells, T cell receptor subsets, B cells, and NK cells were used to characterize the lymphocytic infiltrate in the biopsy tissue from GVHD patients. The data showed that the majority of lymphocytes that had infiltrated the epithelium or epidermis were CD3+ T cells. Using antibodies that distinguished the alpha/beta (beta F1) from the gamma/delta TCR (TCR delta 1)-expressing T cells, we observed that the lymphocytic infiltrates from involved tissues of the gastrointestinal tract, skin, and liver are almost exclusively derived from the alpha/beta expressing T cell subset, and are of the memory cell subset of T cells (CD45RO). This is in contrast to some examples from other disease states, in which a significant proportion of the lymphocytes that infiltrate the epidermal layers are of the gamma/delta type.

Adolescent↗
PubMed1995

Cytogenetic correlation with disease status and treatment outcome in advanced stage leukemia post bone marrow transplantation: a Southwest Oncology Group study (SWOG-8612).

A retrospective cytogenetic study was performed to determine whether non-random chromosome aberrations were related to the outcome of marrow transplantation for advanced stage acute leukemia (AL) and chronic myelogenous leukemia (CML). The patients were registered on SWOG-8612, a randomized comparison of busulphan and cyclophosphamide (BU/CY) to fractionated total body irradiation and etoposide (FTBI/VP16) as preparatory regimens for allogeneic bone marrow transplant (BMT). Blume K. G., Kopecky K. J., Henslee-Downey J. P., Forman S. J., Stiff P. J., Le Maistre C. F. & Appelbaum F. R. (1987) Blood 81, 2187. Pretreatment cytogenetic studies were available for 90 (78%) of the 115 patients who proceeded to BMT. Patients were categorized by diagnosis (ALL/AML/CML), disease status ['good' risk = second complete remission (CR2) or CML-accelerated phase (AP); 'poor' risk = third complete remission (CR3), induction failure, florid relapse or CML-blast phase (BP)] and cytogenetic status (favorable = normal cytogenetics in AL or Philadelphia chromosome positive (Ph+) standard or variant translocation as the sole findings in CML; unfavorable = all other cytogenetic aberrations). Chromosomal aberrations observed in the unfavorable category included -7, t(9;22) in AL, t(8;21) in association with complex karyotypes, t(6;9), del(9q), t/del(11q), t(1;19), hypotetraploidy, and complex karyotypes (> 3 cytogenetic anomalies). Unfavorable cytogenetic status was significantly more frequent among patients with 'poor' risk clinical disease status (P < 0.0001). In multivariate analysis, disease-free survival (DFS) was significantly poorer for patients with unfavorable cytogenetic status (P = 0.002) but not significantly related to disease status (P = 0.43). These data indicate that certain secondary chromosome aberrations [+8,i(17q), duplication of Ph] should be reclassified as relatively favorable predictors of successful BMT in CML and, therefore, be separated from the unfavorable cytogenetic aberrations characteristic of drug resistant disease [-7, inv(3), complex karyotypes]. The limited number of patients precluded definitive assessment of the prognostic significance of specific cytogenetic aberrations for any single diagnosis. Nevertheless, these findings suggest that cytogenetic status may be an important and independent factor in predicting outcome following allogeneic bone marrow transplantation.

Adolescent↗
PubMed1995

Involved field radiation therapy for Hodgkin's disease autologous bone marrow transplantation regimens.

From 1986 through 1992, involved-field radiation therapy (IF-RT) was administered to 29 of 86 patients with recurrent Hodgkin's disease (HD) who received a high-dose cyclophosphamide/etoposide regimen with autologous bone marrow transplantation (A-BMT). Patients without a significant history of prior RT received total body irradiation (TBI), initially as a single dose 5-7.5 Gy, and subsequently with fractionated TBI (F-TBI) delivering 12 Gy. Previously irradiated patients received a high-dose BCNU regimen instead of TBI. IF-RT was employed selectively, usually for sites of bulky disease (> 5 cm). IF-RT doses were typically 20 Gy at 2 Gy per fraction for TBI patients and 30-40 Gy at 1.8-2.0 Gy per fraction for non-TBI Patients. Fatal complications developed in four patients while second malignancies have developed in two. The region which received IF-RT was the site of first recurrence in only two cases (7%). With a median follow-up of 28 months, the two-year disease-free survival rate was 44%. For the 22 patients treated by either F-TBI or high-dose BCNU, the 2-year disease-free survival rate was 50% with a median follow up of 29 months. Selective use of IF-RT may increase the chances of complete remission and disease free survival in HD patients with a history of bulky disease.

Adult↗
PubMed1995

Trisomy 11: an association with stem/progenitor cell immunophenotype.

The clinicopathological features and the prognostic significance of acute myeloid leukaemia (AML) with trisomy 11 are currently unknown. In this study we describe 15 adult AML cases with trisomy 11. Trisomy 11 was the sole chromosomal anomaly in eight cases; the remaining seven cases were characterized by +11 in association with other karyotypic aberrations. Patients ages ranged from 34 to 79 years. 12 patients were male; three were female. Although there was no correlation of trisomy 11 with any specific FAB subgroup [M2 (n = 7), M1 (n = 5), M4/5 (n = 2), M3 (n = 1)] less mature forms predominated. Immunologically, the leukaemic blasts showed a strikingly consistent stem cell phenotype with expression of HLA-DR, CD34 and the myeloid antigens (CD15, CD33 and/or CD13). In addition, two cases expressed the B-cell associated antigen CD19. The presence of trilineage dysplasia, suggesting the presence of an underlying myelodysplasia (MDS), was observed at presentation in five cases; in another case MDS was evident at relapse only. Unexpectedly, MLL gene rearrangements were observed in two of four cases characterized by trisomy 11 as the sole karyotypic abnormality; however, MLL aberrations were not identified in three cases with trisomy 11 accompanied by other karyotypic anomalies. The majority of patients in each subgroup (i.e. those with and without additional cytogenetic abnormalities) achieved a short first complete remission (CR) (mean 8 months) and failed to obtain a second CR. Only one patient in each trisomy 11 subgroup is in a continuous CR for > 34 months. These findings suggest that trisomy 11 leukaemia is characterized by a stem/progenitor cell immunophenotype with poor response to standard chemotherapeutic regimens and an unfavourable prognosis.

Acute Disease↗