Overall Remission Rate Research Articles

Retrospective Review of Angiommunoblastic T-Cell Lymphoma: The MD Anderson Cancer Center Experience.

Angioimmunoblastic T-cell Lymphoma (AITL) represents about 4–6% of all lymphomas, but up to 15–20% of all T-cell lymphomas. AITL usually presents in the 6th to 7th decade of life as an advanced stage, systemic disease with B-symptoms, lymphadenopathy, bone marrow involvement, rash, and autoimmune abnormalities. The disease follows an aggressive course and typically portends a poor prognosis. Nevertheless, there are no widely accepted treatment guidelines that have shown significant efficacy or improved benefit in this disease.We report our single institution experience with AITL over the past 10 years.We identified 33 cases of AITL seen at MDACC from 1996–2006. We retrospectively reviewed these cases to analyze clinicopathologic characteristics, treatment regimens, and response rates. The median age at diagnosis was 67 years (43–79), and there was a male to female ratio of 2:1. Thirty-two patients (97%) presented with stage 3 or 4 disease, 16 patients (49%) had bone marrow involvement, and 23 patients (70%) had B symptoms at presentation. Stratifying 32 patients by IPI, 12.5% were classified as low risk, 43.8% as low-intermediate, 28% as high-intermediate, and 15.6% as high risk. A skin rash was present in 16 patients (49%), while 4 patients (12%) had significant inflammatory arthralgias, and 5 patients (15%) had an autoimmune hematologic disorder. Interestingly, 6 patients (18%) had known exposure to industrial chemicals, 8 patients (24%) had a preceding or concurrent second malignancy, and 13 out of the 15 cases (87%) tested for EBV were positive for EBV RNA. Most patients were treated with an anthracycline based regimen. Of these, 6 patients were treated with an intense, alternating triple therapy regimen, 4 patients received a hyperfractionated cyclophosphamide based regimen, and 16 patients received a CHOP-like regimen. Of these 16 patients, 4 also received rituximab in combination with CHOP. Out of 25 evaluable patients after 1st line therapy, 17 patients (68%) achieved CR, 6 patients (24%) achieved PR, and 2 patients (8%) were found to be primary refractory. In those patients with CR, the median duration of 1st remission was 30.5 months (1–96), with a median follow up of 37.6 months (2–101). The probabilities of 1,2, and 3 year survival were 80%, 67%, and 57% respectively. The duration of remission by type of therapy was found to be higher in patients receiving the more intense chemotherapy regimens when compared to CHOP alone. Overall survival of patients treated with CHOP vs. non-CHOP regimens is shown in figure 1. Although the length of followup is still short, notably, only 1 out of 4 patients treated with rituximab have relapsed. The one case had skin-only relapse and has achieved a 2nd remission. The one patient who was treated with upfront high dose chemotherapy and autologous transplant continues to maintain one of the longest durations of remission in our series. Overall response rate and duration of remission in our series was slightly higher than that reported in the literature. Strategies such as early referral to transplant and addition of rituximab to CHOP-like regimens need to be investigated further, as we work to improve the outcome of this disease. [Display omitted]

The prognostic importance of the CA19–9 tumour marker and its use as a biochemical indicator of treatment response during (chemo-) radiotherapy of locally advanced pancreatic cancer

4177 Introduction: CA19–9 has been shown to have prognostic and predictive importance in pancreatic cancer patients undergoing chemoradiotherapy for unresectable locally advanced disease. Patients and Methods: CA19–9 tumour marker kinetics (Roche, Elecsys 2010) were investigated in 171 pancreatic cancer patients immediately before and after radiotherapy as well as 4–8 weeks after end of radiotherapy. Three modalities of treatment were analysed: 37 pts received radiotherapy (RT) alone, 58 pts simultaneous chemoradiotherapy (CRT), and further 76 pts received chemoradiotherapy followed by systemic chemotherapy (CRT-CT). Biochemical response to treatment was determined in accordance to the criteria published by Ishii et al. (Hepatogastroenterology 44: 279–283, 1997), where a >50% decline of CA19–9 from baseline levels was evaluated as a partial response. Pts not expressing elevated CA19–9 levels (cut-off = 37 U/L)were evaluated separately (n=29). Results: Median CA19–9 levels measured immediately before and after radiotherapy as well as 4–8 wks after end of treatment were: 308 U/l, 226 U/l, and 145 U/l, respectively. The analysis of CA19–9 tumour marker kinetics in the treatment groups RT, CRT, and CRT-CT indicated stable disease (SD) in 25%, 35,4%, and 33,4% of pts which was accompanied by an overall remission rate (ORR) of 0%, 31,3 %, and 43,1%, respectively. Interestingly, the biochemical response status had no impact on overall survival (OS). Initial CA19–9 measured before treatment start did not predict response or progression-free survival (PFS). Compared to the group with elevated CA19–9 levels, pts without CA19–9 elevation had a significantly longer PFS (13.1mos vs 8.9 mos, p=0.012) and OS (15.4 mos vs 11.5 mos, p=0.02). Conclusions: Non-pathological CA19–9 levels measured before treatrment start appear to be a favourable prognostic parameter in locally advanced pancreatic cancer treated with (chemo-) radiotherapy. While CRT and CRT-CT was more effective to induce a biochemical response than RT alone, this did not influence survival. No significant financial relationships to disclose.

The prognostic importance of the CA19–9 tumour marker and its use as a biochemical indicator of treatment response during (chemo-) radiotherapy of locally advanced pancreatic cancer

4177 Introduction: CA19–9 has been shown to have prognostic and predictive importance in pancreatic cancer patients undergoing chemoradiotherapy for unresectable locally advanced disease. Patients and Methods: CA19–9 tumour marker kinetics (Roche, Elecsys 2010) were investigated in 171 pancreatic cancer patients immediately before and after radiotherapy as well as 4–8 weeks after end of radiotherapy. Three modalities of treatment were analysed: 37 pts received radiotherapy (RT) alone, 58 pts simultaneous chemoradiotherapy (CRT), and further 76 pts received chemoradiotherapy followed by systemic chemotherapy (CRT-CT). Biochemical response to treatment was determined in accordance to the criteria published by Ishii et al. (Hepatogastroenterology 44: 279–283, 1997), where a >50% decline of CA19–9 from baseline levels was evaluated as a partial response. Pts not expressing elevated CA19–9 levels (cut-off = 37 U/L)were evaluated separately (n=29). Results: Median CA19–9 levels measured immediately before and after radiotherapy as well as 4–8 wks after end of treatment were: 308 U/l, 226 U/l, and 145 U/l, respectively. The analysis of CA19–9 tumour marker kinetics in the treatment groups RT, CRT, and CRT-CT indicated stable disease (SD) in 25%, 35,4%, and 33,4% of pts which was accompanied by an overall remission rate (ORR) of 0%, 31,3 %, and 43,1%, respectively. Interestingly, the biochemical response status had no impact on overall survival (OS). Initial CA19–9 measured before treatment start did not predict response or progression-free survival (PFS). Compared to the group with elevated CA19–9 levels, pts without CA19–9 elevation had a significantly longer PFS (13.1mos vs 8.9 mos, p=0.012) and OS (15.4 mos vs 11.5 mos, p=0.02). Conclusions: Non-pathological CA19–9 levels measured before treatrment start appear to be a favourable prognostic parameter in locally advanced pancreatic cancer treated with (chemo-) radiotherapy. While CRT and CRT-CT was more effective to induce a biochemical response than RT alone, this did not influence survival. No significant financial relationships to disclose.

Cyclophosphamide in steroid-sensitive nephrotic syndrome: outcome and outlook.

Steroid-sensitive nephrotic syndrome often follows a relapsing course with a substantial number of patients requiring cytotoxic therapy with cyclophosphamide (CP). However, the long-term success of CP treatment is difficult to predict. We retrospectively evaluated 106 patients after CP to identify parameters associated with sustained remission. The overall rate of cumulative sustained remission was 24% after 10 years. No gender difference was found. Several factors were significantly correlated with the rate of sustained remission: age at CP therapy (remission 34% versus 9% in children older or younger than 5.5 years, P<0.01), frequently relapsing versus steroid-dependent status (54% versus 17%, P<0.05), leukopenia under CP treatment (44% in children with leukopenia versus 19% in children without leukopenia, P<0.05), and a cumulative dosage per body surface area (BSA) of more or less than 5,040 mg/m(2) (45% versus 11%, P<0.01). In contrast, the cumulative dosage per kilogram body weight had no significant influence on long-term remission (23% in children with >168 mg/kg versus 26% in children with <168 mg/kg, P>0.05). The current concept of CP treatment of steroid-sensitive nephrotic syndrome is less effective in preschool children. CP therapy should be re-evaluated on a BSA-adjusted regimen.

Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test.

Transsphenoidal adenomectomy with resection of a defined pituitary adenoma has been the treatment of choice for CD for the last 30 years. Surgical resection, however, may not always result in long-term remission of CD. This is particularly important in light of the high risk of morbidity and mortality in patients in the unsuccessfully treated cushingoid state. As such, it is interesting to identify prognostic factors that may predict the likelihood of long-term remission. The authors review their series of 174 patients who have undergone transsphenoidal procedures for CD over a period of 20 years with minimum follow-up periods of 5 years. Selection of these patients was based on clinical, imaging, and laboratory criteria that included serum cortisol levels, loss of diurnal variation in serum cortisol levels, urinary free cortisol concentration, and results of a dexamethasone suppression test, petrosal sinus sampling, and corticotroph-releasing hormone stimulation tests as indicated. All patients who met the biochemical criteria underwent transsphenoidal microsurgery. The authors found an overall rate of remission of 74% at 5 years postoperatively. Patients in whom morning serum cortisol concentrations were lower than 3 microg/dl (83 nmol/L) on postoperative Day 3, following an overnight dexamethasone suppression test, had a 93% chance of remission at the 5-year follow-up examination. Patients with cortisol concentrations higher than this level uniformly failed to achieve long-term remission. Transsphenoidal microsurgery is an effective means of control for patients with adrenocorticotrophic hormone-producing microadenomas. Clinical outcome correlated well with the size of the tumor, as measured on preoperative imaging studies, and with postoperative morning cortisol levels following an overnight dexamethasone suppression test. Postoperative cortisol levels can be used as a useful prognostic indicator of the likelihood of future recurrence following transsphenoidal adenomectomy in CD.

Analysis of Treatment Failure in Patients With Minimally Differentiated Acute Myeloid Leukemia (AML-M0)

AbstractReports of treatment of patients with minimally differentiated acute myeloid leukemia (AML-M0) are limited, heterogeneous, and controversial. We verified the prognosis of this subtype by analyzing the results of 189 consecutive patients with de novo AML. Fifteen cases fitting the criteria of AML-M0 were identified. No clinical features distinguished them from other patients with AML. The median age was 61 years (range 27 to 70), with a leukocyte count ranging from 0.6 to 185 × 10 9/L. In all cases the leukemic cells expressed CD34 and reacted with at least one of the antibodies to early myeloid antigens, ie, CD13, CD33, or myeloperoxidase. Immunophenotypic analysis also showed positivity for CD7 in seven samples and the multi-drug-resistance P-glycoprotein (P-170) in six. Cytogenetic analysis was abnormal in 12 of the 13 patients in whom an adequate number of mitoses could be evaluated. No single abnormality prevailed, the most common findings being trisomy 8 (three cases) and aberrations of chromosome 7 (two cases). Antileukemic treatment differed according to age, but for remission induction, all patients received a combination of cytosine arabinoside and an anthracycline or mitoxantrone. The prognosis of patients with AML-M0 was remarkably poor as compared with the other French-American-British subtypes. Whereas the overall rate of complete remission (CR) was 58% with a median survival of 63 weeks, only 6 of the 15 patients with AML-M0 achieved a CR, and the median survival of this group was 16 weeks (range 3 to 39). The major determinant of treatment failure was unresponsiveness to chemotherapy, as only one patient died of infection during the hypoplastic phase. The CR duration of responders was short, ranging from 3 to 22 weeks, and no second remissions were observed. We conclude that conventional combination chemotherapy yields disappointing results in AML-M0. The reason for this may be the convergence of various unfavorable prognostic factors, such as (1) the high incidence of cytogenetic abnormalities; (2) the lack of differentiation features and the expression of immaturity markers such as CD34 and CD7; and (3) the frequent expression of P-170. Nonconventional therapeutic approaches should be developed to alter the prognosis of this form of leukemia.

Analysis of treatment failure in patients with minimally differentiated acute myeloid leukemia (AML-M0)

Reports of treatment of patients with minimally differentiated acute myeloid leukemia (AML-M0) are limited, heterogeneous, and controversial. We verified the prognosis of this subtype by analyzing the results of 189 consecutive patients with de novo AML. Fifteen cases fitting the criteria of AML-M0 were identified. No clinical features distinguished them from other patients with AML. The median age was 61 years (range 27 to 70), with a leukocyte count ranging from 0.6 to 185 x 10(9)/L. In all cases the leukemic cells expressed CD34 and reacted with at least one of the antibodies to early myeloid antigens, ie, CD13, CD33, or myeloperoxidase. Immunophenotypic analysis also showed positivity for CD7 in seven samples and the multidrug-resistance P- glycoprotein (P-170) in six. Cytogenetic analysis was abnormal in 12 of the 13 patients in whom an adequate number of mitoses could be evaluated. No single abnormality prevailed, the most common findings being trisomy 8 (three cases) and aberrations of chromosome 7 (two cases). Antileukemic treatment differed according to age, but for remission induction, all patients received a combination of cytosine arabinoside and an anthracycline or mitoxantrone. The prognosis of patients with AML-M0 was remarkably poor as compared with the other French-American-British subtypes. Whereas the overall rate of complete remission (CR) was 58% with a median survival of 63 weeks, only 6 of the 15 patients with AML-M0 achieved a CR, and the median survival of this group was 16 weeks (range 3 to 39). The major determinant of treatment failure was unresponsiveness to chemotherapy, as only one patient died of infection during the hypoplastic phase. The CR duration of responders was short, ranging from 3 to 22 weeks, and no second remissions were observed. We conclude that conventional combination chemotherapy yields disappointing results in AML-M0. The reason for this may be the convergence of various unfavorable prognostic factors, such as (1) the high incidence of cytogenetic abnormalities; (2) the lack of differentiation features and the expression of immaturity markers such as CD34 and CD7; and (3) the frequent expression of P-170. Nonconventional therapeutic approaches should be developed to alter the prognosis of this form of leukemia.

A Randomized Comparison of Doxorubicin and Doxorubicin-DNA in the Treatment of Acute NonLymphoblastic Leukemia.

In the light of previous findings that treatment of leukemia patients with DNA-linked doxorubicin gave higher doxorubicin concentrations in leukemic cells than treatment with doxorubicin alone, the Leukemia Group of Middle Sweden performed a randomized clinical trial to compare the effects of doxorubicin and doxorubicin-DNA in patients with acute non-lymphoblastic leukemia. One hundred and twenty consecutive patients within the age range 15 to 60 years were randomized to one of three treatment groups. In two of these, remission induction treatment was performed with prednisolone, vincristine, ara-C and thioguanine combined with either doxorubicin or doxorubicin-DNA. Patients entering a complete remission received intensive consolidation during 16 months with 4 courses each of doxorubicin (+/ - DNA)/ara-C, doxorubicin (+/ - DNA)/azacytidine, ara-C and amsacrine. The third treatment group followed a protocol from a previous study with daunorubicin and ara-C for induction therapy and a less intensive maintenance therapy. No further patients were assigned to this "control" group after 3 years or to the two other groups after 6 years. This report is based on a follow-up 31 months thereafter. The overall rate of complete remission was 67% and the mean time to complete remission was 71 days, with no differences between the treatment groups. Patients treated with the doxorubicin-DNA conjugate had a significantly longer survival [median for all patients 27.2 months (p < 0.01) and for patients in CR 47.0 months (p < 0.025)] and longer duration of first remission (median 23.6 months, p < 0.025) than the other groups. There were significantly fewer reports of cardiotoxicity (p < 0.05) and severe intestinal toxicity (p < 0.02) in patients treated with the doxorubicin-DNA conjugate and there was a tendency towards less hepatic (p < 0.08) and renal toxicity (p < 0.08). The frequency of myelosuppression, fever and infectious complications was similar in all three groups. Complex binding to DNA appears to increase the therapeutic effects and reduce some toxic effects of doxorubicin in patients with ANLL.

Drinking Behavior, Remission, and Relapse: The Rand Report Revisited

Utilizing the Armor, Polich, and Stambul 1976 criteria, the clinical course of patients from 26 treatment programs was studied, with relapse analyses differing from the data reported by Armor et al. The overall rate of remission at 6 mo follow-up was considerably lower (54%) in this study. The data suggest that those alcoholics who chose to reduce their drinking, as an option, experienced a substantial risk of relapse.

Blastic crisis in chronic granulocytic leukemia: experience in 39 patients.

In an attempt to prolong survival, a group of 39 adult patients with chronic granulocytic leukemia in acute transformation was treated with intensive chemotherapy regimens which included the use of single agents or drug combinations. An over-all remission rate of 28% was obtained, with only 10% of the patients achieving complete remission. The cytogenetic profiles obtained during the acute phase of the disease were correlated with the clinical findings and the response to therapy. The results presented in this report indicate that, even with the use of modern therapeutic drugs, once chronic granulocytic leukemia enters a phase of acute transformation, the prognosis is equally poor for both Ph1 negative and Ph1 positive patients.